ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.
A multienzyme complex responsible for the formation of ACETYL COENZYME A from pyruvate. The enzyme components are PYRUVATE DEHYDROGENASE (LIPOAMIDE); dihydrolipoamide acetyltransferase; and LIPOAMIDE DEHYDROGENASE. Pyruvate dehydrogenase complex is subject to three types of control: inhibited by acetyl-CoA and NADH; influenced by the energy state of the cell; and inhibited when a specific serine residue in the pyruvate decarboxylase is phosphorylated by ATP. PYRUVATE DEHYDROGENASE (LIPOAMIDE)-PHOSPHATASE catalyzes reactivation of the complex. (From Concise Encyclopedia Biochemistry and Molecular Biology, 3rd ed)
An intermediate compound in the metabolism of carbohydrates, proteins, and fats. In thiamine deficiency, its oxidation is retarded and it accumulates in the tissues, especially in nervous structures. (From Stedman, 26th ed)
A metabolic process that converts GLUCOSE into two molecules of PYRUVIC ACID through a series of enzymatic reactions. Energy generated by this process is conserved in two molecules of ATP. Glycolysis is the universal catabolic pathway for glucose, free glucose, or glucose derived from complex CARBOHYDRATES, such as GLYCOGEN and STARCH.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
Catalyzes the decarboxylation of an alpha keto acid to an aldehyde and carbon dioxide. Thiamine pyrophosphate is an essential cofactor. In lower organisms, which ferment glucose to ethanol and carbon dioxide, the enzyme irreversibly decarboxylates pyruvate to acetaldehyde. EC 4.1.1.1.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Diphosphoric acid esters of fructose. The fructose-1,6- diphosphate isomer is most prevalent. It is an important intermediate in the glycolysis process.
An allosteric enzyme that regulates glycolysis by catalyzing the transfer of a phosphate group from ATP to fructose-6-phosphate to yield fructose-1,6-bisphosphate. D-tagatose- 6-phosphate and sedoheptulose-7-phosphate also are acceptors. UTP, CTP, and ITP also are donors. In human phosphofructokinase-1, three types of subunits have been identified. They are PHOSPHOFRUCTOKINASE-1, MUSCLE TYPE; PHOSPHOFRUCTOKINASE-1, LIVER TYPE; and PHOSPHOFRUCTOKINASE-1, TYPE C; found in platelets, brain, and other tissues.
The rate dynamics in chemical or physical systems.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
Agents that inhibit PROTEIN KINASES.
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
The E1 component of the multienzyme PYRUVATE DEHYDROGENASE COMPLEX. It is composed of 2 alpha subunits (pyruvate dehydrogenase E1 alpha subunit) and 2 beta subunits (pyruvate dehydrogenase E1 beta subunit).
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
Biosynthesis of GLUCOSE from nonhexose or non-carbohydrate precursors, such as LACTATE; PYRUVATE; ALANINE; and GLYCEROL.
A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.
A ketotriose compound. Its addition to blood preservation solutions results in better maintenance of 2,3-diphosphoglycerate levels during storage. It is readily phosphorylated to dihydroxyacetone phosphate by triokinase in erythrocytes. In combination with naphthoquinones it acts as a sunscreening agent.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
Hemolytic anemia due to various intrinsic defects of the erythrocyte.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
Salts or esters of LACTIC ACID containing the general formula CH3CHOHCOOR.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
Any one of a group of congenital hemolytic anemias in which there is no abnormal hemoglobin or spherocytosis and in which there is a defect of glycolysis in the erythrocyte. Common causes include deficiencies in GLUCOSE-6-PHOSPHATE ISOMERASE; PYRUVATE KINASE; and GLUCOSE-6-PHOSPHATE DEHYDROGENASE.
Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.
A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.
An enzyme that catalyzes the conversion of ATP and a D-hexose to ADP and a D-hexose 6-phosphate. D-Glucose, D-mannose, D-fructose, sorbitol, and D-glucosamine can act as acceptors; ITP and dATP can act as donors. The liver isoenzyme has sometimes been called glucokinase. (From Enzyme Nomenclature, 1992) EC 2.7.1.1.
A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
An enzyme of the lyase class that catalyzes the cleavage of fructose 1,6-biphosphate to form dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. The enzyme also acts on (3S,4R)-ketose 1-phosphates. The yeast and bacterial enzymes are zinc proteins. (Enzyme Nomenclature, 1992) E.C. 4.1.2.13.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A normal intermediate in the fermentation (oxidation, metabolism) of sugar. The concentrated form is used internally to prevent gastrointestinal fermentation. (From Stedman, 26th ed)
A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.
An enzyme catalyzing the transfer of a phosphate group from 3-phospho-D-glycerate in the presence of ATP to yield 3-phospho-D-glyceroyl phosphate and ADP. EC 2.7.2.3.
A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of LACTATE and PYRUVATE. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.
Contractile tissue that produces movement in animals.
(Pyruvate dehydrogenase (lipoamide))-phosphate phosphohydrolase. A mitochondrial enzyme that catalyzes the hydrolytic removal of a phosphate on a specific seryl hydroxyl group of pyruvate dehydrogenase, reactivating the enzyme complex. EC 3.1.3.43.
Derivatives of OXALOACETIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include a 2-keto-1,4-carboxy aliphatic structure.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal GLUCAGON-LIKE PEPTIDES. Glucagon is secreted by PANCREATIC ALPHA CELLS and plays an important role in regulation of BLOOD GLUCOSE concentration, ketone metabolism, and several other biochemical and physiological processes. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1511)
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
A series of oxidative reactions in the breakdown of acetyl units derived from GLUCOSE; FATTY ACIDS; or AMINO ACIDS by means of tricarboxylic acid intermediates. The end products are CARBON DIOXIDE, water, and energy in the form of phosphate bonds.
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Hereditary disorders of pyruvate metabolism. They are difficult to diagnose and describe because pyruvate is a key intermediate in glycolysis, gluconeogenesis, and the tricarboxylic acid cycle. Some inherited metabolic disorders may alter pyruvate metabolism indirectly. Disorders in pyruvate metabolism appear to lead to deficiencies in neurotransmitter synthesis and, consequently, to nervous system disorders.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.
A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.
A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.
The modification of the reactivity of ENZYMES by the binding of effectors to sites (ALLOSTERIC SITES) on the enzymes other than the substrate BINDING SITES.
A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
Allosteric enzymes that regulate glycolysis and gluconeogenesis. These enzymes catalyze phosphorylation of fructose-6-phosphate to either fructose-1,6-bisphosphate (PHOSPHOFRUCTOKINASE-1 reaction), or to fructose-2,6-bisphosphate (PHOSPHOFRUCTOKINASE-2 reaction).
A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.
A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
An enzyme that catalyzes the conversion of D-fructose 1,6-bisphosphate and water to D-fructose 6-phosphate and orthophosphate. EC 3.1.3.11.
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
An enzyme that catalyzes the conversion of (S)-malate and NAD+ to oxaloacetate and NADH. EC 1.1.1.37.
Lengthy and continuous deprivation of food. (Stedman, 25th ed)
An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.
Enzymes that catalyze the dehydrogenation of GLYCERALDEHYDE 3-PHOSPHATE. Several types of glyceraldehyde-3-phosphate-dehydrogenase exist including phosphorylating and non-phosphorylating varieties and ones that transfer hydrogen to NADP and ones that transfer hydrogen to NAD.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.
A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.
A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases IMMUNITY, and provides energy for muscle tissue, BRAIN, and the CENTRAL NERVOUS SYSTEM.
The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
An enzyme of the lyase class that catalyzes the conversion of GTP and oxaloacetate to GDP, phosphoenolpyruvate, and carbon dioxide. This reaction is part of gluconeogenesis in the liver. The enzyme occurs in both the mitochondria and cytosol of mammalian liver. (From Dorland, 27th ed) EC 4.1.1.32.
Established cell cultures that have the potential to propagate indefinitely.
Proteins prepared by recombinant DNA technology.
A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
A group of enzymes that catalyzes the conversion of ATP and D-glucose to ADP and D-glucose 6-phosphate. They are found in invertebrates and microorganisms, and are highly specific for glucose. (Enzyme Nomenclature, 1992) EC 2.7.1.2.
The coenzyme form of Vitamin B1 present in many animal tissues. It is a required intermediate in the PYRUVATE DEHYDROGENASE COMPLEX and the KETOGLUTARATE DEHYDROGENASE COMPLEX.
A monosaccharide in sweet fruits and honey that is soluble in water, alcohol, or ether. It is used as a preservative and an intravenous infusion in parenteral feeding.
An inherited metabolic disorder caused by deficient enzyme activity in the PYRUVATE DEHYDROGENASE COMPLEX, resulting in deficiency of acetyl CoA and reduced synthesis of acetylcholine. Two clinical forms are recognized: neonatal and juvenile. The neonatal form is a relatively common cause of lactic acidosis in the first weeks of life and may also feature an erythematous rash. The juvenile form presents with lactic acidosis, alopecia, intermittent ATAXIA; SEIZURES; and an erythematous rash. (From J Inherit Metab Dis 1996;19(4):452-62) Autosomal recessive and X-linked forms are caused by mutations in the genes for the three different enzyme components of this multisubunit pyruvate dehydrogenase complex. One of the mutations at Xp22.2-p22.1 in the gene for the E1 alpha component of the complex leads to LEIGH DISEASE.
A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
A cell line derived from cultured tumor cells.
Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
A derivative of ACETIC ACID that contains two CHLORINE atoms attached to its methyl group.
An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.
An enzyme that catalyzes the acetyltransferase reaction using ACETYL CoA as an acetyl donor and dihydrolipoamide as acceptor to produce COENZYME A (CoA) and S-acetyldihydrolipoamide. It forms the (E2) subunit of the PYRUVATE DEHYDROGENASE COMPLEX.
Stable carbon atoms that have the same atomic number as the element carbon, but differ in atomic weight. C-13 is a stable carbon isotope.
Inorganic salts of phosphoric acid.
The sum of the weight of all the atoms in a molecule.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
A coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). (Dorland, 27th ed)
Derivatives of ACETIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxymethane structure.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
An enzyme that is found in mitochondria and in the soluble cytoplasm of cells. It catalyzes reversible reactions of a nucleoside triphosphate, e.g., ATP, with a nucleoside diphosphate, e.g., UDP, to form ADP and UTP. Many nucleoside diphosphates can act as acceptor, while many ribo- and deoxyribonucleoside triphosphates can act as donor. EC 2.7.4.6.
Elements of limited time intervals, contributing to particular results or situations.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Cellular processes in biosynthesis (anabolism) and degradation (catabolism) of CARBOHYDRATES.
An enzyme that catalyzes the conversion of ATP and PHOSPHORYLASE B to ADP and PHOSPHORYLASE A.
An ester of glucose with phosphoric acid, made in the course of glucose metabolism by mammalian and other cells. It is a normal constituent of resting muscle and probably is in constant equilibrium with fructose-6-phosphate. (Stedman, 26th ed)
Carbohydrates present in food comprising digestible sugars and starches and indigestible cellulose and other dietary fibers. The former are the major source of energy. The sugars are in beet and cane sugar, fruits, honey, sweet corn, corn syrup, milk and milk products, etc.; the starches are in cereal grains, legumes (FABACEAE), tubers, etc. (From Claudio & Lagua, Nutrition and Diet Therapy Dictionary, 3d ed, p32, p277)
A trace element with atomic symbol Mn, atomic number 25, and atomic weight 54.94. It is concentrated in cell mitochondria, mostly in the pituitary gland, liver, pancreas, kidney, and bone, influences the synthesis of mucopolysaccharides, stimulates hepatic synthesis of cholesterol and fatty acids, and is a cofactor in many enzymes, including arginase and alkaline phosphatase in the liver. (From AMA Drug Evaluations Annual 1992, p2035)
An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.
A dicarboxylic acid ketone that is an important metabolic intermediate of the CITRIC ACID CYCLE. It can be converted to ASPARTIC ACID by ASPARTATE TRANSAMINASE.
Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.
A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
A rather large group of enzymes comprising not only those transferring phosphate but also diphosphate, nucleotidyl residues, and others. These have also been subdivided according to the acceptor group. (From Enzyme Nomenclature, 1992) EC 2.7.
A family of non-receptor, PROLINE-rich protein-tyrosine kinases.
An enzyme with high affinity for carbon dioxide. It catalyzes irreversibly the formation of oxaloacetate from phosphoenolpyruvate and carbon dioxide. This fixation of carbon dioxide in several bacteria and some plants is the first step in the biosynthesis of glucose. EC 4.1.1.31.
The chemical reactions involved in the production and utilization of various forms of energy in cells.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.
An enzyme that catalyzes the reaction of ATP, pyruvate, and orthophosphate to form AMP plus phosphoenolpyruvate plus pyrophosphate. EC 2.7.9.1.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.
An allosteric enzyme that regulates glycolysis and gluconeogenesis by catalyzing the transfer of a phosphate group from ATP to fructose-6-phosphate to yield fructose-2,6-bisphosphate, an allosteric effector for the other 6-phosphofructokinase, PHOSPHOFRUCTOKINASE-1. Phosphofructokinase-2 is bifunctional: the dephosphorylated form is a kinase and the phosphorylated form is a phosphatase that breaks down fructose-2,6-bisphosphate to yield fructose-6-phosphate.
Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
The relationship between the dose of an administered drug and the response of the organism to the drug.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
An oxidative decarboxylation process that converts GLUCOSE-6-PHOSPHATE to D-ribose-5-phosphate via 6-phosphogluconate. The pentose product is used in the biosynthesis of NUCLEIC ACIDS. The generated energy is stored in the form of NADPH. This pathway is prominent in tissues which are active in the synthesis of FATTY ACIDS and STEROIDS.
Compounds or factors that act on a specific enzyme to increase its activity.
A 195-kDa MAP kinase kinase kinase with broad specificity for MAP KINASE KINASES. It is found localized in the CYTOSKELETON and can activate a variety of MAP kinase-dependent pathways.
A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
Enzymes that catalyze the addition of a carboxyl group to a compound (carboxylases) or the removal of a carboxyl group from a compound (decarboxylases). EC 4.1.1.
PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.
Oxidoreductases that are specific for KETONES.
An enzyme that catalyzes the conversion of 2-phospho-D-glycerate to 3-phospho-D-glycerate. EC 5.4.2.1.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.

Functional studies by site-directed mutagenesis on the role of Sp1 in the expression of the pyruvate kinase M and aldolase A genes. (1/1157)

During the cell cycle of mitogen stimulated rat thymocytes, an 8-10-fold induction of glycolytic enzymes and a corresponding increase in the mRNA levels has been observed. This prompted us to study the transcriptional regulation of the rat aldolase A and pyruvate kinase M genes. cis-Regulatory elements of both promoters were evaluated by site-directed mutagenesis of promoter/luciferase constructs and transient transfections of rat hepatoma FTO2B cells. Furthermore, the binding proteins were identified by mobility shift assays in the presence of specific antibodies. In the aldolase AH1 promoter, five binding sites for Sp1 and Sp3 and a TPA responsive element were identified as essential for transcriptional regulation. Most of the promoter activity can be attributed to these regulatory elements. In the pyruvate kinase M promoter three out of five binding sites of Sp1 and Sp3 (B box and GC boxes 1 and 3) turned out to be functional in the transfection assays whereas the disruption of GC box 2 had no effect, and the disruption of the GC box 4 had only a minor effect on the promoter activity. Both promoters are stimulated by Sp1 as well as Sp3, as judged by cotransfection experiments of Drosophila SL2 cells. Therefore, the Sp1- and Sp3-directed transcription provides a means for common regulatory mechanism of the aldolase A and the pyruvate kinase M genes.  (+info)

Activities of glucose metabolic enzymes in human preantral follicles: in vitro modulation by follicle-stimulating hormone, luteinizing hormone, epidermal growth factor, insulin-like growth factor I, and transforming growth factor beta1. (2/1157)

Modulation of glucose metabolic capacity of human preantral follicles in vitro by gonadotropins and intraovarian growth factors was evaluated by monitoring the activities of phosphofructokinase (PFK) and pyruvate kinase (PK), two regulatory enzymes of the glycolytic pathway, and malate dehydrogenase (MDH), a key mitochondrial enzyme of the Krebs cycle. Preantral follicles in classes 1 and 2 from premenopausal women were cultured separately in vitro in the absence or presence of FSH, LH, epidermal growth factor (EGF), insulin-like growth factor (IGF-I), or transforming growth factor beta1 (TGFbeta1) for 24 h. Mitochondrial fraction was separated from the cytosolic fraction, and both fractions were used for enzyme assays. FSH and LH significantly stimulated PFK and PK activities in class 1 and 2 follicles; however, a 170-fold increase in MDH activity was noted for class 2 follicles that were exposed to FSH. Although both EGF and TGFbeta1 stimulated glycolytic and Krebs cycle enzymes for class 1 preantral follicles, TGFbeta1 consistently stimulated the activities of both glycolytic enzymes more than that of EGF. IGF-I induced PK and MDH activities in class 1 follicles but negatively influenced PFK activity for class 1 follicles. In general, only gonadotropins consistently stimulated both glycolytic and Krebs cycle enzyme activities several-fold in class 2 follicles. These results suggest that gonadotropins and ovarian growth factors differentially influence follicular energy-producing capacity from glucose. Moreover, gonadotropins may either directly influence glucose metabolism in class 2 preantral follicles or do so indirectly through factors other than the well-known intraovarian growth factors. Because growth factors modulate granulosa cell mitosis and functionality, their role on energy production may be related to specific cellular activities.  (+info)

Oval cell numbers in human chronic liver diseases are directly related to disease severity. (3/1157)

The risk of developing hepatocellular carcinoma is significantly increased in patients with genetic hemochromatosis, alcoholic liver disease, or chronic hepatitis C infection. The precise mechanisms underlying the development of hepatocellular carcinoma in these conditions are not well understood. Stem cells within the liver, termed oval cells, are involved in the pathogenesis of hepatocellular carcinoma in animal models and may be important in the development of hepatocellular carcinoma in human chronic liver diseases. The aims of this study were to determine whether oval cells could be detected in the liver of patients with genetic hemochromatosis, alcoholic liver disease, or chronic hepatitis C, and whether there is a relationship between the severity of the liver disease and the number of oval cells. Oval cells were detected using histology and immunohistochemistry in liver biopsies from patients with genetic hemochromatosis, alcoholic liver disease, or chronic hepatitis C. Oval cells were not observed in normal liver controls. Oval cell numbers increased significantly with the progression of disease severity from mild to severe in each of the diseases studied. We conclude that oval cells are frequently found in subjects with genetic hemochromatosis, alcoholic liver disease, or chronic hepatitis C. There is an association between severity of liver disease and increase in the number of oval cells consistent with the hypothesis that oval cell proliferation is associated with increased risk for development of hepatocellular carcinoma in chronic liver disease.  (+info)

Homogeneous pyruvate kinase isolated from yeast by two different methods is indistinguishable from pyruvate kinase in cell-free extract. (4/1157)

In this report, we have compared homogeneous yeast (Saccharomyces cerevisiae) pyruvate kinase to enzyme from cell-free extracts in several different ways: 1) isoelectric focusing of cell-free extracts indicates one peak of pyruvate kinase activity whose isoelectric point is the same as that of the pure enzyme; 2) antibody prepared to the pure enzyme produces a single, fused precipitin line against enzyme in the cell-free extract and pure enzyme; 3) immunoelectrophoresis of cell-free extract produces one precipitin arc which has the same mobility as that of the pure enzyme; and 4) immunoprecipitation of the pure enzyme from cell-free extract with subsequent solubilization in 1% sodium dodecyl sulfate and electrophoresis on sodium dodecyl sulfate-polyacrylamide gels produces a single protein band attributable to pyruvate kinase which co-migrates with the purified enzyme. Within the limits of the sensitivity of the methods employed, we conclude that the homogeneous pyruvate kinase prepared from yeast lysed either by Manton-Gaulin homogenization (Aust, A., Yun, S.-L., and Suelter, C. (1975) Methods Enzymol. 42, 176-182) or by toluolysis (Yun, S.-L., Aust, A.E., and Suelter, C.H. (1977) J. Biol. Chem. 251, 124-128) is identical with pyruvate kinase in cell-free extract.  (+info)

Effects of vanadium complexes with organic ligands on glucose metabolism: a comparison study in diabetic rats. (5/1157)

1. Vanadium compounds can mimic actions of insulin through alternative signalling pathways. The effects of three organic vanadium compounds were studied in non-ketotic, streptozotocin-diabetic rats: vanadyl acetylacetonate (VAc), vanadyl 3-ethylacetylacetonate (VEt), and bis(maltolato)oxovanadium (VM). A simple inorganic vanadium salt, vanadyl sulphate (VS) was also studied. 2. Oral administration of the three organic vanadium compounds (125 mg vanadium element 1(-1) in drinking fluids) for up to 3 months induced a faster and larger fall in glycemia (VAc being the most potent) than VS. Glucosuria and tolerance to a glucose load were improved accordingly. 3. Activities and mRNA levels of key glycolytic enzymes (glucokinase and L-type pyruvate kinase) which are suppressed in the diabetic liver, were restored by vanadium treatment. The organic forms showed greater efficacy than VS, especially VAc. 4. VAc rats exhibited the highest levels of plasma or tissue vanadium, most likely due to a greater intestinal absorption. However, VAc retained its potency when given as a single i.p. injection to diabetic rats. Moreover, there was no relationship between plasma or tissue vanadium levels and any parameters of glucose homeostasis and hepatic glucose metabolism. Thus, these data suggest that differences in potency between compounds are due to differences in their insulin-like properties. 5. There was no marked toxicity observed on hepatic or renal function. However, diarrhoea occurred in 50% of rats chronically treated with VS, but not in those receiving the organic compounds. 6. In conclusion, organic vanadium compounds, in particular VAc, correct the hyperglycemia and impaired hepatic glycolysis of diabetic rats more safely and potently than VS. This is not simply due to improved intestinal absorption, indicating more potent insulin-like properties.  (+info)

Changes in mitochondrial phosphorylative activity and adenylate energy charge of regenerating rabbit liver. (6/1157)

The changes in the cellular concentrations of ATP, ADP, and AMP and in oxidative phosphorylation of mitochondria were investigated in the remaining liver of partially hepatectomized rabbits. The energy charge (defined as half of the average number of anhydride-bonded phosphate groups per adenosine moiety) of the liver remnant decreased from 0.866 to 0.767 (p less than 0.01) within 24 hr after hepatectomy, and then increased to a substantially higher level than normal within 7 days. On the other hand, the mitochondrial phosphyorylative activity increased rapidly to 170 per cent of the control within 12 hr and then retruned to normal within 7 days. The mitochondrial phosphorylative activity was inversely correlated with energy charge of the liver remnant (r = -0.75, p less less than 0.01). The maximal enhancement of mitochondrial phosphorylative activity was found in mitochondria obtained from the liver remnant with the lowest level of energy charge, suggesting a response of mitochondria in vivo involving enhanced biosynthetic ATP-utilizing reactions at an early stage of the regenerating process. The enhancement of phosphorylative activity was accompanied by a rise in the respiratory control ratio, P/O ratio and state 3 respiration. The adenylate kinase [EC 2.7.4.3] activity in the liver remnant increased to more than 160% of the control within 2 days after partial hepatectomy, while the pyruvate kinase [EC 2.7.1.40] activity decreased remarkably. However, the changes in the two enzyme activities did not correlate with those of mitochondrial phosphorylative activity or the energy charge of the liver remnant.  (+info)

Studies on the kinetic effects of adenosine-3':5'-monophosphate-dependent phosphorylation of purified pig-liver pyruvate kinase type L. (7/1157)

The effect of cyclic-AMP-dependent phosphorylation on the activity of isolated pig liver pyruvate kinase was studied. It was found that the major kinetic effect of the phosphorylation was to reduce the affinity for the substrate phosphoenolpyruvate, K0.5 for this substrate increasing from 0.3 to 0.9 mM upon phosphorylation. The cooperative effect with phosphoenolpyruvate was enhanced, the Hill constant nH increasing concomitantly from 1.1 to 1.5. V was unaltered. The change in activity occurred in parallel with the phosphate incorporation, except during the initial part of the reaction, when inactivation was correspondingly slower. The affinity for the second substrate ADP was unchanged, with an apparent Km of 0.3 mM at saturating concentration of phosphoenolpyruvate. Likewise, the requirement for potassium was unaffected, whereas the phosphoenzyme required a higher concentration of magnesium ions for maximal activity, compared with the control enzyme. The inhibitory effect of the phosphorylation was counteracted by positive effectors, fructose 1,6-biphosphate in micromolar concentrations completely activated the phosphoenzyme, resulting in an enzyme with properties similar to the fructose 1,6-biphosphate-activated unphosphorylated enzyme, with K0.5 for phosphoenolpyruvate about 0.025 mM and with a Hill constant of 1.1. Hydrogen ions were also effective in activating the phosphoenzyme. Thus, when pH was lowered from 8 to 6.5 the inhibition due to phosphorylation was abolished. The phosphoenzyme was sensitive to further inhibition by negative effectors such as ATP and alanine. 2 mM ATP increased K0.5 for phosphoenolpyruvate to 1.5 mM and nH to 2.3. The corresponding values with alanine were 1.3 mM and 1.9. Phosphorylation is thought to be an additional mechanism of inhibition of the enzyme under gluconeogenetic conditions.  (+info)

Transgenic inhibitors identify two roles for protein kinase A in Drosophila development. (8/1157)

We have initiated an analysis of protein kinase A (PKA) in Drosophila using transgenic techniques to modulate PKA activity in specific tissues during development. We have constructed GAL4/UAS-regulated transgenes in active and mutant forms that encode PKAc, the catalytic subunit of PKA, and PKI(1-31), a competitive inhibitor of PKAc. We present evidence that the wild-type transgenes are active and summarize the phenotypes produced by a number of GAL4 enhancer-detector strains. We compare the effects of transgenes encoding PKI(1-31) with those encoding PKAr*, a mutant regulatory subunit that constitutively inhibits PKAc because of its inability to bind cyclic AMP. Both inhibitors block larval growth, but only PKAr* alters pattern formation by activating the Hedgehog signaling pathway. Therefore, transgenic PKI(1-31) should provide a tool to investigate the role of PKAc in larval growth regulation without concomitant changes in pattern formation. The different effects of PKI(1-31) and PKAr* suggest two distinct roles, cytoplasmic and nuclear, for PKAc in Hedgehog signal transduction. Alternatively, PKAr* may target proteins other than PKAc, suggesting a role for free PKAr in signal transduction, a role inhibited by PKAc in reversal of the classical relationship of these subunits.  (+info)

Article: Metabolic enzyme pyruvate kinase M2 regulates platelet function and arterial thrombosis Authors: Manasa K Nayak, Madankumar Ghatge, Gagan D Flora, Nirav Dhanesha, Manish Jain, Kathleen R Markan, Matthew J Potthoff, Steven R Lentz, Anil K Chauhan Journal: Blood. 2020 Oct 7;blood.2020007140. doi: 10.1182/blood.2020007140. Online ahead of print. Abstract:Very little is known about the role…
Approach and Results-We identified a large number of JmjC domain-containing proteins regulated by endothelial differentiation of murine embryonic stem cells. Among the family of JmjC domain-only proteins, Jmjd8 was significantly upregulated on endothelial differentiation. Knockdown of Jmjd8 in ECs significantly decreased in vitro network formation and sprouting in the spheroid assay. JMJD8 is exclusively detectable in the cytoplasm, excluding a function as a histone-modifying enzyme. Mass spectrometry analysis revealed JMJD8-interacting proteins with known functions in cellular metabolism like pyruvate kinase M2. Accordingly, knockdown of pyruvate kinase M2 in human umbilical vein ECs decreased endothelial sprouting in the spheroid assay. Knockdown of JMJD8 caused a reduction of EC metabolism as measured by Seahorse Bioscience extracellular flux analysis. Conversely, overexpression of JMJD8 enhanced cellular oxygen consumption rate of ECs, reflecting an increased mitochondrial respiration. ...
Urs Giger. Anemia is one of the most common clinical signs and abnormal laboratory test results in companion animals. Although acquired conditions such as infections, immune disorders, intoxications, blood loss and chronic organ failures represent the main causes of anemia, hereditary blood diseases leading to anemia are also important in clinical practice. Several hereditary erythrocyte defects have been reported in cats and a molecular basis of the erythrocyte pyruvate kinase defect has recently been determined.. Pyruvate kinase is a key regulatory enzyme in the metabolism of sugar. Its deficiency leads to a lack of energy production and thus, an instability of erythrocyte blood cells. This will then result in anemia. PK deficient cats typically have intermittent anemia. The age of onset is quite variable and may depend on environmental factors. The youngest affected cat diagnosed with anemia was 6 months of age and the oldest affected cat was 12 years old and was only found based on screening ...
TY - JOUR. T1 - Pyruvate kinase M2. T2 - Multiple faces for conferring benefits on cancer cells. AU - Tamada, Mayumi. AU - Suematsu, Makoto. AU - Saya, Hideyuki. PY - 2012/10/15. Y1 - 2012/10/15. N2 - The M2 splice isoform of pyruvate kinase (PKM2), an enzyme that catalyzes the later step of glycolysis, is a key regulator of aerobic glycolysis (known as the Warburg effect) in cancer cells. Expression and low enzymatic activity of PKM2 confer on cancer cells the glycolytic phenotype, which promotes rapid energy production and flow of glycolytic intermediates into collateral pathways to synthesize nucleic acids, amino acids, and lipids without the accumulation of reactive oxygen species.PKM2 enzymatic activity has also been shown to be negatively regulated by the interaction with CD44 adhesion molecule, which is a cell surface marker for cancer stem cells. In addition to the glycolytic functions, nonglycolytic functions of PKM2 in cancer cells are of particular interest. PKM2 is induced ...
TY - JOUR. T1 - Pyruvate kinase M2. T2 - Multiple faces for conferring benefits on cancer cells. AU - Tamada, Mayumi. AU - Suematsu, Makoto. AU - Saya, Hideyuki. PY - 2012/10/15. Y1 - 2012/10/15. N2 - The M2 splice isoform of pyruvate kinase (PKM2), an enzyme that catalyzes the later step of glycolysis, is a key regulator of aerobic glycolysis (known as the Warburg effect) in cancer cells. Expression and low enzymatic activity of PKM2 confer on cancer cells the glycolytic phenotype, which promotes rapid energy production and flow of glycolytic intermediates into collateral pathways to synthesize nucleic acids, amino acids, and lipids without the accumulation of reactive oxygen species.PKM2 enzymatic activity has also been shown to be negatively regulated by the interaction with CD44 adhesion molecule, which is a cell surface marker for cancer stem cells. In addition to the glycolytic functions, nonglycolytic functions of PKM2 in cancer cells are of particular interest. PKM2 is induced ...
Mitapivat showed positive safety and efficacy outcomes in patients with pyruvate kinase deficiency who were not regularly receiving red cell transfusions.
A deficiency in the enzyme Pyruvate Kinase impairs the red blood cells ability to metabolize, which in turn may cause anemia and other blood-related issues. Breeds more prone to this deficiency include the Abyssinian, Somali, and domestic shorthair cats. Learn more about the causes and treatment of this condition in cats on PetMD.com.
Intact rats trained on a controlled feeding and lighting schedule designated 8+16 exhibited diurnal oscillations in liver weight, glucokinase activity and liver glycogen content. Glucokinase activity expressed as units/g of liver decreased to 30% of that from unoperated controls during the first 48h after partial hepatectomy and returned to near normal values in 2 weeks. When the glucokinase activity was expressed as units/liver per 100g body wt., a decrease to 50% of control activity was observed between 24 and 48h after the operation. A similar pattern was found for pyruvate kinase type I. In contrast, pyruvate kinase type III activity increased after partial hepatectomy. It is suggested that the newly divided cells after partial hepatectomy do not synthesize glucokinase and pyruvate kinase I but do synthesize pyruvate kinase III. Glycogen was found to accumulate as early as 24h after partial hepatectomy, and normal concentrations were reached after 48h if the operation was performed at ...
Pyruvate kinase is the enzyme that catalyzes the final step of glycolysis. It catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to adenosine diphosphate (ADP), yielding one molecule of pyruvate and one molecule of ATP. Pyruvate kinase is present in four distinct, tissue-specific isozymes in animals, each consisting of particular kinetic properties necessary to accommodate the variations in metabolic requirements of diverse tissues. There are four isozymes of pyruvate kinase in vertebrates: L (liver), R (erythrocytes), M1(muscles, hearts and brain) and M2 (only form detectable in early fetal tissue and present in most adult tissues). R and L isozymes differ from M1 and M2 in that they are both exclusively allosterically and reversibly regulated. From a kinetic standpoint, the R and L isozymes of pyruvate kinase have two key conformation states; one with a high substrate affinity and one with a low substrate affinity. The R-state, characterized by high substrate affinity, ...
Macrophages activated by the TLR4 agonist LPS undergo dramatic changes in their metabolic activity. We here show that LPS induces expression of the key metabolic regulator Pyruvate Kinase M2 (PKM2). Activation of PKM2 using two well-characterized small molecules, DASA-58 and TEPP-46, inhibited LPS-induced Hif-1α and IL-1β, as well as the expression of a range of other Hif-1α-dependent genes. Activation of PKM2 attenuated an LPS-induced proinflammatory M1 macrophage phenotype while promoting traits typical of an M2 macrophage. We show that LPS-induced PKM2 enters into a complex with Hif-1α, which can directly bind to the IL-1β promoter, an event that is inhibited by activation of PKM2. Both compounds inhibited LPS-induced glycolytic reprogramming and succinate production. Finally, activation of PKM2 by TEPP-46 in vivo inhibited LPS and Salmonella typhimurium-induced IL-1β production, while boosting production of IL-10. PKM2 is therefore a critical determinant of macrophage activation by ...
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We report the cloning of the pykA and pykF genes from Escherichia coli, which code for the two pyruvate kinase isoenzymes (ATP:pyruvate 2-O-phosphotransferases; EC 2.7.1.40) in this microorganism. These genes were insertionally inactivated with antibiotic resistance markers and utilized to interrupt one or both pyk genes in the E. coli chromosome. With these constructions, we were able to study the role of these isoenzymes in pyruvate biosynthesis. ...
Different pyruvate kinase isoforms are expressed in a tissue-specific manner, with pyruvate kinase M2 (PKM2) suggested to be the predominant isoform in proliferating cells and cancer cells. Due to differential regulation of enzymatic activities, PKM2 but not PKM1 has been thought to favor cell proliferation. However, the role of PKM2 in tumorigenesis has been recently challenged. Here we report that increased glucose catabolism through glycolysis and increased pyruvate kinase activity in c-MYC-driven liver tumors are associated with increased expression of both PKM1 and PKM2 isoforms and decreased expression of the liver-specific isoform of pyruvate kinase, PKL. Depletion of PKM2 at the time of c-MYC over-expression in murine livers did not affect c-MYC induced tumorigenesis and resulted in liver tumor formation with decreased pyruvate kinase activity and decreased catabolism of glucose into alanine and the Krebs cycle. An increased PKM1/PKM2 ratio by ectopic PKM1 expression further decreased ...
Pyruvate kinase (PK) deficiency is a rare hereditary condition that effects red blood cells. Learn more from Boston Childrens Hospital.
What is the subunit composition? Larsen, T. M., L. T. Laughlin, H. M. Holden, L. Rayment, G. H. Reed. 1994. Structure of rabbit muscle pyruvate kinase complexed with Mn2+, K+, and pyruvate. Biochemistry 33:6301-6309.. ...
Abstract: Together with an increase in the total activity of pyruvate kinase, alterations in the isoenzyme spectrum were observed in hepatocarcinogenesis caused by treatment of rats with diethylinitrosamine. The alterations might be divided into two steps: initial, reversible changes and changes immediately related to development of the blastomatous process. The total activity of pyruvate kinase was gradually increased with appearance of hyperplastic symptoms as well as of primary tumoral foci in liver tissue. The M2-type of pyruvate kinase tended to exhibit activation. In primary hepatomas the L-type of the enzyme was decreased and activity of the M2-type was increased ...
Emerging studies have identified microRNAs as possible therapeutic tools for the treatment of glioma, the most aggressive brain tumor. Their important targets in this tumor are not well understood. We recently found that the Notch pathway is a target of microRNA-326. Ectopic expression of microRNA-326 in glioma and glioma stem cells induced their apoptosis and reduced their metabolic activity. Computational target gene prediction revealed pyruvate kinase type M2 (PKM2) as another target of microRNA-326. PKM2 has recently been shown to play a key role in cancer cell metabolism. To investigate whether it might be a functionally important target of miR-326, we used RNA interference to knock down PKM2 expression in glioma cells. Transfection of established glioma and glioma stem cells with PKM2 siRNA reduced their growth, cellular invasion, metabolic activity with decreased ATP and glutathione levels, and activated AMP-activated protein kinase. The cytotoxic effects exhibited by PKM2 knockdown in ...
Although multiple available siRNA design algorithms did not predict any sequences within alternative exon 10 that would mediate robust silencing, we have identified multiple siRNAs that afford potent and specific silencing of the M2 isoform of pyruvate kinase. An inspection of the 10 top performing sequences reveals that the number of mismatches between the M1 and M2 isoforms ranges from 4 to 13. 5 of these 10 sequences contain mismatches at one of the critical central positions 10 or 11, which have been shown to be important in conferring specificity (Wang et al., 2008b). We observed one hot spot: two of the top three siRNAs target consecutive 19-mers (si155 and si156). We also observed one warm spot: three siRNAs work moderately well over a sequence that spans 23 nucleotides (si83, si85, and si87).. Recent analysis of transcriptomes indicates that ,90% of all human genes are expressed as alternatively spliced isoforms (Wang et al., 2008a). The ability to target one isoform of a gene ...
The enzyme activities and isozyme distribution of the three glycolytic regulator enzymes hexokinase, phosphofructokinase and pyruvate kinase were studied in lymphocytes of patients with chronic lymphocytic leukemia. Isozyme distribution patterns were determined by kinetic measurements, electrophoresis and immunoprecipitation. The CLL lymphocytes were different from normal non-T lymphocytes with respect to hexokinase ... read more residual activity in the presence of glucose-1,6-P2, pyruvate kinase residual activity in the presence of alanine, and phosphofructokinase activity after stimulation by glucose-1,6-P2. No differences could be discerned in enzyme activities between the CLL and the normal T and non-T lymphocytes. show less ...
1A5U: Structure of the bis(Mg2+)-ATP-oxalate complex of the rabbit muscle pyruvate kinase at 2.1 A resolution: ATP binding over a barrel.
In contrast to the case in liver and skeletal muscle, the role of AMPK in β-cell functions is less clear. Glucose stimulation of β-cells has been associated with a reduction in the AMP/ATP ratio and decreased AMPK activity (28). Activation of AMPK by 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) at 200 μmol/l was reported to inhibit glucose-stimulated upregulation of liver-type pyruvate kinase (L-PK) promoter activity and pre-proinsulin promoter activity in MIN6 cells (29). Regarding insulin secretion, diverse effects have been observed with 1 mmol/l AICAR; it acutely (within 5 min) enhances 10 mmol/l glucose-stimulated insulin secretion, but inhibits it in the later phase by ∼50% (28). The effect of AICAR on insulin secretion may also be affected by glucose concentrations. Thus, in the presence of 1 mmol/l AICAR, insulin secretion was inhibited by a high glucose concentration, whereas it was enhanced by a low glucose concentration in rat islets (28). The effects of AICAR ...
There were no significant differences in sex, plasma ferritin level, use of pre-transplant chelation therapy, transfusion burden in the 12 months prior to HSCT, adapted EBMT-score, conditioning regimen, relation to donor, graft type, donor-recipient sex combination, or transplant source.. In conclusion, herein we discuss the first global study on the outcome of all patients known to have undergone HSCT in PKD. Since guidelines for HSCT in PKD are lacking, this report may be a helpful first step toward future protocols. Compared to published survival rates for other forms of hereditary anemias, cohorts that are otherwise comparable in age, time period and transplant hospital, the overall survival rate after HSCT in PKD is relatively low.11-13 The present analysis of all 16 PKD patients known to be transplanted to date showed a three-year overall survival of 65%. Significantly better survival was observed for patients transplanted before the age of ten. A negative effect of age on survival is also ...
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To date, very few PKD patients have underwent stem cell transplantation, mainly because of the significant side effects. Its therefore very difficult to draw conclusions on the benefit of this treatment. Dr. Richard Van Wijk, University Medical Center, Utrecht What is a stem cell? A Stem Cell is a primitive, unripe cell within the body…
Lara had two healthy, big litters of kittens and Bertta one litter of three. They have never been sick in their life. They are both screened negatives for HCM and any other heart conditions, they are big, strong, good mothers, wonderful temperaments, they have multiple titles both in FIFE and TICA. Bertta is full adult whited. They were perfect breeding cats and still are perfect pets. And then came this. About 6 weeks ago I had never heard about PK-def, or didin´t know what it really is. Now I know more than I ever wanted ...
Thats really interesting, thanks for posting. Its especially interesting how it can be mistaken for FIP. I dont know if its just because I come into contact with more Bengal owners over time, but it does seem to me that FIP-like symptoms are being reported more regularly and I have been wondering if they are all FIP or not. Tragically it probably doesnt change the outcome for the poor owner but knowledge is vital for future generations ...
The objective of the present work consisted on determining the effects of PTS and Pyk isozymes inactivation on cell physiology, metabolic flux distribution and PEP availability for aromatics biosynthesis. The inactivation of PTS in E. coli abolishes PEP-dependent glucose transport; therefore PYR production from PEP is dependent only on Pyk isozyme activities. In this study, by inactivating each Pyk isozyme in a PTS- glc+ background, strains were generated where the PEP to PYR reaction was dependent only on PykA or PykF activity. These strains were characterized by flux analysis, thus providing the first quantitative description of the metabolic consequences of the sequential elimination of activities catalyzing the PEP to PYR reaction.. The inactivation of PTS in E. coli causes a strong reduction in qGlc and μ, therefore, such mutant strains display a PTS- glc- phenotype. To improve qGlc and μ, strain VH33 has a chromosomal modification that increases its capacity for non PTS-dependent glucose ...
Pyruvate kinase (PK), an important glycolytic enzyme that catalyzes the final step of glycolysis through an irreversible mechanism to produce energy for the cell, contains nine cysteines, some of which are highly reactive and critical for function. This research sought to develop a protocol to measure quantitatively the functionality of PK under different experimental conditions. Using a three stage, consistent procedure, it was possible to analyze the effects of thiol modification by Ellmans Reagent (DTNB) and oxidation by hypochlorous acid (HOCl) on PK activity. Results showed that both DTNB and HOCl inhibited activity at high concentrations, which illustrates that some cysteines are essential for PK to catalyze its reaction. Furthermore, analysis of cysteine labeling with 5-iodoacetamidofluorescein on SDS-PAGE demonstrates that not all cysteines must be modified to see inhibitory effects. Additionally, incubation studies with ATP and fructose-1,6-bisphosphate, known regulators with different binding
Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Human Pyruvate Kinase, Liver And RBC (PK) in samples from serum, plasma, tissue homogenates, cell lysates and other biological fluids with no significant corss-reactivity with analogues from other species ...
Although Agios is involved in some relatively early stage work on pyruvate kinase deficiency -- a genetic disorder that affects red blood cells ability to carry oxygen -- its the companys oncology platform thats most exciting. Specifically, Agios work with IDH mutant inhibitors is what has me, and Wall Street, excited. Normal IDH enzymes help to generate energy for cells by breaking down nutrients; however, mutant IDH creates a molecule that fails to mature and tends to proliferate rapidly. Thus, Agios approach of inhibiting this mutant form of IDH (IDH1 and IDH2) is believed to have anti-cancer effects.. Agios work is so exciting it got the attention of Celgene (NASDAQ:CELG) years ago, with Celgene eventually licensing the rights to IDH2 mutant inhibitor AG-221, and IDH1 mutant inhibitor AG-120. At the American Society of Hematologys annual meeting in December, Agios announced that AG-221 generated an evaluable response in 37% of patients with relapsed or refractory acute myeloid ...
Blocking interaction of the immune checkpoint receptor PD-1 with its ligand PD-L1 is associated with good clinical outcomes in a broad variety of malignancies. High levels of PD-L1 promote tumour growth by restraining CD8+ T-cell responses against tumors. Limiting PD-L1 expression and function is therefore critical for allowing the development of anti-tumour immune responses and effective tumour clearance. PKM2 is also a key player in regulating cancer as well as immune responses. PKM2 catalyzes the final rate-limiting step of glycolysis. Furthermore PKM2 as a dimer translocates to the nucleus, where it stimulates Hif-1α transactivation domain function and recruitment of p300 to the Hif-1α response elements (HRE) of Hif-1α target genes. Here, we provide the first evidence of a role for PKM2 in regulating the expression of PD-L1 on macrophages, dendritic cells (DCs), T cells and tumour cells. LPS-induced expression of PD-L1 in primary macrophages was inhibited by the PKM2 targeting compound TEPP-46.
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Background Accumulating studies show that epithelial-mesenchymal changeover (EMT) plays a part in tumor metastasis. of leptin on breasts cancer tumor cells was examined. Besides a range of pathway inhibitors aswell as RNA disturbance concentrating on pyruvate kinase M2 (PKM2) had been utilized to clarify the root system of leptin-mediated EMT in vitro and in vivo. Outcomes The results showed that leptin marketed breasts cancer tumor cells EMT visibly turned on the PI3K/AKT signaling pathway and upregulated PKM2 appearance. An antibody against the leptin receptor (anti-ObR) as well as the PI3K/AKT signaling pathway inhibitor LY294002 considerably abolished leptin-induced PKM2 appearance and EMT-associated marker appearance. SiRNA targeting PKM2 abolished leptin-induced migration invasion and EMT-associated marker appearance partially. In vivo xenograft tests indicated that RNA disturbance against PKM2 suppressed breasts cancer tumor metastasis and development. Conclusions Our data claim that ...
Background Accumulating studies show that epithelial-mesenchymal changeover (EMT) plays a part in tumor metastasis. of leptin on breasts cancer tumor cells was examined. Besides a range of pathway inhibitors aswell as RNA disturbance concentrating on pyruvate kinase M2 (PKM2) had been utilized to clarify the root system of leptin-mediated EMT in vitro and in vivo. Outcomes The results showed that leptin marketed breasts cancer tumor cells EMT visibly turned on the PI3K/AKT signaling pathway and upregulated PKM2 appearance. An antibody against the leptin receptor (anti-ObR) as well as the PI3K/AKT signaling pathway inhibitor LY294002 considerably abolished leptin-induced PKM2 appearance and EMT-associated marker appearance. SiRNA targeting PKM2 abolished leptin-induced migration invasion and EMT-associated marker appearance partially. In vivo xenograft tests indicated that RNA disturbance against PKM2 suppressed breasts cancer tumor metastasis and development. Conclusions Our data claim that ...
Compounds and uses | Therapeutically active compounds and their methods of use | Crystalline forms of a biphenyl compound | Pyrimidine compounds for the treatment of hepatitis C | Inhibitors of glutaminyl cyclase |
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Deficiencies in the enzyme pyruvate kinase (PK), the key rate-limiting step in the glycolytic metabolic pathway, might protect some humans against infections by Plasmodium falciparum, the main parasite responsible for causing malaria, according to Philippe Gros of McGill University in Montreal, Quebec, Canada, and his collaborators. Mitochondria are absent from red blood cells, a major host target for such parasites. Hence, defects in host glycolysis, while problematic to humans carrying traits affecting this metabolic pathway, also could prove detrimental to P. falciparum parasites within those cells and, thus, could partly protect such individuals against malaria, the Canadian researchers say. Meanwhile, for those individuals who are heterozygous, although the parasites are only partly blocked when invading such cells, protective phagocytosis of parasites is enhanced-making this host situation
G. McDowell, S Gupta, M Dellerba, C Ward, RD Levy, BG Keevil; Plasma Levels of Dimeric Pyruvate Kinase, a Novel Biochemical Marker of Energy Metabolism, in Patients with Chronic Cardiac Failure. Clin Sci (Lond) 1 January 2003; 104 (s48): 15P. doi: https://doi.org/10.1042/cs104015Pa. Download citation file:. ...
In contrast to the case in liver and skeletal muscle, the role of AMPK in β-cell functions is less clear. Glucose stimulation of β-cells has been associated with a reduction in the AMP/ATP ratio and decreased AMPK activity (28). Activation of AMPK by 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) at 200 μmol/l was reported to inhibit glucose-stimulated upregulation of liver-type pyruvate kinase (L-PK) promoter activity and pre-proinsulin promoter activity in MIN6 cells (29). Regarding insulin secretion, diverse effects have been observed with 1 mmol/l AICAR; it acutely (within 5 min) enhances 10 mmol/l glucose-stimulated insulin secretion, but inhibits it in the later phase by ∼50% (28). The effect of AICAR on insulin secretion may also be affected by glucose concentrations. Thus, in the presence of 1 mmol/l AICAR, insulin secretion was inhibited by a high glucose concentration, whereas it was enhanced by a low glucose concentration in rat islets (28). The effects of AICAR ...
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TY - JOUR. T1 - JMJD5 regulates PKM2 nuclear translocation and reprograms HIF-1α-mediated glucose metabolism. AU - Wang, Hung Jung. AU - Hsieh, Ya Ju. AU - Cheng, Wen Chi. AU - Lin, Chun Pu. AU - Lin, Yu Shan. AU - Yang, So Fang. AU - Chen, Chung Ching. AU - Izumiya, Yoshihiro. AU - Yu, Jau Song. AU - Kung, Hsing Jien. AU - Wang, Wen Ching. PY - 2014/1/16. Y1 - 2014/1/16. N2 - JMJD5, a Jumonji C domain-containing dioxygenase, is important for embryonic development and cancer growth. Here, we show that JMJD5 is up-regulated by hypoxia and is crucial for hypoxiainduced cell proliferation. JMJD5 interacts directly with pyruvate kinase muscle isozyme (PKM)2 to modulate metabolic flux in cancer cells. The JMJD5-PKM2 interaction resides at the intersubunit interface region of PKM2, which hinders PKM2 tetramerization and blocks pyruvate kinase activity. This interaction also influences translocation of PKM2 into the nucleus and promotes hypoxiainducible factor (HIF)-1α-mediated transactivation. JMJD5 ...
Tenofovir (TFV), a nucleotide reverse transcriptase inhibitor, requires two phosphorylation steps to form a competitive inhibitor of HIV reverse transcriptase. Adenylate kinase 2 (AK2) has been previously demonstrated to phosphorylate tenofovir to tenofovir-monophosphate, while creatine kinase, muscle (CKM), pyruvate kinase, muscle (PKM) and pyruvate kinase, liver and red blood cell (PKLR) each have been found to phosphorylate tenofovir-monophosphate to the pharmacologically active tenofovir-diphosphate. In the present study, genomic DNA isolated from dried blood spots collected from 505 participants from Bangkok, Thailand; Cape Town, South Africa; and New York City, USA were examined for variants in AK2, CKM, PKM, and PKLR using next-generation sequencing. The bioinformatics tools SIFT and PolyPhen predicted that 19 of the 505 individuals (3.7% frequency) carried variants in at least one kinase that would result in a decrease or loss of enzymatic activity. To functionally test these predictions, AK2
The Inheritance of PK Deficiency leads to a range of Symptoms and Complications, and Prevalence data may be higher due to missed diagnosis.
The major research objective of our laboratory is to understand the biochemical and genetic basis for cell growth regulation by growth factors and hormones. Research from our laboratory has led to the elucidation of a pathway by which growth factors stimulate nutrient uptake and cellular metabolism, leading to increased cell growth and cell survival. Defects in homeostatic control of this signaling network can lead to cancers or to diabetes or metabolic disease. A central node in this network is the enzyme phosphoinositide 3-kinase. In order to explore the in vivo role of this network we are generating mice in which components of the network can be switched on or off to determine their effects on cancers and other diseases References: Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell. 2007 Jun 29;129(7):1261-74. Christofk HR, Vander Heiden MG, Wu N, Asara JM, Cantley LC. Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature. 2008 Mar 13;452(7184):181-6. Christofk HR,
1AQF: Ligand-induced domain movement in pyruvate kinase: structure of the enzyme from rabbit muscle with Mg2+, K+, and L-phospholactate at 2.7 A resolution.
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During pregnancy, many women experience remission of autoimmune diseases like multiple sclerosis and uveitis. Now, scientists have described a biological mechanism responsible for changes in the immune system that helps to explain the remission.. The expression of an enzyme known as pyruvate kinase is reduced in immune cells in pregnant women compared to non-pregnant women, according to Howard R. Petty, Ph.D., biophysicist at the University of Michigan Kellogg Eye Center and Roberto Romero, M.D., of the National Institutes for Health.. The study, which appears online ahead of print in the August issue of the American Journal of Reproductive Immunology, also reports that expression of the enzyme is lower in pregnant women compared to those with pre-eclampsia, a condition with inflammatory components.. The study is significant because the newly discovered mechanism points to a pathway that could be targeted for treatment. It may be possible to design drugs that mildly suppress pyruvate kinase ...
Stress. It affects all of us in a variety of different ways. Some of us more so than others. The important factor though is how to deal with it. For me, I wind down with my favourite tunes and a large bar of galaxy, but for an individual cell, they have a much more sophisticated…
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Mammals have two pyruvate kinase genes, PK-LR (which encodes for pyruvate kinase isozymes L and R) and PK-M (which encodes for ... Because the substrate for pyruvate kinase is a simple phospho-sugar, and the product is an ATP, pyruvate kinase is a possible ... Therefore, pyruvate kinase deficiency can cause chronic nonspherocytic hemolytic anemia (CNSHA). Pyruvate kinase deficiency is ... causing phosphorylation of pyruvate kinase and the inhibition of glycolysis. The M2 isozyme of pyruvate kinase can form ...
"Entrez Gene: PKLR pyruvate kinase, liver and RBC". Beutler E, Baronciani L (1996). "Mutations in pyruvate kinase". Hum. Mutat. ... 1991). "Point mutations in the L-type pyruvate kinase gene of two children with hemolytic anemia caused by pyruvate kinase ... Pyruvate kinase PKLR is an enzyme that in humans is encoded by the PKLR gene. The protein encoded by this gene is a pyruvate ... Kanno H, Fujii H, Hirono A, Miwa S (1991). "cDNA cloning of human R-type pyruvate kinase and identification of a single amino ...
... (also pyruvate dehydrogenase complex kinase, PDC kinase, or PDK; EC 2.7.11.2) is a kinase enzyme ... Pyruvate dehydrogenase kinase is activated by ATP, NADH and acetyl-CoA. It is inhibited by ADP, NAD+, CoA-SH and pyruvate. Each ... Pyruvate dehydrogenase kinase should not be confused with Phosphoinositide-dependent kinase-1, which is also sometimes known as ... "Site specificity of four pyruvate dehydrogenase kinase isoenzymes toward the three phosphorylation sites of human pyruvate ...
... is due to a mutation in the PKLR gene. There are four pyruvate kinase isoenzymes, two of which are ... Pyruvate kinase deficiency is an inherited metabolic disorder of the enzyme pyruvate kinase which affects the survival of red ... "Pyruvate kinase deficiency: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2015-11-11. "Pyruvate kinase ... Pyruvate kinase deficiency happens worldwide, however northern Europe, and Japan have many cases. The prevalence of pyruvate ...
The enzyme [pyruvate kinase]-phosphatase (EC 3.1.3.49) catalyzes the reaction [pyruvate kinase] phosphate + H2O ⇌ {\ ... This enzyme is also called pyruvate kinase phosphatase. Jett MF, Hue L, Hers HG (1981). "Pyruvate kinase phosphatase". FEBS ... pyruvate kinase] + phosphate This enzyme belongs to the family of hydrolases, specifically those acting on phosphoric monoester ... The systematic name of this enzyme class is [ATP:pyruvate 2-O-phosphotransferase]-phosphate phosphohydrolase. ...
... (EC 2.7.11.32, PPDK regulatory protein, pyruvate, phosphate dikinase regulatory protein, ... pyruvate,+phosphate+dikinase)+kinase at the US National Library of Medicine Medical Subject Headings (MeSH) Portal: Biology (EC ... Chastain CJ, Xu W, Parsley K, Sarath G, Hibberd JM, Chollet R (March 2008). "The pyruvate, orthophosphate dikinase regulatory ... Burnell JN, Chastain CJ (June 2006). "Cloning and expression of maize-leaf pyruvate, Pi dikinase regulatory protein gene". ...
... (EC 2.7.11.33, PSRP, PEPS kinase) is an enzyme with systematic name ADP:(pyruvate, water ... pyruvate,+water+dikinase)+kinase at the US National Library of Medicine Medical Subject Headings (MeSH) Portal: Biology (EC 2.7 ... Burnell JN (January 2010). "Cloning and characterization of Escherichia coli DUF299: a bifunctional ADP-dependent kinase--Pi- ... This enzyme catalyses the following chemical reaction ADP + [pyruvate, water dikinase] ⇌ {\displaystyle \rightleftharpoons } ...
It codes for an isozyme of pyruvate dehydrogenase kinase (PDK). Pyruvate dehydrogenase (PDH) is a part of a mitochondrial ... "Site specificity of four pyruvate dehydrogenase kinase isoenzymes toward the three phosphorylation sites of human pyruvate ... "Entrez Gene: PDK1 pyruvate dehydrogenase kinase, isozyme 1". Park J, Li Y, Kim SH, Kong G, Shrestha R, Tran Q, Hong J, Hur GM, ... Hur H, Xuan Y, Kim YB, Lee G, Shim W, Yun J, Ham IH, Han SU (Jan 2013). "Expression of pyruvate dehydrogenase kinase-1 in ...
... also called erythrocyte pyruvate kinase deficiency, is an inherited metabolic disorder of the enzyme pyruvate kinase. In this ... which in a state of pyruvate kinase deficiency rapidly become deficient in ATP and can undergo hemolysis. Therefore, pyruvate ... Ayi K, Min-Oo G, Serghides L, Crockett M, Kirby-Allen M, Quirt I, Gros P, Kain KC (2008). "Pyruvate kinase deficiency and ... a lack of pyruvate kinase slows down the process of glycolysis. This effect is especially devastating in cells that lack ...
Mutations in pyruvate kinase cause deficiency in pyruvate kinase which prevents adequate red blood cell (RBC) glycolysis, ... September 2017). "AG-348 enhances pyruvate kinase activity in red blood cells from patients with pyruvate kinase deficiency". ... Mitapivat is a pyruvate kinase activator. Mitapivat was approved for medical use in the United States in February 2022. ... Mitapivat is indicated for the treatment of hemolytic anemia in adults with pyruvate kinase deficiency. Mitapivat binds to and ...
Stuart, David Ian (1979). X-ray studies on pyruvate kinase. exlibrisgroup.com (PhD thesis). University of Bristol. David Stuart ... working on the structure of the enzyme pyruvate kinase in the laboratory of Hilary Muirhead. Stuart moved to Oxford in 1979 and ...
Christofk HR, Vander Heiden MG, Wu N, Asara JM, Cantley LC (March 2008). "Pyruvate kinase M2 is a phosphotyrosine-binding ... March 2008). "The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth". Nature. 452 (7184 ... This approach was used to characterize the substrate specificity of a large number of protein kinases. The kinase specificity ... March 2004). "The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to ...
Pyruvate dehydrogenase kinase isoform 2 (PDK2) also known as pyruvate dehydrogenase lipoamide kinase isozyme 2, mitochondrial ... "Structure of pyruvate dehydrogenase kinase. Novel folding pattern for a serine protein kinase". The Journal of Biological ... "Site specificity of four pyruvate dehydrogenase kinase isoenzymes toward the three phosphorylation sites of human pyruvate ... protein kinase B)/glycogen synthase kinase-3 signaling pathway via phosphatidylinositol 3-kinase". Journal of Immunology. 163 ( ...
Israelsen; Vander Heiden, M.G. (2015). "Pyruvate kinase: Function, regulation and role in cancer". Seminars in Cell & ... Pyruvate kinase is also found in the nucleoplasm in significant quantities; this enzyme is involved in the final step of ... glycolysis, catalyzing the conversion of phosphoenolpyruvate (PEP) to pyruvate along with the phosphorylation of adenosine ...
It codes for an isozyme of pyruvate dehydrogenase kinase. This gene is a member of the PDK/BCKDK protein kinase family and ... Kwon HS, Huang B, Unterman TG, Harris RA (Apr 2004). "Protein kinase B-alpha inhibits human pyruvate dehydrogenase kinase-4 ... "Site specificity of four pyruvate dehydrogenase kinase isoenzymes toward the three phosphorylation sites of human pyruvate ... Pyruvate dehydrogenase lipoamide kinase isozyme 4, mitochondrial is an enzyme that in humans is encoded by the PDK4 gene. ...
Fell did research on the physical biochemistry of yeast pyruvate kinase. He obtained a position at Oxford Polytechnic as a ... "The preparation and properties of pyruvate kinase from yeast". Biochemical Journal. 139 (3): 665-675. doi:10.1042/bj1390665. ...
... leading to dephosphorylation and re-activation of pyruvate kinase. These controls prevent pyruvate kinase from being active at ... The final step of glycolysis is catalysed by pyruvate kinase to form pyruvate and another ATP. It is regulated by a range of ... During fasting (no glucose available), glucagon activates protein kinase A which phosphorylates pyruvate kinase to inhibit it. ... Pyruvate kinase ADP ATP 2 × Pyruvate 2 × The first five steps of Glycolysis are regarded as the preparatory (or investment) ...
2003). "Interaction between HERC1 and M2-type pyruvate kinase". FEBS Lett. 539 (1-3): 78-84. doi:10.1016/S0014-5793(03)00205-9 ...
The TIM-barrel in pyruvate kinase is 'discontinuous', meaning that more than one segment of the polypeptide is required to form ... An appropriate example is pyruvate kinase (see first figure), a glycolytic enzyme that plays an important role in regulating ... "The crystal structure of Toxoplasma gondii pyruvate kinase 1". PLOS ONE. 5 (9): e12736. Bibcode:2010PLoSO...512736B. doi: ... which is itself a tyrosine kinase. See also: SH3 domain. Zinc finger DNA-binding domain (ZnF_GATA): ZnF_GATA domain-containing ...
Mazurek, S; Grimm H; Boschek CB; Vaupel P; Eigenbrodt E (2002). "Pyruvate kinase type M2: a crossroad in the tumor metabolome ... Eigenbrodt, E; Kallinowski F; Ott M; Mazurek S; Vaupel P (1998). "Pyruvate kinase and the interaction of amino acid and ... role of pyruvate kinase type M2 and the glycolytic enzyme complex". Biochemical Journal. 356 (Pt 1): 247-256. doi:10.1042/0264- ... pyruvate + NAD(P)H + H+ + CO2 pyruvate + NADH + H+ → lactate + NAD+ The reactions of the glutaminolytic pathway take place ...
"Pyruvate kinase M2 is requisite for Th1 and Th17 differentiation". JCI Insight. 4 (12): e127395. doi:10.1172/jci.insight.127395 ... for the increased production of IL-17 by promoting the activity of glutaminase 1 and suppressing the activity of pyruvate ...
Pyruvate kinase isozymes M1/M2 (PKM1/M2), also known as pyruvate kinase muscle isozyme (PKM), pyruvate kinase type K, cytosolic ... Pyruvate kinase catalyzes the last step within glycolysis, the dephosphorylation of phosphoenolpyruvate to pyruvate, and is ... intracellular gonococci bind pyruvate kinase via their Opa proteins and require host pyruvate for growth". Molecular ... "Use of a novel method to find substrates of protein kinase C delta identifies M2 pyruvate kinase". The International Journal of ...
The reaction is similar to the reaction catalysed by pyruvate kinase, which also converts pyruvate to PEP. However, pyruvate ... pyruvate phosphate dikinase, pyruvate-inorganic phosphate dikinase, pyruvate-phosphate dikinase, pyruvate-phosphate ligase, ... In particular, PPDK is very similar to pyruvate kinase, which also catalyses the conversion of pyruvate to phosphoenolpyruvate ... Research has shown that the PPDK binding mechanisms are similar to that of D-Ala-D-Ala ligase and pyruvate kinase. ...
Kaura, B; Bagga, R; Patel, FD (2004). "Evaluation of the Pyruvate Kinase isoenzyme tumor (Tu M2-PK) as a tumor marker for ... Wechsel, HW; Petri, E; Bichler, KH; Feil, G (1999). "Marker for renal cell carcinoma (RCC): The dimeric form of pyruvate kinase ... Hardt, PD; Ngoumou, BK; Rupp, J; Schnell-Kretschmer, H; Kloer, HU (2000). "Tumor M2-pyruvate kinase: A promising tumor marker ... Kumar, Yogesh; Tapuria, Niteen; Kirmani, Naveed; Davidson, Brian R. (2007). "Tumour M2-pyruvate kinase: A gastrointestinal ...
Ibsen, KH; Schiller, KW; Haas, TA (1971). "Interconvertible kinetic and physical forms of human erythrocyte pyruvate kinase". ... 2001). "X-ray structure of HPr kinase: A bacterial protein kinase with a P-loop nucleotide-binding domain". The EMBO Journal. ... "Alanine-mediated reversible inactivation of tumour pyruvate kinase caused by a tetramer-dimer transition". FEBS Letters. 50 (3 ... 2004). "HPr kinase/phosphorylase, a Walker motif A-containing bifunctional sensor enzyme controlling catabolite repression in ...
Phosphoglycerate kinase deficiency affects step 7 of glycolysis. Pyruvate kinase deficiency affects the 10th and last step of ... the pyruvate not converted feeds the citric acid cycle (CAC); both via pyruvate dehydrogenase (PDC, with Acetyl-CoA as ... Note: gluconeogenesis is taking place only in the liver and not in other cells like e.g. muscle cells.) The pyruvate created by ... GeneReviews: Phosphorylase Kinase Deficiency OMIM:GSD 9d OMIM:PRKAG2 Media related to Disorders of carbohydrate metabolism at ...
Feliú JE, Hue L, Hers HG (August 1976). "Hormonal control of pyruvate kinase activity and of gluconeogenesis in isolated ... Glucagon stimulation of PKA also inactivates the glycolytic enzyme pyruvate kinase. In the 1920s, Kimball and Murlin studied ... cAMP-dependent protein kinase). This enzyme, in turn, activates phosphorylase kinase, which then phosphorylates glycogen ... The enzyme protein kinase A that was stimulated by the cascade initiated by glucagon will also phosphorylate a single serine ...
Jeoung NH, Harris RA (October 2010). "Role of pyruvate dehydrogenase kinase 4 in regulation of blood glucose levels". Korean ... Furthermore, not only PEPC-K but brown adipose tissue is also rich in activity of glycerol kinase. Glycerol kinase is the ... Furthermore, by using 1 ATP and bicarbonate, pyruvate will be converted to oxaloacetate. which is catalysed by pyruvate ... When pyruvate or lactate is used as the precursor for glycerol 3-phosphate, glyceroneogenesis follows exactly the same pathway ...
Pyruvate kinase catalyses the ATP-generating step of glycolysis in which phosphoenolpyruvate (PEP) is converted to pyruvate. ... HIF1 then would activate the pyruvate dehydrogenase kinase (PDKs), which inactivate the mitochondrial pyruvate dehydrogenase ... Pyruvate kinase type M2 or PKM2 is present in embryonic, adult stem cells. It is also expressed by many tumor cells. The ... Mazurek S, Boschek CB, Hugo F, Eigenbrodt E (August 2005). "Pyruvate kinase type M2 and its role in tumor growth and spreading ...
Feliú JE, Hue L, Hers HG (August 1976). "Hormonal control of pyruvate kinase activity and of gluconeogenesis in isolated ... cAMP binds to protein kinase A, and the complex phosphorylates phosphorylase kinase. Phosphorylated phosphorylase kinase ... Glucagon stimulation of PKA also inactivates the glycolytic enzyme pyruvate kinase in hepatocytes. Abnormally elevated levels ... cAMP-dependent protein kinase). This enzyme, in turn, activates phosphorylase kinase, which then phosphorylates glycogen ...
... where sugars such as glucose and fructose are converted into pyruvate and some ATP is generated. Pyruvate is an intermediate in ... Binding of the hormone to insulin receptors on cells then activates a cascade of protein kinases that cause the cells to take ... Gluconeogenesis converts pyruvate to glucose-6-phosphate through a series of intermediates, many of which are shared with ... Metabolic reactions may be categorized as catabolic - the breaking down of compounds (for example, of glucose to pyruvate by ...
Lu demonstrated that glycolytic enzyme pyruvate kinase M2 (PKM2) acts as a protein kinase and phosphorylates histone H3 to ... phosphorylates and activates pyruvate dehydrogenase kinase 1 (PDHK1) to repress pyruvate metabolism in mitochondria. Under ... "Metabolic Kinases Moonlighting as Protein Kinases". Trends in Biochemical Sciences. 43 (4): 301-310. doi:10.1016/j.tibs.2018.01 ... In addition to the findings that metabolic enzymes of PKM2, PGK1, KHK-A, and PCK1 can function as protein kinases, he ...
Protein kinases can also be inhibited by competition at the binding sites where the kinases interact with their substrate ... This catabolic pathway consumes glucose and produces ATP, NADH and pyruvate. A key step for the regulation of glycolysis is an ... Hence kinase inhibitors such as imatinib are frequently used to treat malignancies. Janus kinases are another notable example ... A notable class of kinase drug targets is the receptor tyrosine kinases which are essential enzymes that regulate cell growth; ...
... as in glucose-6-phosphate dehydrogenase deficiency and pyruvate kinase deficiency) Paroxysmal nocturnal hemoglobinuria (PNH), ...
Concomitantly, a decrease occurs in the activity of key protein kinase enzyme systems (constituting the PI3kinase/akt/mTOR ... Ward, GR; MacDougall, JD; Sutton, JR; Toews, CJ; Jones, NL (February 1986). "Activation of human muscle pyruvate dehydrogenase ... such as pyruvate dehydrogenase, is decreased by cast immobilization. A similar reduction in the activity of citrate synthase, ... after 9 days of spaceflight in which no reduction in the capacity of skeletal muscle mitochondria to metabolize pyruvate (a ...
... pyruvate - pyruvate oxidation quantum chemistry - quaternary structure radioisotope - radioisotopic labelling - Raman ... ribosomal protein S6 kinase - ribosome - RNA - RNA virus - RNA-binding protein - RNA-directed DNA polymerase - rod outer ... CDC28 protein kinase - cell - cell adhesion molecule - cell biology - cell cycle protein - cell membrane - cell membrane ... kinase - kinesin - kinetic energy - kinetic exclusion assay - kinetics - knock-out mouse - Krebs cycle lactalbumin - lactic ...
... catalyzed by pyruvate kinase, producing pyruvate and ATP. During the preparatory phase, each 6-carbon glucose molecule is ... 1,3-bisphosphoglycerate is then dephosphorylated via phosphoglycerate kinase, producing 3-phosphoglycerate and ATP through a ...
... encoding protein Pyruvate dehydrogenase phosphatase regulatory subunit PKDTS: Polycystic kidney disease, infantile severe, with ... encoding Serine/threonine-protein kinase TAO2 TBC1D24: encoding protein TBC1 domain family, member 24 TEDC2: encoding protein ...
In the last step D-xylulose is phosphorylated by an ATP utilising kinase, XK, to result in D-xylulose-5-phosphate which is an ... The Dahms pathway starts as the Weimberg pathway but the 2-keto-3 deoxy-xylonate is split by an aldolase to pyruvate and ...
Drugs that dilate canaliculi work by inhibiting MLCK or RhoA/Rho-kinase and include diclofenac, bosentan, entacapone, ... February 1995). "Heterogeneity of autoreactive T cell clones specific for the E2 component of the pyruvate dehydrogenase ... the E2 subunit of mitochondrial pyruvate dehydrogenase complex) may be a trigger for PSC. Specifically, PDC-E2 in apoptotic ... These drugs activate the RhoA/Rho-kinase pathway, which inhibits myosin light chain phosphatase (MLCP), and in turn, increases ...
"Selective Phosphorylation Inhibitor of Delta Protein Kinase C-Pyruvate Dehydrogenase Kinase Protein-Protein Interactions: ...
T. litoralis can utilize pyruvate, maltose, and amino acids as energy sources. In a laboratory setting, T. litoralis must be ... litoralis deviates from the common EM pathway is that the modified version contains an ADP dependent hexose kinase and PFK ...
In the citric acid cycle, coenzyme A works as an allosteric regulator in the stimulation of the enzyme pyruvate dehydrogenase. ... CoA is a competitive inhibitor for Pantothenate Kinase, which normally binds ATP. Coenzyme A, three ADP, one monophosphate, and ... Acetyl-CoA is utilised in the post-translational regulation and allosteric regulation of pyruvate dehydrogenase and carboxylase ... and the oxidation of pyruvate in the citric acid cycle. All genomes sequenced to date encode enzymes that use coenzyme A as a ...
... acanthocytes for pyruvate kinase deficiency or McLeod phenotype, sickle cells for sickle cell anemia, spherocytes for immune- ...
... pyruvate 1D-1-guanidino-1-deoxy-3-dehydro-scyllo-inositol + L-alanine Glutamine-scyllo-inositol transaminase (EC 2.6.1.50), an ... phosphate Scyllo-inosamine 4-kinase (EC 2.7.1.65), an enzyme that catalyzes the chemical reaction ATP + 1-amino-1-deoxy-scyllo- ...
Vieille C; Krishnamurthy H; Hyun HH; Savchenko A; Yan H; Zeikus JG (June 2003). "Thermotoga neapolitana adenylate kinase is ... Thermotoga neapolitana is unable to metabolize acetate, lactate, formate, pyruvate, propionate, mannitol, ethanol, methanol, ...
... including creatine kinase. Many drugs may elevate ALT levels, including zileuton, omega-3 acid ethyl esters (Lovaza), anti- ... pyruvate + L-glutamate ALT (and all aminotransferases) require the coenzyme pyridoxal phosphate, which is converted into ... and was formerly called serum glutamate-pyruvate transaminase or serum glutamic-pyruvic transaminase (SGPT) and was first ... the products of this reversible transamination reaction being pyruvate and L-glutamate.[citation needed] L-alanine + α- ...
They are missing the genes for hexokinases, however they have the genes for pyruvate kinases and phosphoenolpyruvate synthase. ...
This is the first reaction of glycolysis, which degrades the sugar to pyruvate. Kinase Phosphorylase Diphosphotransferase [1] ...
"JMJD8 Regulates Angiogenic Sprouting and Cellular Metabolism by Interacting With Pyruvate Kinase M2 in Endothelial Cells". ...
DLAT Pyruvate dehydrogenase phosphatase deficiency; 608782; PDP1 Pyruvate kinase deficiency; 266200; PKLR Rabson-Mendenhall ... SPTA1 Pyruvate carboxylase deficiency; 266150; PC Pyruvate dehydrogenase deficiency; 312170; PDHA1 Pyruvate dehydrogenase E2 ... response to tyrosine kinase inhibitor in; 211980; EGFR Nonsmall cell lung cancer, somatic; 211980; IRF1 Nonsmall cell lung ... response to tyrosine kinase inhibitor in; 211980; EGFR Adenocarcinoma of lung, somatic; 211980; BRAF Adenocarcinoma of lung, ...
... is metabolized in at least three ways: In many animals it is converted to pyruvate via threonine dehydrogenase. An ... In many organisms it is O-phosphorylated by a kinase preparatory to further metabolism. This is especially important in ... In addition, threonine residues undergo phosphorylation through the action of a threonine kinase. In its phosphorylated form, ... aspartokinase β-aspartate semialdehyde dehydrogenase homoserine dehydrogenase homoserine kinase threonine synthase. ...
Kosovar political party Pyruvate kinase, liver-specific This disambiguation page lists articles associated with the title LPK. ...
... results in the insulin-independent induction of several important hepatic lipogenic enzymes including pyruvate kinase, NADP+- ... The glyceraldehyde produced may also be converted to glyceraldehyde 3-phosphate by glyceraldehyde kinase or converted to ... or can be oxidized to pyruvate and reduced to lactate, or be decarboxylated to acetyl CoA in the mitochondria and directed ... Excess dietary fructose can be converted to pyruvate, enter the Krebs cycle and emerges as citrate directed toward free fatty ...
... a polymer Phosphoinositide-dependent kinase Pyruvate dehydrogenase kinase PDK (Namibian music group) This disambiguation page ...
PKA also phosphorylates pyruvate kinase which causes an increase in intracellular levels of fructose 1,6-biphosphate and ... The most important action of PKA in regulating gluconeogenesis is the phosphorylation of phosphorylase kinase which acts to ... protein kinase A (PKA) is activated and phosphorylates the transcription factor cAMP Response Element Binding (CREB) protein. ... decreases intracellular levels of pyruvate, further decreasing glycolytic activity. ...
Pyruvate is oxidized into acetyl coenzyme A catalyzed by pyruvate:ferredoxin oxidoreductase. Two molecules of carbon dioxide ( ... whereas carnivores have butyrate-producing bacterial communities dominated by the butyrate kinase pathway. Butyrate's effects ... This transporter is involved in the concentrative uptake of butyrate and pyruvate produced as a product of fermentation by ... pyruvate and butyrate. ... MCT1 and MCT4 have also been associated with the transport of short chain fatty acids such as ...
Tyrosine kinase (a subclass of protein kinases) is an enzyme that transfers a phosphate group from an ATP molecule to a protein ... "Pyruvate sensitizes pancreatic tumors to hypoxia-activated prodrug TH-302". Cancer & Metabolism. 3 (1): 2. doi:10.1186/s40170- ... Tyrosine kinase Inhibitors block the action of these enzymes. Tyrosine kinase inhibitors have been shown to inhibit the VEGF, ... Tyrosine kinases can contain mutations that cause them to become constitutively active, or stuck in the "on" position, ...
Pyruvate kinase deficiency is an inherited disorder that affects red blood cells, which carry oxygen to the bodys tissues. ... and in red blood cells, where it provides instructions for making an enzyme called pyruvate kinase. The pyruvate kinase enzyme ... medlineplus.gov/genetics/condition/pyruvate-kinase-deficiency/ Pyruvate kinase deficiency. ... Pyruvate kinase deficiency is caused by mutations in the PKLR gene. The PKLR gene is active in the liver. ...
The pyruvate kinase test checks whether you have a pyruvate kinase deficiency, a genetic disorder that reduces the amount of ... Why Is a Pyruvate Kinase Test Ordered?. Pyruvate kinase deficiency is a genetic disorder that is autosomal recessive. This ... Pyruvate Kinase Test. Red blood cells (RBCs) carry oxygen throughout your body. An enzyme known as pyruvate kinase is necessary ... The pyruvate kinase testis a blood test used to measure the levels of pyruvate kinase in your body. ...
Radioisotope studies of bilirubin turnover, ferrokinetics, and red cell survival (51Cr) in a patient with erythrocyte PK deficiency have provided evidence for prompt reticulocyte sequestration and destruction by the reticuloendothelial system. More mature erythrocytes appeared to survive well despite their deficiency of PK. PK-deficient reticulocytes, dependent upon oxidative phosphorylation for ATP production, are exquisitely sensitive to cyanide- or nitrogen-induced mitochondrial inhibition. If oxidative phosphorylation is unavailable, ATP levels decline rapidly, producing alterations in the cell membrane which allow massive losses of potassium and water. The result is a shrunken, spiculated, viscous cell whose rheologic properties would favor its sequestration by the reticuloendothelial system. Those reticulocytes with particularly low levels of PK exhibit very low glycolytic rates and thus are uniquely reliant upon oxidative phosphorylation. Other reticulocytes, better endowed with PK ...
PYRUVATE KINASE ISOZYMES R/L. A, B, C, D. 528. Homo sapiens. Mutation(s): 1 Gene Names: PKLR, PK1, PKL. EC: 2.7.1.40. ... Structure and Function of Human Erythrocyte Pyruvate Kinase. Molecular Basis of Nonspherocytic Hemolytic Anemia.. Valentini, G. ...
... pyruvate kinase] phosphate + H2O = [pyruvate kinase] + phosphate. [EC:3.1.3.49, MetaCyc:PYRUVATE-KINASE-PHOSPHATASE-RXN] ... pyruvate kinase phosphatase activity, pyruvate kinase-phosphatase activity Catalysis of the reaction: [pyruvate kinase] ... Modulation of pyruvate kinase phosphatase activity in hepatocyte extracts by pyruvate kinase-L ligands ... phosphate + H2O = [pyruvate kinase] + phosphate. [EC:3.1.3.49, MetaCyc:PYRUVATE-KINASE-PHOSPHATASE-RXN] ...
Restraining aerobic glycolysis through suppression of pyruvate dehydrogenase kinase (PDHK) is a promising strategy for cancer ... Water-extracted branch of Cinnamomum cassia promotes lung cancer cell apoptosis by inhibiting pyruvate dehydrogenase kinase ... Restraining aerobic glycolysis through suppression of pyruvate dehydrogenase kinase (PDHK) is a promising strategy for cancer ... on the activity of PDHK using both in vitro and cell-based kinase assay were examined in several lung cancer cells. WBCC ...
Pyruvate kinase. Timeline for Protein Pyruvate kinase, N-terminal domain from c.1.12.1: Pyruvate kinase: *Protein Pyruvate ... Family c.1.12.1: Pyruvate kinase [51622] (1 protein). *. Protein Pyruvate kinase, N-terminal domain [51623] (6 species). this ... Protein Pyruvate kinase, N-terminal domain from c.1.12.1: Pyruvate kinase appears in SCOPe 2.07. ... Lineage for Protein: Pyruvate kinase, N-terminal domain. *Root: SCOPe 2.08 *. Class c: Alpha and beta proteins (a/b) [51349] ( ...
Pyruvate kinase deficient hemolytic anemia in an Amish isolate. Am J Hum Genet. 1965; 17:1-8. PubMedGoogle Scholar ... Takegawa S, Fujii H, Miwa S. Change of pyruvate kinase isozymes from M2- to L-type during development of the red cell. Br J ... We constructed a human β-globin (HBB)/human liver and RBC pyruvate kinase (PKLR) hybrid gene for the high level expression of ... Gilsanz F, Vega MA, Gomez-Castillo E, Ruiz-Balda JA, Omenaca F. Fetal anaemia due to pyruvate kinase deficiency. Arch Dis Child ...
G. McDowell, S Gupta, M Dellerba, C Ward, RD Levy, BG Keevil; Plasma Levels of Dimeric Pyruvate Kinase, a Novel Biochemical ... Plasma Levels of Dimeric Pyruvate Kinase, a Novel Biochemical Marker of Energy Metabolism, in Patients with Chronic Cardiac ...
... that the accumulation of two inhibitors of pyruvate kinase could explain the effect of fructose on hepatocyte pyruvate kinase ... Regulation of pyruvate kinase in isolated hepatocytes by metabolites arising from the glycolysis of fructose and other related ... The only regulatory enzyme involved in this conversion is L-type pyruvate kinase. Thus the effects of fructose and other ... The regulation of the intracellular pyruvate kinase was examined by estimating glycolytic flux from the accumulation of lactate ...
PYRUVATE KINASE DEFICIENCY , TIF Issues Charter of Priorities For The Global PKD Patient Community. Moins dune minute ... Accueil/Actualités/PYRUVATE KINASE DEFICIENCY , TIF Issues Charter of Priorities For The Global PKD Patient Community. ... at the support of the broader community of individuals affected by Pyruvate Kinase Deficiency (PKD), TIF went on to issue a PKD ...
The structure and function of pyruvate kinase. Journal Article (Journal Article) Full Text. *Published version (via Digital ... The structure and function of pyruvate kinase. ...
The glycolytic enzyme pyruvate kinase (PK) is required for cancer development, and has been implicated in the metabolic ... Pyruvate kinase is a dosage-dependent regulator of cellular amino acid homeostasis. ... Keywords: cancer metabolism, pyruvate kinase, proteomics, amino acid profile. Received: October 29, 2012, Accepted: October 30 ...
Pyruvate kinase deficiency (PKD) is a rare erythroid metabolic disease caused by mutations in the PKLR gene. Erythrocytes from ... PKDiPSCs were gene edited to integrate a partial codon-optimized R-type pyruvate kinase cDNA in the second intron of the PKLR ... Generation of high number of healthy erythroid cells from gene-edited pyruvate kinase deficiency patient-specific induced ... 2015) Generation of high number of healthy erythroid cells from gene-edited pyruvate kinase deficiency patient-specific induced ...
Described herein are methods for using compounds that activate pyruvate kinase. ... Pyruvate kinase deficiency in patients is confirmed by red blood cell (RBC) pyruvate kinase enzymatic assay. At Week 25, ... of a Pyruvate Kinase-R (PKR) Activator in Subjects with Pyruvate Kinase Deficiency This example describes a Phase 2, open-label ... Activation of Pyruvate Kinase In Vivo Enhances Red Cell Glycolysis in Mice Pyruvate kinase deficiency (PKD) is an autosomal ...
Local ATP production by the plasma membrane-associated glycolytic enzyme pyruvate kinase is essential for the nutrient- ... A) The steady-state Ca2+ response of mouse islets to pyruvate kinase (PK) activator (PKa, 10 μM TEPP-46) shows a primarily one- ... β-cell deletion of the PKm1 and PKm2 isoforms of pyruvate kinase in mice reveals their essential role as nutrient sensors for ... β-cell deletion of the PKm1 and PKm2 isoforms of pyruvate kinase in mice reveals their essential role as nutrient sensors for ...
pyruvate dehydrogenase kinase 2 - PDHK family. Detailed annotation on the structure, function, physiology, pharmacology and ... PDHK family: pyruvate dehydrogenase kinase 2. Last modified on 07/11/2016. Accessed on 26/11/2022. IUPHAR/BPS Guide to ... 2014) VER-246608, a novel pan-isoform ATP competitive inhibitor of pyruvate dehydrogenase kinase, disrupts Warburg metabolism ... CRYSTAL STRUCTURES OF HUMAN PYRUVATE DEHYDROGENASE KINASE 2 CONTAINING PHYSIOLOGICAL AND SYNTHETIC LIGANDS. ...
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Pyruvate kinase deficiency is one of the most common enzymatic defects of the erythrocyte. This disorder manifests clinically ... Clinical spectrum of pyruvate kinase deficiency: data from the Pyruvate Kinase Deficiency Natural History Study. Blood. 2018 ... encoded search term (Pyruvate Kinase Deficiency) and Pyruvate Kinase Deficiency What to Read Next on Medscape ... First-trimester prenatal diagnosis of pyruvate kinase deficiency in an Indian family with the pyruvate kinase-Amish mutation. ...
Genetic testing of the PKLR gene will reliably determine whether a dog is a genetic Carrier of pyruvate kinase deficiency (pug ... Pyruvate kinase deficiency (pug type) is an inherited metabolic disease affecting pugs. Affected dogs have insufficient ... Inal Gultekin G, Raj K, Foureman P, Lehman S, Manhart K, Abdulmalik O, Giger U. Erythrocytic Pyruvate Kinase Mutations Causing ... Pyruvate kinase deficiency (pug type) is inherited in an Autosomal Recessive manner in dogs meaning that they must receive two ...
Pyruvate kinase deficiency (PKD) in cats affects their ability to produce energy from food by breaking down glucose. Understand ... Pyruvate Kinase Deficiency in Cats Pyruvate kinase deficiency in cats is an inherited disorder caused by a mutation in the PK- ... Pyruvate Kinase Deficiency in Cats. By mattMedical Animation, Medical Educational Animation ...
Empowering people with Pyruvate Kinase Deficiency to live a more satisfied life ... Thrive with Pyruvate Kinase Deficiency Organization. Empowering people with Pyruvate Kinase Deficiency to live a more satisfied ... We are a 501(c)(3) nonprofit in the State of Minnesota focused on connecting the Pyruvate Kinase Deficiency community online ...
Download the App Pyruvate Kinase Deficiency - Symptoms, Life Expectancy, Resources If youre a care provider that would like a ... Pyruvate kinase deficiency is a rare genetic disorder. It is caused by DNA changes in the pyruvate kinase gene and leads to ... To make a conclusive diagnosis of pyruvate kinase deficiency, doctors will check the activity of the pyruvate kinase enzyme. ... is a tablet drug that can be used to treat pyruvate kinase deficiency. This drug can bind to, and activate, the pyruvate kinase ...
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During this complication, the placenta activates pyruvate kinase M2 (PKM2), a glycolytic enzyme that plays a significant role ... Regulation of Trophoblast Invasion by Pyruvate Kinase Isozyme M2 (PKM2): Preemptive to PKM2 Activation Decreases IUGR Symptoms ...
Crystal structure of pyruvate dehydrogenase kinase 3 bound to lipoyl domain 2 of human pyruvate dehydrogenase complex. ... Crystal structure of pyruvate dehydrogenase kinase 3 bound to lipoyl domain 2 of human pyruvate dehydrogenase complex. ...
Pyruvate Dehydrogenase Kinase isoenzyme 3. Xp22.11. CMTX6. CMT2. 300906. Inherited focal episodic neuropathies. ... tyrosine kinase; Adapted from [Jonathan Baets, C. Oliver Hanemann, Peter De Jonghe], Inherited Peripheral Neuropathies. ...
... pyruvate kinase; HUS=hemolytic uremic syndrome; TTP=thrombotic thrombocytopenic purpura; DIC=disseminated intravascular ...
... pyruvate kinase; olive green, conserved hypothetical protein; gray, acetyl-CoA carboxylase beta subunit; pink, threonyl-tRNA ... pyruvate dehydrogenase; black, GTP-binding protein lepa; magenta, transcription termination factor rho; brown, yhbG, probable ...
Nucleotide specificity of pyruvate kinase and phosphoenolpyruvate carboxykinase ... While pyruvate kinase shows a rather broad specificity for these analogues, phosphoenolpyruvate carboxykinase has a more ... Nucleotide specificity of pyruvate kinase and phosphoenolpyruvate carboxykinase. From National Research Council Canada ... The biological significance of the different substrate specificities of pyruvate kinase and phosphoenolpyruvate carboxykinase ...
  • and in red blood cells, where it provides instructions for making an enzyme called pyruvate kinase. (medlineplus.gov)
  • The pyruvate kinase enzyme is involved in a critical energy-producing process known as glycolysis. (medlineplus.gov)
  • PKLR gene mutations result in reduced pyruvate kinase enzyme function, causing a shortage of ATP in red blood cells and increased levels of other molecules produced earlier in the glycolysis process. (medlineplus.gov)
  • An enzyme known as pyruvate kinase is necessary for your body to make RBCs and function properly. (healthline.com)
  • Background and Objectives Red blood cell pyruvate kinase (R-PK) deficiency is the most common glycolytic enzyme defect associated with hereditary non-spherocytic hemolytic anemia. (haematologica.org)
  • Pyruvate kinase (PK) deficiency is the most common glycolytic enzyme defect associated with hemolytic anemia. (haematologica.org)
  • The only regulatory enzyme involved in this conversion is L-type pyruvate kinase. (bl.uk)
  • The rapid glycolysis from fructose can be explained by the accumulation of fructose-1,6-bisphosphate and fructose-l-phosphate, causing a stimulation of pyruvate kinase and a depletion of ATP, relieving the inhibition of the enzyme. (bl.uk)
  • The glycolytic enzyme pyruvate kinase (PK) is required for cancer development, and has been implicated in the metabolic transition from oxidative to fermentative metabolism, the Warburg effect. (oncotarget.com)
  • Pyruvate kinase deficiency (PKD) is one of the most common enzyme defects in erythrocytes in humans due to autosomal recessive mutations of the PKLR gene (Zanella, A., et al. (justia.com)
  • In mammals, fully activated pyruvate kinase exists as a tetrameric enzyme. (justia.com)
  • Affected dogs have insufficient activity of the pyruvate kinase Enzyme which breaks down glycogen for energy. (pawprintgenetics.com)
  • Other congenital hemolytic anemias of the nonspherocytic type, hemoglobinopathies, other enzyme deficiencies, and some thalassemic syndromes must also be differentiated from pyruvate kinase deficiency. (medscape.com)
  • During this complication, the placenta activates pyruvate kinase M2 (PKM2), a glycolytic enzyme that plays a significant role in cellular respiration. (byu.edu)
  • TsPKM has two functional domains of pyruvate kinase and the tertiary structure of TsPKM is tetramer which has the enzyme active site constituted by 8 amino- acid residues (Arg71, Asn73, Asp110, Phe241, Lys267, Glu269, Asp293 and Thr325). (bvsalud.org)
  • What enzyme catalyze the formation of pyruvate and from which molecules? (studystack.com)
  • What enzyme catalyze process of conversion of pyruvate to acetyl coA? (studystack.com)
  • Glucose-6-phosphate dehydrogenase deficiency and pyruvate kinase deficiency are the two most common enzyme defects that cause hemolytic anemia. (medscape.com)
  • Aim: To assess G-6-PD, Pyruvate kinase enzyme activity and some coagulation parameters in HIV positive patients on antiretroviral treatment (ART) and those not on antiretroviral treatments with varying durations of infection and Antiretroviral treatments. (who.int)
  • In many instances, patients with pyruvate kinase deficiency will need to undergo blood transfusions to replace damaged RBCs. (healthline.com)
  • Durability of hemoglobin response and reduction in transfusion burden is maintained over time in patients with pyruvate kinase deficiency treated with mitapivat in a long-term extension study. (medscape.com)
  • From a number of research studies by scientists and doctors on pyruvate kinase deficiency, below are lists of symptoms that have been seen in patients with pyruvate kinase deficiency. (lamarhealth.com)
  • Specifically, pyruvate kinase deficiency is a common cause of a type of inherited hemolytic anemia called hereditary nonspherocytic hemolytic anemia. (medlineplus.gov)
  • In people with pyruvate kinase deficiency, hemolytic anemia and associated complications may range from mild to severe. (medlineplus.gov)
  • Pyruvate kinase deficiency is the most common inherited cause of nonspherocytic hemolytic anemia. (medlineplus.gov)
  • Erythrocytes from PKD patients show an energetic imbalance causing chronic non-spherocytic hemolytic anemia, as pyruvate kinase defects impair ATP production in erythrocytes. (gla.ac.uk)
  • In older children, autoimmune hemolytic anemia may also manifest with symptoms that are similar to pyruvate kinase deficiency and, therefore, must be considered in the differential diagnosis. (medscape.com)
  • Structure and Function of Human Erythrocyte Pyruvate Kinase. (rcsb.org)
  • Most people with pyruvate kinase deficiency lead a healthy life. (lamarhealth.com)
  • It is estimated that there are currently 50,000 people with pyruvate kinase deficiency in the United States of America. (lamarhealth.com)
  • Red cell pyruvate kinase deficiency: molecular and clinical aspects. (healthline.com)
  • Abdel Fattah M, Abdel Ghany E, Adel A, Mosallam D, Kamal S. Glucose-6-phosphate dehydrogenase and red cell pyruvate kinase deficiency in neonatal jaundice cases in egypt. (medscape.com)
  • 2014) VER-246608, a novel pan-isoform ATP competitive inhibitor of pyruvate dehydrogenase kinase, disrupts Warburg metabolism and induces context-dependent cytostasis in cancer cells. (guidetopharmacology.org)
  • 3. Morrell JA, Orme J, Butlin RJ, Roche TE, Mayers RM, Kilgour E. (2003) AZD7545 is a selective inhibitor of pyruvate dehydrogenase kinase 2. (guidetopharmacology.org)
  • Futibatinib is a kinase inhibitor of fibroblast growth factor receptor (FGFR) 1, 2, 3, and 4 by covalently binding FGFR. (medscape.com)
  • CHIR-99021 is a glycogen synthase kinase 3 beta inhibitor that has antiproliferative activity in vitro and in vivo. (dcchemicals.com)
  • CHIR-99021 is a GSK-3α/β inhibitor with an IC50 of 10 and 6.7 nM,showing 500-fold selectivity over its closest homologs CDC2 and ERK2, as well as other protein kinases. (dcchemicals.com)
  • PKDiPSCs were gene edited to integrate a partial codon-optimized R-type pyruvate kinase cDNA in the second intron of the PKLR gene by TALEN-mediated homologous recombination (HR). Notably, we found allele specificity of HR led by the presence of a single-nucleotide polymorphism. (gla.ac.uk)
  • Pyruvate kinase deficiency is caused by mutations in the PKLR gene. (medlineplus.gov)
  • Beutler E, Gelbart T. Estimating the prevalence of pyruvate kinase deficiency from the gene frequency in the general white population. (medlineplus.gov)
  • Although the gene is not expressed in either of the parents (meaning that neither has pyruvate kinase deficiency), the recessive trait has a 1-in-4 chance of appearing in any children that the parents have together. (healthline.com)
  • Children born to parents with the pyruvate kinase deficiency gene will be tested for the disorder using the pyruvate kinase test. (healthline.com)
  • Because of these critical functions, pyruvate kinase is tightly controlled at both gene expression and enzymatic allostere levels. (justia.com)
  • Genetic testing of the PKLR gene will reliably determine whether a dog is a genetic Carrier of pyruvate kinase deficiency (pug type). (pawprintgenetics.com)
  • Pyruvate kinase deficiency (pug type) is inherited in an Autosomal Recessive manner in dogs meaning that they must receive two copies of the mutated gene (one from each parent) to develop the disease. (pawprintgenetics.com)
  • Safe and Efficient Gene Therapy for Pyruvate Kinase Deficiency. (medscape.com)
  • Spectrum of novel mutations in the human PKLR gene in pyruvate kinase-deficient Indian patients with heterogeneous clinical phenotypes. (medscape.com)
  • Christensen RD, Yaish HM, Johnson CB, Bianchi P, Zanella A. Six children with pyruvate kinase deficiency from one small town: molecular characterization of the PK-LR gene. (medscape.com)
  • Pyruvate Kinase Deficiency in Cats Pyruvate kinase deficiency in cats is an inherited disorder caused by a mutation in the PK-LR gene. (medical3danimationcompany.com)
  • It is caused by DNA changes in the pyruvate kinase gene and leads to faster than normal breakdown of red blood cells. (lamarhealth.com)
  • Alternative splicing of the pyruvate kinase M gene (PK-M) can generate the M2 isoform and promote aerobic glycolysis and tumor growth. (cshl.edu)
  • In addition to its role of synthesizing one of the two ATP molecules from the metabolism of glucose to pyruvate, pyruvate kinase is also an important cellular metabolism regulator. (justia.com)
  • Characterization of a novel pyruvate kinase from Trichinella spiralis and its participation in sugar metabolism, larval molting and development. (bvsalud.org)
  • The aim of the present study was to evaluate the biological characteristics and roles of T. spiralis pyruvate kinase M (TsPKM) in sugar metabolism , larval molting and development of T. spiralis. (bvsalud.org)
  • cyclic-AMP (cAMP) cascade protein kinase A (PKA). (pdf4pro.com)
  • This low oxygen microenvironment stabilizes hypoxia inducible factors (HIF-1s) and promotes utilization of glycolysis rather than oxidative phosphorylation (OXPHOS) through transcriptional activation of genes that regulate glucose uptake (Glut1) and pyruvate disposal (LDHA and Pdk1). (frontiersin.org)
  • pyruvate kinase, lactate dehydrogenase and glucose-6-phosphate dehydrogenase were investigated. (fluoridealert.org)
  • Glucose-6-phosphate dehydrogenase deficiency affects the pentose phosphate pathway, and pyruvate kinase deficiency affects the glycolytic pathway. (medscape.com)
  • Glucose-6-Phosphate Dehydrogenase (G-6-PD) activity, Pyruvate kinase (PK) activity, Activated Partial Thromboplastin time (APTT), Prothrombin time (PT), Platelet count (PLT)and Human Immunodeficiency virus (HIV) status were determined. (who.int)
  • Before depolarization, pyruvate kinase (PK) lowers ADP, reducing oxidative phosphorylation (OxPhos) and the TCA cycle, which raises acetyl-CoA that allosterically activates pyruvate carboxylase and PEP cataplerosis through phosphoenolpyruvate carboxykinase (PCK2). (elifesciences.org)
  • It was found that the accumulation of two inhibitors of pyruvate kinase could explain the effect of fructose on hepatocyte pyruvate kinase activity. (bl.uk)
  • Other Kinase Inhibitors " has 41 results in Products. (rndsystems.com)
  • Objectives Scientific experience using tyrosine kinase inhibitors (TKIs) in individuals with castration-resistant prostate cancer (CRPC) is normally starting to older. (woofahs.com)
  • Pyruvate kinase deficiency is an inherited disorder that affects red blood cells, which carry oxygen to the body's tissues. (medlineplus.gov)
  • Pyruvate kinase deficiency is a genetic disorder that is autosomal recessive. (healthline.com)
  • Pyruvate Kinase (PK) Deficiency is a disorder that causes anemia due to the breakdown of red blood cells. (wisdompanel.com)
  • Restraining aerobic glycolysis through suppression of pyruvate dehydrogenase kinase (PDHK) is a promising strategy for cancer inhibition. (nih.gov)
  • Moreover, one of the consequences of decreased ATP and pyruvate levels is lowered lactate level leading to inability to regenerate NAD+ through lactate dehydrogenase for further use in glycolysis. (justia.com)
  • Conversion of hyperpolarized [1- 13 C]pyruvate into [1- 13 C]lactate was elevated following acute hypoxia, suggestive of enhanced anaerobic glycolysis. (biorxiv.org)
  • If glycolysis gets past the phosphofructokinase step, then regulation is at the pyruvate kinase step. (pdf4pro.com)
  • Stimulation of pyruvate kinase phosphatase activity by insulin in isolated rat hepatocytes. (semanticscholar.org)
  • While pyruvate kinase shows a rather broad specificity for these analogues, phosphoenolpyruvate carboxykinase has a more stringent requirement for nucleotides, the intact keto and NH groups at C6 and N1 of the pyrimidine ring representing essential sites for the phosphoenolpyruvate carboxykinase substrate interaction. (canada.ca)
  • The biological significance of the different substrate specificities of pyruvate kinase and phosphoenolpyruvate carboxykinase is discussed as a possible metabolic control factor. (canada.ca)
  • Elevated HP pyruvate to lactate conversion was also seen at the one-week timepoint, in concert with an increase in lactate dehydrogenase (LDH) expression. (biorxiv.org)
  • The activities of the two glycolytic enzymes, pyruvate kinase and lactate dehydrogenase were significantly decreased in erythrocytes of fluorotic patients (Table 2). (fluoridealert.org)
  • Pyruvate kinase deficiency (pug type) is an inherited metabolic disease affecting pugs. (pawprintgenetics.com)
  • The inhibition of water-extracted branch of C. cassia (WBCC) on the activity of PDHK using both in vitro and cell-based kinase assay were examined in several lung cancer cells. (nih.gov)
  • Prevalence of pyruvate kinase deficiency among the south Iranian population: quantitative assay and molecular analysis. (medscape.com)
  • The regulation of the intracellular pyruvate kinase was examined by estimating glycolytic flux from the accumulation of lactate and pyruvate. (bl.uk)
  • A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP . (bvsalud.org)
  • A normal osmotic fragility (which has its limitation in the newborn) may help to differentiate pyruvate kinase deficiency from hereditary spherocytosis. (medscape.com)
  • NICE is unable to make a recommendation on mitapivat (Pyrukynd) for treating pyruvate kinase deficiency in adults because Agios did not provide an evidence submission. (bvsalud.org)
  • It can replenish from Pyruvate with the help of pyruvate carboxylase. (studystack.com)
  • An intracellular-signaling kinase that plays a role in regulating APOPTOSIS . (nih.gov)
  • A positive Coombs test result, the presence of spherocytes, and the absence of typical pyruvate kinase ̶ deficient cells on the peripheral blood film examination are the main features that differentiate the conditions. (medscape.com)
  • Neonates with jaundice caused by pyruvate kinase deficiency may respond to phototherapy and, later, follow a mild clinical course. (medscape.com)
  • The glycolytic flux from fructose exceeded that from other substrates despite the inhibition of pyruvate kinase described above. (bl.uk)
  • Various analogues of adenosine 5′-diphosphate with modifications in the heterocyclic base residue were tested as substrates of rabbit muscle pyruvate kinase (ATP:pyruvate 2-0-phosphotransferase, EC. (canada.ca)
  • Among the key pathways are those controlling cell proliferation , which coordinate a response to the cellular environment, with the mTOR kinase as a critical node. (axonmedchem.com)
  • Findings that favor a diagnosis of pyruvate kinase deficiency are a negative Coombs test result, blood group setups, and a peripheral blood film examination that demonstrates no spherocytes but reveals contracted, shrunken, spiculated red cells (echinocytes) of the pyruvate kinase deficiency. (medscape.com)
  • Described herein are methods for using compounds that activate pyruvate kinase. (justia.com)
  • Incubation of isolated hepatocytes with fructose at high concentrations and with glycerol caused an apparent inhibition of pyruvate kinase. (bl.uk)
  • no significant inhibition on 26 other kinases. (dcchemicals.com)
  • Components and Strategies Cells and components Cell lines had been extracted from ATCC (Rockville, MD). The cells had been resuscitated and cultured inside our laboratory for under six months since resuscitation in RPMI 1640 moderate (Bio-Whittaker, Walkersville, MD) supplemented with 10% FCS (Hyclone, Logan, IL10 UT), gentamicin (50 mg/L), sodium pyruvate (1 mM) and nonessential proteins (0.1 mM). (woofahs.com)
  • CHIR 99021 is a small organic molecule that inhibits GSK3α and GSK3β by competing for their ATP-binding sites.In vitro kinase assays reveal that CHIR 99021 specifically inhibits GSK3β (IC50=~5 nM) and GSK3α (IC50=~10 nM), with little effect on other kinases[2]. (dcchemicals.com)