Hexokinase
Glucose-6-Phosphate
Glucokinase
Glucosephosphates
Glucose
Glycolysis
Phosphofructokinase-1
Anemia, Hemolytic, Congenital Nonspherocytic
Isoenzymes
Pyruvate Kinase
Adenosine Triphosphate
Glucosephosphate Dehydrogenase
o-Phthalaldehyde
Glucose-6-Phosphate Isomerase
Voltage-Dependent Anion Channel 1
Hexoses
Mitochondria
Fructose
Carbohydrate Metabolism
Hexosephosphates
Voltage-Dependent Anion Channels
Fructose-Bisphosphate Aldolase
Phosphotransferases
Mechanisms related to [18F]fluorodeoxyglucose uptake of human colon cancers transplanted in nude mice. (1/1190)
[18F]Fluorodeoxyglucose ([18F]FDG), a glucose analogue, has been widely used for tumor imaging. To investigate the mechanisms related to [18F]FDG uptake by tumors, an experiment involving nude mice was performed. METHODS: Human colon cancer cell lines SNU-C2A, SNU-C4 and SNU-C5 were transplanted to nude mice. Using immunohistochemical staining and Western blot, the expression of glucose transporter (Glut) isoforms (Glut-1 through -5) in xenografted tumors was analyzed. For the analysis of messenger ribonucleic acid (mRNA) expression, reverse-transcription polymerase chain reaction and Northern blot were used and the enzyme activity of hexokinase in cancer tissues was measured by continuous spectrophotometric rate determination. RESULTS: [18F]FDG uptake in SNU-C4 and SNU-C5 cells was higher than in normal colon cells. Among these cells and xenografted tumors, SNU-C5 showed the highest level of [18F]FDG uptake, followed by SNU-C4 and SNU-C2A. An immunostaining experiment showed intense staining of Glut-1 in SNU-C5 tumors but somewhat faint staining in SNU-C4. SNU-C5 tumors also showed positive staining with Glut-3, although this was not the case with SNU-C2A and SNU-C4. Western blot analysis showed the expression of Glut-1 and Glut-3 in all tumors. Experiments involving Northern blot analysis and reverse-transcription polymerase chain reaction confirmed the overexpression of Glut-1 mRNA in all tumors, with the highest level in SNU-C5. The level of Glut-3 mRNA was also elevated in SNU-C5 tumors but not in SNU-C2A and SNU-C4. The enzyme activity of hexokinase did not vary among different tumors. CONCLUSION: Gluts, especially Glut-1, are responsible for [18F]FDG uptake in a nude mouse model of colon cancer rather than hexokinase activity. Increased numbers of glucose transporters at the plasma membrane of cancer cells is attributed to an increased level of transcripts of glucose transporter genes and may be a cause of increased [18F]FDG uptake, at least in colon cancer tumors. (+info)Mannose inhibits Arabidopsis germination via a hexokinase-mediated step. (2/1190)
Low concentrations of the glucose (Glc) analog mannose (Man) inhibit germination of Arabidopsis seeds. Man is phosphorylated by hexokinase (HXK), but the absence of germination was not due to ATP or phosphate depletion. The addition of metabolizable sugars reversed the Man-mediated inhibition of germination. Carbohydrate-mediated regulation of gene expression involving a HXK-mediated pathway is known to be activated by Glc, Man, and other monosaccharides. Therefore, we investigated whether Man blocks germination through this system. By testing other Glc analogs, we found that 2-deoxyglucose, which, like Man, is phosphorylated by HXK, also blocked germination; no inhibition was observed with 6-deoxyglucose or 3-O-methylglucose, which are not substrates for HXK. Since these latter two sugars are taken up at a rate similar to that of Man, uptake is unlikely to be involved in the inhibition of germination. Furthermore, we show that mannoheptulose, a specific HXK inhibitor, restores germination of seeds grown in the presence of Man. We conclude that HXK is involved in the Man-mediated repression of germination of Arabidopsis seeds, possibly via energy depletion. (+info)Developmental regulation of genes mediating murine brain glucose uptake. (3/1190)
We examined the molecular mechanisms that mediate the developmental increase in murine whole brain 2-deoxyglucose uptake. Northern and Western blot analyses revealed an age-dependent increase in brain GLUT-1 (endothelial cell and glial) and GLUT-3 (neuronal) membrane-spanning facilitative glucose transporter mRNA and protein concentrations. Nuclear run-on experiments revealed that these developmental changes in GLUT-1 and -3 were regulated posttranscriptionally. In contrast, the mRNA and protein levels of the mitochondrially bound glucose phosphorylating hexokinase I enzyme were unaltered. However, hexokinase I enzyme activity increased in an age-dependent manner suggestive of a posttranslational modification that is necessary for enzymatic activation. Together, the postnatal increase in GLUT-1 and -3 concentrations and hexokinase I enzymatic activity led to a parallel increase in murine brain 2-deoxyglucose uptake. Whereas the molecular mechanisms regulating the increase in the three different gene products may vary, the age-dependent increase of all three constituents appears essential for meeting the increasing demand of the maturing brain to fuel the processes of cellular growth, differentiation, and neurotransmission. (+info)Glucose metabolism in Neurospora is altered by heat shock and by disruption of HSP30. (4/1190)
We compared the metabolism of [1-13C]glucose by wild type cells of Neurospora crassa at normal growth temperature and at heat shock temperatures, using nuclear magnetic resonance analysis of cell extracts. High temperature led to increased incorporation of 13C into trehalose, relative to all other metabolites, and there was undetectable synthesis of glycerol, which was a prominent metabolite of glucose at normal temperature (30 degrees C). Heat shock strongly reduced formation of tricarboxylic acid cycle intermediates, approximately 10-fold, and mannitol synthesis was severely depressed at 46 degrees C, but only moderately reduced at 45 degrees C. A mutant strain of N. crassa that lacks the small alpha-crystallin-related heat shock protein, Hsp30, shows poor survival during heat shock on a nutrient medium with restricted glucose. An analysis of glucose metabolism of this strain showed that, unlike the wild type strain, Hsp30-deficient cells may accumulate unphosphorylated glucose at high temperature. This suggestion that glucose-phosphorylating hexokinase activity might be depressed in mutant cells led us to compare hexokinase activity in the two strains at high temperature. Hexokinase was reduced more than 35% in the mutant cell extracts, relative to wild type extracts. alpha-Crystallin and an Hsp30-enriched preparation protected purified hexokinase from thermal inactivation in vitro, supporting the proposal that Hsp30 may directly stabilize hexokinase in vivo during heat shock. (+info)Metabolic regulation, activity state, and intracellular binding of glucokinase in insulin-secreting cells. (5/1190)
Regulation of glucose-induced insulin secretion is crucially dependent on glucokinase function in pancreatic beta-cells. Glucokinase mRNA expression was metabolically regulated allowing continuous translation into enzyme protein. Glucokinase enzyme activity in the beta-cell was exclusively regulated by glucose. Using a selective permeabilization technique, different intracellular activity states of the glucokinase enzyme in bioengineered glucokinase-overexpressing RINm5F tissue culture cells were observed. These results could be confirmed in analogous experiments with dispersed islet cells. A diffusible glucokinase fraction with high enzyme activity could be distinguished from an intracellularly bound fraction with low activity. Glucose induced a significant long-term increase of the active glucokinase fraction. This effect was accomplished through the release of glucokinase enzyme protein from an intracellular binding site of protein character. The inhibitory function of this protein factor was abolished through proteolytic digestion or heat inactivation. Northern blot analyses revealed that this binding protein was not identical to the well-known liver glucokinase regulatory protein. This hitherto unknown new protein factor may have the function of a glucokinase regulatory protein in the pancreatic beta-cell, which may regulate glucokinase enzyme activity in a glucose-dependent manner. (+info)Mutations that confer resistance to 2-deoxyglucose reduce the specific activity of hexokinase from Myxococcus xanthus. (6/1190)
The glucose analog 2-deoxyglucose (2dGlc) inhibits the growth and multicellular development of Myxococcus xanthus. Mutants of M. xanthus resistant to 2dGlc, designated hex mutants, arise at a low spontaneous frequency. Expression of the Escherichia coli glk (glucokinase) gene in M. xanthus hex mutants restores 2dGlc sensitivity, suggesting that these mutants arise upon the loss of a soluble hexokinase function that phosphorylates 2dGlc to form the toxic intermediate, 2-deoxyglucose-6-phosphate. Enzyme assays of M. xanthus extracts reveal a soluble hexokinase (ATP:D-hexose-6-phosphotransferase; EC 2.7.1.1) activity but no phosphotransferase system activities. The hex mutants have lower levels of hexokinase activities than the wild type, and the levels of hexokinase activity exhibited by the hex mutants are inversely correlated with the ability of 2dGlc to inhibit their growth and sporulation. Both 2dGlc and N-acetylglucosamine act as inhibitors of glucose turnover by the M. xanthus hexokinase in vitro, consistent with the finding that glucose and N-acetylglucosamine can antagonize the toxic effects of 2dGlc in vivo. (+info)Novel alleles of yeast hexokinase PII with distinct effects on catalytic activity and catabolite repression of SUC2. (7/1190)
In the yeast Saccharomyces cerevisiae, glucose or fructose represses the expression of a large number of genes. The phosphorylation of glucose or fructose is catalysed by hexokinase PI (Hxk1), hexokinase PII (Hxk2) and a specific glucokinase (Glk1). The authors have shown previously that either Hxk1 or Hxk2 is sufficient for a rapid, sugar-induced disappearance of catabolite-repressible mRNAs (short-term catabolite repression). Hxk2 is specifically required and sufficient for long-term glucose repression and either Hxk1 or Hxk2 is sufficient for long-term repression by fructose. Mutants lacking the TPS1 gene, which encodes trehalose 6-phosphate synthase, can not grow on glucose or fructose. In this study, suppressor mutations of the growth defect of a tps1delta hxk1delta double mutant on fructose were isolated and identified as novel HXK2 alleles. All six alleles studied have single amino acid substitutions. The mutations affected glucose and fructose phosphorylation to a different extent, indicating that Hxk2 binds glucose and fructose via distinct mechanisms. The mutations conferred different effects on long- and short-term repression. Two of the mutants showed very similar defects in catabolite repression, despite large differences in residual sugar-phosphorylation activity. The data show that the long- and short-term phases of catabolite repression can be dissected using different hexokinase mutations. The lack of correlation between in vitro catalytic hexokinase activity, in vivo sugar phosphate accumulation and the establishment of catabolite repression suggests that the production of sugar phosphate is not the sole role of hexokinase in repression. Using the set of six hxk2 mutants it was shown that there is a good correlation between the glucose-induced cAMP signal and in vivo hexokinase activity. There was no correlation between the cAMP signal and the short- or long-term repression of SUC2, arguing against an involvement of cAMP in either stage of catabolite repression. (+info)Viscoelastic properties of f-actin, microtubules, f-actin/alpha-actinin, and f-actin/hexokinase determined in microliter volumes with a novel nondestructive method. (8/1190)
A nondestructive method to determine viscoelastic properties of gels and fluids involves an oscillating glass fiber serving as a sensor for the viscosity of the surrounding fluid. Extremely small displacements (typically 1-100 nm) are caused by the glass rod oscillating at its resonance frequency. These displacements are analyzed using a phase-sensitive acoustic microscope. Alterations of the elastic modulus of a fluid or gel change the propagation speed of a longitudinal acoustic wave. The system allows to study quantities as small as 10 microliters with temporal resolution >1 Hz. For 2-100 microM f-actin gels a final viscosity of 1.3-9.4 mPa s and a final elastic modulus of 2.229-2.254 GPa (corresponding to 1493-1501 m/s sound velocity) have been determined. For 10- to 100-microM microtubule gels (native, without stabilization by taxol), a final viscosity of 1.5-124 mPa s and a final elastic modulus of 2.288-2. 547 GPa (approximately 1513-1596 m/s) have been determined. During polymerization the sound velocity in low-concentration actin solutions increased up to +1.3 m/s (approximately 1.69 kPa) and decreased up to -7 m/s (approximately 49 kPa) at high actin concentrations. On polymerization of tubulin a concentration-dependent decrease of sound velocity was observed, too (+48 to -12 m/s approximately 2.3-0.1 MPa, for 10- to 100-microM tubulin). This decrease was interpreted by a nematic phase transition of the actin filaments and microtubules with increasing concentration. 2 mM ATP (when compared to 0.2 mM ATP) increased polymerization rate, final viscosity and elastic modulus of f-actin (17 microM). The actin-binding glycolytic enzyme hexokinase also accelerated the polymerization rate and final viscosity but elastic modulus (2.26 GPa) was less than for f-actin polymerized in presence of 0.2 mM ATP (2.28 GPa). (+info)Hexokinase is an enzyme that plays a crucial role in the initial step of glucose metabolism, which is the phosphorylation of glucose to form glucose-6-phosphate. This reaction is the first step in most glucose catabolic pathways, including glycolysis, pentose phosphate pathway, and glycogen synthesis.
Hexokinase has a high affinity for glucose, meaning it can bind and phosphorylate glucose even at low concentrations. This property makes hexokinase an important regulator of glucose metabolism in cells. There are four isoforms of hexokinase (I-IV) found in different tissues, with hexokinase IV (also known as glucokinase) being primarily expressed in the liver and pancreas.
In summary, hexokinase is a vital enzyme involved in glucose metabolism, catalyzing the conversion of glucose to glucose-6-phosphate, and playing a crucial role in regulating cellular energy homeostasis.
Glucose-6-phosphate (G6P) is a vital intermediate compound in the metabolism of glucose, which is a simple sugar that serves as a primary source of energy for living organisms. G6P plays a critical role in both glycolysis and gluconeogenesis pathways, contributing to the regulation of blood glucose levels and energy production within cells.
In biochemistry, glucose-6-phosphate is defined as:
A hexose sugar phosphate ester formed by the phosphorylation of glucose at the 6th carbon atom by ATP in a reaction catalyzed by the enzyme hexokinase or glucokinase. This reaction is the first step in both glycolysis and glucose storage (glycogen synthesis) processes, ensuring that glucose can be effectively utilized for energy production or stored for later use.
G6P serves as a crucial metabolic branch point, leading to various pathways such as:
1. Glycolysis: In the presence of sufficient ATP and NAD+ levels, G6P is further metabolized through glycolysis to generate pyruvate, which enters the citric acid cycle for additional energy production in the form of ATP, NADH, and FADH2.
2. Gluconeogenesis: During periods of low blood glucose levels, G6P can be synthesized back into glucose through the gluconeogenesis pathway, primarily occurring in the liver and kidneys. This process helps maintain stable blood glucose concentrations and provides energy to cells when dietary intake is insufficient.
3. Pentose phosphate pathway (PPP): A portion of G6P can be shunted into the PPP, an alternative metabolic route that generates NADPH, ribose-5-phosphate for nucleotide synthesis, and erythrose-4-phosphate for aromatic amino acid production. The PPP is essential in maintaining redox balance within cells and supporting biosynthetic processes.
Overall, glucose-6-phosphate plays a critical role as a central metabolic intermediate, connecting various pathways to regulate energy homeostasis, redox balance, and biosynthesis in response to cellular demands and environmental cues.
Glucokinase is an enzyme that plays a crucial role in regulating glucose metabolism. It is primarily found in the liver, pancreas, and brain. In the pancreas, glucokinase helps to trigger the release of insulin in response to rising blood glucose levels. In the liver, it plays a key role in controlling glucose storage and production.
Glucokinase has a unique property among hexokinases (enzymes that phosphorylate six-carbon sugars) in that it is not inhibited by its product, glucose-6-phosphate. This allows it to continue functioning even when glucose levels are high, making it an important regulator of glucose metabolism.
Defects in the gene that codes for glucokinase can lead to several types of inherited diabetes and other metabolic disorders.
Glucose phosphates are organic compounds that result from the reaction of glucose (a simple sugar) with phosphate groups. These compounds play a crucial role in various metabolic processes, particularly in energy metabolism within cells. The addition of phosphate groups to glucose makes it more reactive and enables it to undergo further reactions that lead to the formation of important molecules such as adenosine triphosphate (ATP), which is a primary source of energy for cellular functions.
One notable example of a glucose phosphate is glucose 1-phosphate, which is an intermediate in several metabolic pathways, including glycogenesis (the process of forming glycogen, a storage form of glucose) and glycolysis (the breakdown of glucose to release energy). Another example is glucose 6-phosphate, which is a key regulator of carbohydrate metabolism and serves as an important intermediate in the pentose phosphate pathway, a metabolic route that generates reducing equivalents (NADPH) and ribose sugars for nucleotide synthesis.
In summary, glucose phosphates are essential compounds in cellular metabolism, facilitating energy production, storage, and utilization.
Glucose is a simple monosaccharide (or single sugar) that serves as the primary source of energy for living organisms. It's a fundamental molecule in biology, often referred to as "dextrose" or "grape sugar." Glucose has the molecular formula C6H12O6 and is vital to the functioning of cells, especially those in the brain and nervous system.
In the body, glucose is derived from the digestion of carbohydrates in food, and it's transported around the body via the bloodstream to cells where it can be used for energy. Cells convert glucose into a usable form through a process called cellular respiration, which involves a series of metabolic reactions that generate adenosine triphosphate (ATP)—the main currency of energy in cells.
Glucose is also stored in the liver and muscles as glycogen, a polysaccharide (multiple sugar) that can be broken down back into glucose when needed for energy between meals or during physical activity. Maintaining appropriate blood glucose levels is crucial for overall health, and imbalances can lead to conditions such as diabetes mellitus.
Glycolysis is a fundamental metabolic pathway that occurs in the cytoplasm of cells, consisting of a series of biochemical reactions. It's the process by which a six-carbon glucose molecule is broken down into two three-carbon pyruvate molecules. This process generates a net gain of two ATP molecules (the main energy currency in cells), two NADH molecules, and two water molecules.
Glycolysis can be divided into two stages: the preparatory phase (or 'energy investment' phase) and the payoff phase (or 'energy generation' phase). During the preparatory phase, glucose is phosphorylated twice to form glucose-6-phosphate and then converted to fructose-1,6-bisphosphate. These reactions consume two ATP molecules but set up the subsequent breakdown of fructose-1,6-bisphosphate into triose phosphates in the payoff phase. In this second stage, each triose phosphate is further oxidized and degraded to produce one pyruvate molecule, one NADH molecule, and one ATP molecule through substrate-level phosphorylation.
Glycolysis does not require oxygen to proceed; thus, it can occur under both aerobic (with oxygen) and anaerobic (without oxygen) conditions. In the absence of oxygen, the pyruvate produced during glycolysis is further metabolized through fermentation pathways such as lactic acid fermentation or alcohol fermentation to regenerate NAD+, which is necessary for glycolysis to continue.
In summary, glycolysis is a crucial process in cellular energy metabolism, allowing cells to convert glucose into ATP and other essential molecules while also serving as a starting point for various other biochemical pathways.
Phosphofructokinase-1 (PFK-1) is a rate-limiting enzyme in the glycolytic pathway, which is the metabolic pathway that converts glucose into pyruvate, producing ATP and NADH as energy currency for the cell. PFK-1 plays a crucial role in regulating the rate of glycolysis by catalyzing the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate, using ATP as the phosphate donor.
PFK-1 is allosterically regulated by various metabolites, such as AMP, ADP, and ATP, which act as positive or negative effectors of the enzyme's activity. For example, an increase in the intracellular concentration of AMP or ADP can activate PFK-1, promoting glycolysis and energy production, while an increase in ATP levels can inhibit the enzyme's activity, conserving glucose for use under conditions of low energy demand.
Deficiencies in PFK-1 can lead to a rare genetic disorder called Tarui's disease or glycogen storage disease type VII, which is characterized by exercise intolerance, muscle cramps, and myoglobinuria (the presence of myoglobin in the urine due to muscle damage).
Hemolytic anemia, congenital nonspherocytic is a rare type of inherited anemia characterized by the premature destruction (hemolysis) of red blood cells. This condition is caused by defects in enzymes or proteins that help maintain the structural integrity and function of red blood cells.
In this form of hemolytic anemia, the red blood cells are not spherical in shape like spherocytes; instead, they may be oval or elongated. The most common types of congenital nonspherocytic hemolytic anemia are caused by deficiencies in enzymes such as glucose-6-phosphate dehydrogenase (G6PD) and pyruvate kinase.
Symptoms of this condition may include fatigue, weakness, pale skin, jaundice, dark urine, and an enlarged spleen. Treatment may involve blood transfusions, medications to manage symptoms, and avoidance of certain triggers that can exacerbate the hemolysis. In some cases, a bone marrow transplant may be considered as a curative treatment option.
Isoenzymes, also known as isoforms, are multiple forms of an enzyme that catalyze the same chemical reaction but differ in their amino acid sequence, structure, and/or kinetic properties. They are encoded by different genes or alternative splicing of the same gene. Isoenzymes can be found in various tissues and organs, and they play a crucial role in biological processes such as metabolism, detoxification, and cell signaling. Measurement of isoenzyme levels in body fluids (such as blood) can provide valuable diagnostic information for certain medical conditions, including tissue damage, inflammation, and various diseases.
Pyruvate kinase is an enzyme that plays a crucial role in the final step of glycolysis, a process by which glucose is broken down to produce energy in the form of ATP (adenosine triphosphate). Specifically, pyruvate kinase catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to adenosine diphosphate (ADP), resulting in the formation of pyruvate and ATP.
There are several isoforms of pyruvate kinase found in different tissues, including the liver, muscle, and brain. The type found in red blood cells is known as PK-RBC or PK-M2. Deficiencies in pyruvate kinase can lead to a genetic disorder called pyruvate kinase deficiency, which can result in hemolytic anemia due to the premature destruction of red blood cells.
Adenosine Triphosphate (ATP) is a high-energy molecule that stores and transports energy within cells. It is the main source of energy for most cellular processes, including muscle contraction, nerve impulse transmission, and protein synthesis. ATP is composed of a base (adenine), a sugar (ribose), and three phosphate groups. The bonds between these phosphate groups contain a significant amount of energy, which can be released when the bond between the second and third phosphate group is broken, resulting in the formation of adenosine diphosphate (ADP) and inorganic phosphate. This process is known as hydrolysis and can be catalyzed by various enzymes to drive a wide range of cellular functions. ATP can also be regenerated from ADP through various metabolic pathways, such as oxidative phosphorylation or substrate-level phosphorylation, allowing for the continuous supply of energy to cells.
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), also known as Glucosephosphate Dehydrogenase, is an enzyme that plays a crucial role in cellular metabolism, particularly in the glycolytic pathway. It catalyzes the conversion of glyceraldehyde 3-phosphate (G3P) to 1,3-bisphosphoglycerate (1,3-BPG), while also converting nicotinamide adenine dinucleotide (NAD+) to its reduced form NADH. This reaction is essential for the production of energy in the form of adenosine triphosphate (ATP) during cellular respiration. GAPDH has been widely used as a housekeeping gene in molecular biology research due to its consistent expression across various tissues and cells, although recent studies have shown that its expression can vary under certain conditions.
O-Phthalaldehyde (OPA) is not typically defined in a medical context as it is primarily used in laboratory settings as a reagent for protein quantification and detection. However, it can be mentioned in some scientific or technical medical literature. Here's the general definition:
O-Phthalaldehyde (OPA) is an organic compound with the formula C8H6O2. It is a white to off-white crystalline powder, soluble in most organic solvents and sparingly soluble in water. OPA is primarily used as a fluorescent labeling reagent for primary amines, such as the side chains of lysine residues in proteins. This reaction is commonly used for protein detection and quantification assays, including enzyme-linked immunosorbent assays (ELISAs) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). It is crucial to handle OPA with care due to its potential health hazards, which include skin and eye irritation, respiratory issues, and possible carcinogenicity.
Glucose-6-phosphate isomerase (GPI) is an enzyme involved in the glycolytic and gluconeogenesis pathways. It catalyzes the interconversion of glucose-6-phosphate (G6P) and fructose-6-phosphate (F6P), which are key metabolic intermediates in these pathways. This reaction is a reversible step that helps maintain the balance between the breakdown and synthesis of glucose in the cell.
In glycolysis, GPI converts G6P to F6P, which subsequently gets converted to fructose-1,6-bisphosphate (F1,6BP) by the enzyme phosphofructokinase-1 (PFK-1). In gluconeogenesis, the reaction is reversed, and F6P is converted back to G6P.
Deficiency or dysfunction of Glucose-6-phosphate isomerase can lead to various metabolic disorders, such as glycogen storage diseases and hereditary motor neuropathies.
In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."
1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.
2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.
3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.
4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).
Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.
Voltage-Dependent Anion Channel 1 (VDAC1) is a protein channel found in the outer mitochondrial membrane. It plays a crucial role in the regulation of metabolite and ion exchange between the cytosol and the mitochondria. VDAC1 is voltage-dependent, meaning that its permeability to anions (negatively charged ions) changes based on the electrical potential across the membrane. This channel is also known as the mitochondrial porin. Its dysfunction has been implicated in various pathological conditions, including neurodegenerative diseases and cancer.
Hexoses are simple sugars (monosaccharides) that contain six carbon atoms. The most common hexoses include glucose, fructose, and galactose. These sugars play important roles in various biological processes, such as serving as energy sources or forming complex carbohydrates like starch and cellulose. Hexoses are essential for the structure and function of living organisms, including humans.
Mitochondria are specialized structures located inside cells that convert the energy from food into ATP (adenosine triphosphate), which is the primary form of energy used by cells. They are often referred to as the "powerhouses" of the cell because they generate most of the cell's supply of chemical energy. Mitochondria are also involved in various other cellular processes, such as signaling, differentiation, and apoptosis (programmed cell death).
Mitochondria have their own DNA, known as mitochondrial DNA (mtDNA), which is inherited maternally. This means that mtDNA is passed down from the mother to her offspring through the egg cells. Mitochondrial dysfunction has been linked to a variety of diseases and conditions, including neurodegenerative disorders, diabetes, and aging.
Deoxyglucose is a glucose molecule that has had one oxygen atom removed, resulting in the absence of a hydroxyl group (-OH) at the 2' position of the carbon chain. It is used in research and medical settings as a metabolic tracer to study glucose uptake and metabolism in cells and organisms.
Deoxyglucose can be taken up by cells through glucose transporters, but it cannot be further metabolized by glycolysis or other glucose-utilizing pathways. This leads to the accumulation of deoxyglucose within the cell, which can interfere with normal cellular processes and cause toxicity in high concentrations.
In medical research, deoxyglucose is sometimes labeled with radioactive isotopes such as carbon-14 or fluorine-18 to create radiolabeled deoxyglucose (FDG), which can be used in positron emission tomography (PET) scans to visualize and measure glucose uptake in tissues. This technique is commonly used in cancer imaging, as tumors often have increased glucose metabolism compared to normal tissue.
Mannoheptulose is a type of sugar that occurs naturally in some plants, including avocados and a few other fruits. Its chemical formula is C7H14O7, and it's a heptose (a monosaccharide or simple sugar with seven carbon atoms) with a mannose configuration.
In the context of medical definitions, mannoheptulose might be mentioned in relation to certain metabolic disorders or dietary considerations. For instance, some research has suggested that mannoheptulose may have an impact on insulin secretion and glucose metabolism, although its effects are not fully understood and it is not widely used in clinical practice.
It's worth noting that while mannoheptulose does occur naturally in some foods, it's not a common or well-known sugar, and it's not typically included as an added ingredient in processed foods. As with any sugar or sweetener, it's generally a good idea to consume it in moderation as part of a balanced diet.
Fructose is a simple monosaccharide, also known as "fruit sugar." It is a naturally occurring carbohydrate that is found in fruits, vegetables, and honey. Fructose has the chemical formula C6H12O6 and is a hexose, or six-carbon sugar.
Fructose is absorbed directly into the bloodstream during digestion and is metabolized primarily in the liver. It is sweeter than other sugars such as glucose and sucrose (table sugar), which makes it a popular sweetener in many processed foods and beverages. However, consuming large amounts of fructose can have negative health effects, including increasing the risk of obesity, diabetes, and heart disease.
Carbohydrate metabolism is the process by which the body breaks down carbohydrates into glucose, which is then used for energy or stored in the liver and muscles as glycogen. This process involves several enzymes and chemical reactions that convert carbohydrates from food into glucose, fructose, or galactose, which are then absorbed into the bloodstream and transported to cells throughout the body.
The hormones insulin and glucagon regulate carbohydrate metabolism by controlling the uptake and storage of glucose in cells. Insulin is released from the pancreas when blood sugar levels are high, such as after a meal, and promotes the uptake and storage of glucose in cells. Glucagon, on the other hand, is released when blood sugar levels are low and signals the liver to convert stored glycogen back into glucose and release it into the bloodstream.
Disorders of carbohydrate metabolism can result from genetic defects or acquired conditions that affect the enzymes or hormones involved in this process. Examples include diabetes, hypoglycemia, and galactosemia. Proper management of these disorders typically involves dietary modifications, medication, and regular monitoring of blood sugar levels.
Hexose phosphates are organic compounds that consist of a hexose sugar molecule (a monosaccharide containing six carbon atoms, such as glucose or fructose) that has been phosphorylated, meaning that a phosphate group has been added to it. This process is typically facilitated by enzymes called kinases, which transfer a phosphate group from a donor molecule (usually ATP) to the sugar molecule.
Hexose phosphates play important roles in various metabolic pathways, including glycolysis, gluconeogenesis, and the pentose phosphate pathway. For example, glucose-6-phosphate is a key intermediate in both glycolysis and gluconeogenesis, while fructose-6-phosphate and fructose-1,6-bisphosphate are important intermediates in glycolysis. The pentose phosphate pathway, which is involved in the production of NADPH and ribose-5-phosphate, begins with the conversion of glucose-6-phosphate to 6-phosphogluconolactone by the enzyme glucose-6-phosphate dehydrogenase.
Overall, hexose phosphates are important metabolic intermediates that help regulate energy production and utilization in cells.
Voltage-Dependent Anion Channels (VDACs) are large protein channels found in the outer mitochondrial membrane. They play a crucial role in the regulation of metabolite and ion exchange between the cytosol and the mitochondria. VDACs are permeable to anions such as chloride, phosphate, and bicarbonate ions, as well as to small molecules and metabolites like ATP, ADP, NADH, and others.
The voltage-dependent property of these channels arises from the fact that their permeability can be modulated by changes in the membrane potential across the outer mitochondrial membrane. At low membrane potentials, VDACs are predominantly open and facilitate the flow of metabolites and ions. However, as the membrane potential becomes more positive, VDACs can transition to a closed or partially closed state, which restricts ion and metabolite movement.
VDACs have been implicated in various cellular processes, including apoptosis, calcium homeostasis, and energy metabolism. Dysregulation of VDAC function has been associated with several pathological conditions, such as neurodegenerative diseases, cancer, and ischemia-reperfusion injury.
Fructose-bisphosphate aldolase is a crucial enzyme in the glycolytic pathway, which is a metabolic process that breaks down glucose to produce energy. This enzyme catalyzes the conversion of fructose-1,6-bisphosphate into two triose sugars: dihydroxyacetone phosphate and glyceraldehyde-3-phosphate.
There are two main types of aldolase isoenzymes in humans, classified as aldolase A (or muscle type) and aldolase B (or liver type). Fructose-bisphosphate aldolase refers specifically to aldolase A, which is primarily found in the muscles, brain, and red blood cells. Aldolase B, on the other hand, is predominantly found in the liver, kidney, and small intestine.
Deficiency or dysfunction of fructose-bisphosphate aldolase can lead to metabolic disorders, such as hereditary fructose intolerance, which results from a deficiency in another enzyme called aldolase B. However, it is essential to note that the term "fructose-bisphosphate aldolase" typically refers to aldolase A and not aldolase B.
Phosphotransferases are a group of enzymes that catalyze the transfer of a phosphate group from a donor molecule to an acceptor molecule. This reaction is essential for various cellular processes, including energy metabolism, signal transduction, and biosynthesis.
The systematic name for this group of enzymes is phosphotransferase, which is derived from the general reaction they catalyze: D-donor + A-acceptor = D-donor minus phosphate + A-phosphate. The donor molecule can be a variety of compounds, such as ATP or a phosphorylated protein, while the acceptor molecule is typically a compound that becomes phosphorylated during the reaction.
Phosphotransferases are classified into several subgroups based on the type of donor and acceptor molecules they act upon. For example, kinases are a subgroup of phosphotransferases that transfer a phosphate group from ATP to a protein or other organic compound. Phosphatases, another subgroup, remove phosphate groups from molecules by transferring them to water.
Overall, phosphotransferases play a critical role in regulating many cellular functions and are important targets for drug development in various diseases, including cancer and neurological disorders.
Hemolytic anemia, congenital is a type of anemia that is present at birth and characterized by the abnormal breakdown (hemolysis) of red blood cells. This can occur due to various genetic defects that affect the structure or function of the red blood cells, making them more susceptible to damage and destruction.
There are several types of congenital hemolytic anemias, including:
1. Congenital spherocytosis: A condition caused by mutations in genes that affect the shape and stability of red blood cells, leading to the formation of abnormally shaped and fragile cells that are prone to hemolysis.
2. G6PD deficiency: A genetic disorder that affects the enzyme glucose-6-phosphate dehydrogenase (G6PD), which is essential for protecting red blood cells from damage. People with this condition have low levels of G6PD, making their red blood cells more susceptible to hemolysis when exposed to certain triggers such as infections or certain medications.
3. Hereditary elliptocytosis: A condition caused by mutations in genes that affect the structure and flexibility of red blood cells, leading to the formation of abnormally shaped and fragile cells that are prone to hemolysis.
4. Pyruvate kinase deficiency: A rare genetic disorder that affects an enzyme called pyruvate kinase, which is essential for the production of energy in red blood cells. People with this condition have low levels of pyruvate kinase, leading to the formation of fragile and abnormally shaped red blood cells that are prone to hemolysis.
Symptoms of congenital hemolytic anemia can vary depending on the severity of the condition but may include fatigue, weakness, pale skin, jaundice, dark urine, and an enlarged spleen. Treatment may involve blood transfusions, medications to manage symptoms, and in some cases, surgery to remove the spleen.
Hexokinase
Hexokinase deficiency
Phosphorylation
List of hematologic conditions
Glucokinase
Alberto Sols
HK3
Sidney Colowick
Irwin Rose
Gordon Hammes
List of OMIM disorder codes
Insulin
HKDC1
Kinase
Mannokinase
Glucosamine kinase
Glycolysis
Polyol pathway
Fructolysis
Polyphosphate-glucose phosphotransferase
Robert K. Crane
TP53-inducible glycolysis and apoptosis regulator
List of biochemists
Arsenic poisoning
Athel Cornish-Bowden
HK2
HK1
Michaelis-Menten kinetics
Tameka A. Clemons
Blood sugar level
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GCK gene: MedlinePlus Genetics
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Congenital Hyperinsulinism: Background, Pathophysiology, Etiology
Glucokinase5
- Hexokinases should not be confused with glucokinase, which is a specific hexokinase found in the liver. (wikipedia.org)
- All hexokinases are capable of phosphorylating several hexoses but hexokinase IV(D) is often misleadingly called glucokinase, though it is no more specific for glucose than the other mammalian isoenzymes. (wikipedia.org)
- Mammalian hexokinase IV, also referred to as glucokinase, differs from other hexokinases in kinetics and functions. (wikipedia.org)
- Glucokinase (hexokinase D) is a monomeric cytoplasmic enzyme found in the liver and pancreas that serves to regulate glucose levels in these organs. (raiseupwa.com)
- Glucokinase is among four members from the hexokinase category of enzymes. (pkc-inhibitor.com)
Glycolysis4
- Hexokinase I, the pacemaker of glycolysis in brain tissue, is composed of two structurally similar halves connected by an alpha-helix. (rcsb.org)
- Hexokinase is the initial enzyme of glycolysis, catalyzing the phosphorylation of glucose by ATP to glucose-6-P. It is one of the rate-limiting enzymes of glycolysis. (raiseupwa.com)
- Hexokinase, the enzyme catalyzing the first step of glycolysis, is inhibited by its product, glucose 6-phosphate. (raiseupwa.com)
- In the liver, the first committed step is not hexokinase beacuse just converting to G-6P, though it traps glucose in the cell, does not determine which pathway it will go down (glycolysis or glycogen synthesis). (raiseupwa.com)
Phosphorylation1
- Therefore, we inferred there was regulation of hexokinase activity through phosphorylation, in addition to its regulation at the transcriptional level during early pregnancy. (biomedcentral.com)
Enzyme hexokinase3
- Nonspherocytic hemolytic anemia due to hexokinase deficiency has been shown to be caused by mutations in the HK1 gene , which cause at least a partial deficiency of the enzyme hexokinase. (raiseupwa.com)
- The decrease of glycolytic enzyme hexokinase 1 accelerates tumor malignancy via deregulating energy metabolism but sensitizes cancer cells to 2-deoxyglucose. (oncotarget.com)
- To investigate whether attenuated glycolytic activity modulates tumor progression, the effects of silencing the first and rate-limiting glycolytic enzyme hexokinase (HK) isozymes HK1 and HK2 were examined. (oncotarget.com)
Enzymes1
- It has been reported that lung cancer cells exhibit upregulated expression of all key glycolytic enzymes [hexokinase 2 (HK2), phosphofructokinase and pyruvate kinase (PK)] ( 13 ), suggesting that the essential enzymes of the aerobic glycolytic pathway have a critical role in the development of lung carcinoma. (spandidos-publications.com)
Assay Kit1
- Magnetic Luminex Assay Kit for Hexokinase 2 (HK2) ,etc. (uscnk.com)
Isoenzymes3
- Several hexokinase isoenzymes that provide different functions can occur in a single species. (wikipedia.org)
- Hexokinases I, II, and III are referred to as low-Km isoenzymes because of a high affinity for glucose (below 1 mM). (wikipedia.org)
- Hexokinase II (HKII) is one of 4 mammalian Hexokinase isoenzymes catalyzing the first obligatory step of glucose metabolism. (fu-berlin.de)
HKII2
- Klassischerweise gehört die Hexokinase II (HKII) zu den vier Hexokinase Isoenzymen, die den ersten obligatorischen Schritt im Glukosestoffwechsel von Säugetieren katalysieren. (fu-berlin.de)
- Hexokinase II (HKII) is the predominant hexokinase isozyme expressed in insulin-responsive tissues. (ox.ac.uk)
Irreversibly phosphorylates1
- A hexokinase is an enzyme that irreversibly phosphorylates hexoses (six-carbon sugars), forming hexose phosphate. (wikipedia.org)
Allosterically inhibited2
- Hexokinase IV is monomeric, about 50kDa, displays positive cooperativity with glucose, and is not allosterically inhibited by its product, glucose-6-phosphate. (wikipedia.org)
- These hexokinases are allosterically inhibited by their own product, G-6P. (raiseupwa.com)
Regulation1
- Scholars@Duke publication: Glucose sensing by MondoA:Mlx complexes: a role for hexokinases and direct regulation of thioredoxin-interacting protein expression. (duke.edu)
Mammalian2
- There are four important mammalian hexokinase isozymes (EC 2.7.1.1) that vary in subcellular locations and kinetics with respect to different substrates and conditions, and physiological function. (wikipedia.org)
- Hexokinase I/A is found in all mammalian tissues, and is considered a "housekeeping enzyme," unaffected by most physiological, hormonal, and metabolic changes. (wikipedia.org)
Humans1
- Genes that encode hexokinase have been discovered in every domain of life, and exist among a variety of species that range from bacteria, yeast, and plants to humans and other vertebrates. (wikipedia.org)
Isoenzyme1
- Hexokinase II/B constitutes the principal regulated isoenzyme in many cell types and is increased in many cancers. (wikipedia.org)
Glycolytic1
- Hexokinases phosphorylate glucose to produce glucose-6-phosphate, thus committing glucose to the glycolytic pathway. (thermofisher.com)
Protein1
- No changes of GLUT4 protein and hexokinase activity were detected after 6 h of hyperinsulinemia in either skeletal muscle or adipose tissue. (diabetesjournals.org)
Kinetics2
- Hexokinases I and II follow Michaelis-Menten kinetics at physiological concentrations of substrates. (wikipedia.org)
- Kinetics and Inhibition of Hexokinase Hexokinase activates glycoloysis by phosphorylating glucose. (raiseupwa.com)
Tissues1
- Tissues where hexokinase is present use glucose at low blood serum levels. (raiseupwa.com)
Blood glucose levels2
- Hexokinase IV's activity is mostly regulated by blood glucose levels themselves. (raiseupwa.com)
- Labelled blood samples were collected into coagulant tubes and then sent to the clinical laboratory to measure fasting blood glucose levels using a routine hexokinase method. (who.int)
NADP1
- A highly specific method for determining the concentration of glucose in serum or plasma by spectrophotometrically measuring the NADP formed from hexokinase-catalyzed transformations of glucose and various intermediates. (raiseupwa.com)
Warburg1
- In contrast, mechanism-driven co-targeting hexokinase 2 (HK2)-mediated Warburg effect with 2-deoxyglucose (2-DG) and ULK1-dependent autophagy with chloroquine (CQ) selectively kills cancer cells through intrinsic apoptosis to cause tumor regression in xenograft, leads to a near-complete tumor suppression and remarkably extends survival in Pten. (umn.edu)
Ischemic1
- In the state of ischemic tolerance Hexokinase II is upregulated by Hypoxia inducible factor 1 (HIF-1). (fu-berlin.de)
Contrast2
- In contrast, hexokinase activity increased by two- to eightfold in skeletal muscle and adipose tissue. (diabetesjournals.org)
- In contrast to other forms of hexokinase, this enzyme is not inhibited by its product glucose-6-phosphate but remains active while glucose is abundant. (thermofisher.com)
Colorimetric1
- In addition, hexokinase 2 (HK2) activity was assessed using a colorimetric assay. (biomedcentral.com)
Gene1
- The gene is called hexokinase 1 (HK1). (medindia.net)
Liver1
- Hexokinase IV is present in the liver, pancreas, hypothalamus, small intestine, and perhaps certain other neuroendocrine cells, and plays an important regulatory role in carbohydrate metabolism. (wikipedia.org)
Inhibits2
- What inhibits hexokinase? (raiseupwa.com)
- G6P inhibits hexokinase by binding to the N-terminal domain(this is simple feedback inhibition). (raiseupwa.com)
Mitochondria1
- Hexokinase II is also located at the mitochondria outer membrane so it can have direct access to ATP. (wikipedia.org)
Substrate3
- In most organisms, glucose is the most important substrate for hexokinases, and glucose-6-phosphate is the most important product. (wikipedia.org)
- Hexokinase possesses the ability to transfer an inorganic phosphate group from ATP to a substrate. (wikipedia.org)
- Hexokinase III/C is substrate-inhibited by glucose at physiological concentrations. (wikipedia.org)
Method3
- What is hexokinase method? (raiseupwa.com)
- Glucose concentration was determined by a hexokinase method. (cdc.gov)
- The method also applies to beans and to the animal digestive contents because it involves the hexokinase system for the final glucose determination. (iso.org)
Cellular1
- Hexokinase cellular trafficking in respo. (bezmialem.edu.tr)
Concentration1
- Whenever the concentration of glucose6-phosphate in the cell rises above its normal level, hexokinase is temporarily and reversibly inhibited, bringing the rate of glucose-6phosphate formation into balance with the rate of its utilization and reestablishing the steady state. (raiseupwa.com)
Muscle2
- It is the hexokinase found in muscle and heart. (wikipedia.org)
- The GLUT4 glucose transporter and type II hexokinase are predominantly expressed in skeletal muscle and adipose tissue. (diabetesjournals.org)
Activity4
- The relative specific activity of hexokinase II increases with pH at least in a pH range from 6.9 to 8.5. (wikipedia.org)
- Furthermore, nuclear localization of MondoA:Mlx depends on the enzymatic activity of hexokinases. (duke.edu)
- hexokinase transcript abundance and enzyme activity were significantly higher during diestrus and pregnancy than estrus and anestrus. (biomedcentral.com)
- In addition, despite similar relative transcript abundance, hexokinase activity was significantly greater in the pregnant versus diestrous endometrium. (biomedcentral.com)
Origin1
- This suggests an evolutionary origin by duplication and fusion of a 50kDa ancestral hexokinase similar to those of bacteria. (wikipedia.org)
Active2
- Each consists of two similar 50kDa halves, but only in hexokinase II do both halves have functional active sites. (wikipedia.org)
- Is hexokinase active when phosphorylated? (raiseupwa.com)
Names1
- The alternative names hexokinases I, II, III, and IV (respectively) proposed later are widely used. (wikipedia.org)
Transfer1
- Hexokinase is the enzyme that catalyzes this phosphoryl group transfer. (raiseupwa.com)
Step2
- Why is hexokinase not the committed step? (raiseupwa.com)
- Is hexokinase a committed step? (raiseupwa.com)
Plants1
- Multicellular organisms including plants and animals often have more than one hexokinase isoform. (wikipedia.org)
High1
- The mutant hexokinases bind both glucose 6-phosphate and glucose with high affinity to their N and C-terminal halves, and ADP, also with high affinity, to a site near the N terminus of the polypeptide chain. (rcsb.org)