Ketoglutarate Dehydrogenase Complex
Pyruvate Dehydrogenase Complex
Ketoglutaric Acids
Dihydrolipoamide Dehydrogenase
Dihydrolipoyllysine-Residue Acetyltransferase
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
Keto Acids
Pyruvate Dehydrogenase (Lipoamide)
Pyruvate Dehydrogenase Complex Deficiency Disease
UDPglucose-Hexose-1-Phosphate Uridylyltransferase
Transaminases
Saccharopine Dehydrogenases
Oxaloacetates
Coenzyme A
Thioctic Acid
Glutarates
Thiamine Pyrophosphate
L-Lactate Dehydrogenase
PII Nitrogen Regulatory Proteins
Multienzyme Complexes
Alcohol Dehydrogenase
Dietary thiamin level influences levels of its diphosphate form and thiamin-dependent enzymic activities of rat liver. (1/273)
This study was prompted by our incomplete understanding of the mechanism responsible for the clinical benefits of pharmacological doses of thiamin in some patients with maple syrup urine disease (MSUD) and the question of whether thiamin diphosphate (TDP), a potent inhibitor of the activity of the protein kinase that phosphorylates and inactivates the isolated branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex, affects the activity state of the complex. Rats were fed a chemically-defined diet containing graded levels of thiamin (0, 0.275, 0.55, 5.5, and 55 mg thiamin/kg diet). Maximal weight gain was attained over a 3-wk period only in rats fed diets with 5.5 and 55 mg thiamin/kg. Feeding rats the thiamin-free diet for just 2 d caused loss of nearly half of the TDP from liver mitochondria. Three more days caused over 70% loss, an additional 3 wk, over 90%. Starvation for 2 d had no effect, suggesting a mechanism for conservation of TDP in this nutritional state. Mitochondrial TDP was higher in rats fed pharmacological amounts of thiamin (55 mg thiamin/kg diet) than in rats fed adequate thiamin for maximal growth. Varying dietary thiamin had marked but opposite effects on the activities of alpha-ketoglutarate dehydrogenase (alpha-KGDH) and BCKDH. Thiamin deficiency decreased alpha-KGDH activity, increased BCKDH activity, and increased the proportion of BCKDH in the active, dephosphorylated, state. Excess dietary thiamin had the opposite effects. TDP appears to be more tightly associated with alpha-KGDH than BCKDH in thiamin-deficient rats, perhaps denoting retention of alpha-KGDH activity at the expense of BCKDH activity. Thus, thiamin deficiency and excess cause large changes in mitochondrial TDP levels that have a major influence on the activities of the keto acid dehydrogenase complexes. (+info)Declines in mitochondrial respiration during cardiac reperfusion: age-dependent inactivation of alpha-ketoglutarate dehydrogenase. (2/273)
We previously reported that cardiac reperfusion results in declines in mitochondrial NADH-linked respiration. The degree of inactivation increased with age and was paralleled by modification of protein by the lipid peroxidation product 4-hydroxy-2-nonenal. To gain insight into potential sites of oxidative damage, the present study was undertaken to identify specific mitochondrial protein(s) inactivated during ischemia and reperfusion and to determine which of these losses in activity are responsible for observed declines in mitochondrial respiration. Using a Langendorff rat heart perfusion protocol, we observed age-dependent inactivation of complex I during ischemia and complex IV and alpha-ketoglutarate dehydrogenase during reperfusion. Although losses in complex I and IV activities were found not to be of sufficient magnitude to cause declines in mitochondrial respiration, an age-related decrease in complex I activity during ischemia may predispose old animals to more severe oxidative damage during reperfusion. It was determined that inactivation of alpha-ketoglutarate dehydrogenase is responsible, in large part, for observed reperfusion-induced declines in NADH-linked respiration. alpha-Ketoglutarate dehydrogenase is highly susceptible to 4-hydroxy-2-nonenal inactivation in vitro. Thus, our results suggest a plausible mechanism for age-dependent, reperfusion-induced declines in mitochondrial function and identify alpha-ketoglutarate dehydrogenase as a likely site of free radical-mediated damage. (+info)Chemical modification of lysine and arginine residues of bovine heart 2-oxoglutarate dehydrogenase: effect on the enzyme activity and regulation. (3/273)
Chemical modification of arginine and lysine residues of bovine heart 2-oxoglutarate dehydrogenase with phenylglyoxal and pyridoxal 5'-phosphate inactivated the enzyme, indicating the importance of these residues for the catalysis. Inactivation caused by pyridoxal 5'-phosphate was prevented in the presence of thiamine pyrophosphate and Mg2+ allowing the assumption that lysine residues participate in binding of the cofactor. (+info)Plant mitochondrial 2-oxoglutarate dehydrogenase complex: purification and characterization in potato. (4/273)
The 2-oxoglutarate dehydrogenase complex (OGDC) in potato (Solanum tuberosum cv. Romano) tuber mitochondria is largely associated with the membrane fraction of osmotically ruptured organelles, whereas most of the other tricarboxylic acid cycle enzymes are found in the soluble matrix fraction. The purification of OGDC from either membrane or soluble matrix fractions resulted in the increasing dependence of its activity on the addition of dihydrolipoamide dehydrogenase (E3). A 30-fold purification of OGDC to apparent homogeneity and with a specific activity of 4.6 micromol/min per mg of protein in the presence of exogenously added E3 was obtained. SDS/PAGE revealed that the purified complex consisted of three major polypeptides with apparent molecular masses of 48, 50 and 105 kDa. Before the gel-filtration purification step, E3 polypeptides of 57 and 58 kDa were identified by immunoreaction as minor proteins associated with OGDC. The N-terminal sequence of the 57 kDa protein was identical with that previously purified as the E3 component of the pyruvate dehydrogenase complex from potato. The 105 kDa protein was identified as the 2-oxoglutarate dehydrogenase subunit of OGDC by N-terminal sequencing. The N-terminal sequences of the 50 and 48 kDa proteins shared 90-95% identity over 20 residues and were identified by sequence similarity as dihydrolipoamide succinyltransferases (OGDC-E2). The incubation of OGDC with [U-(14)C]2-oxoglutarate resulted in the reversible succinylation of both the 48 and the 50 kDa protein bands. Proteins previously reported as subunits of complex I of the respiratory chain from Vicia faba and Solanum tuberosum are proposed to be OGDC-E2 and the possible basis of this association is discussed. (+info)Neuronal pyruvate carboxylation supports formation of transmitter glutamate. (5/273)
Release of transmitter glutamate implies a drain of alpha-ketoglutarate from neurons, because glutamate, which is formed from alpha-ketoglutarate, is taken up by astrocytes. It is generally believed that this drain is compensated by uptake of glutamine from astrocytes, because neurons are considered incapable of de novo synthesis of tricarboxylic acid cycle intermediates, which requires pyruvate carboxylation. Here we show that cultured cerebellar granule neurons form releasable [(14)C]glutamate from H(14)CO(3)(-) and [1-(14)C]pyruvate via pyruvate carboxylation, probably mediated by malic enzyme. The activity of pyruvate carboxylation was calculated to be approximately one-third of the pyruvate dehydrogenase activity in neurons. Furthermore, intrastriatal injection of NaH(14)CO(3) or [1-(14)C]pyruvate labeled glutamate better than glutamine, showing that pyruvate carboxylation occurs in neurons in vivo. This means that neurons themselves to a large extent may support their release of glutamate, and thus entails a revision of the current view of glial-neuronal interactions and the importance of the glutamine cycle. (+info)Catabolism of alpha-ketoglutarate by a sucA mutant of Bradyrhizobium japonicum: evidence for an alternative tricarboxylic acid cycle. (6/273)
A complete tricarboxylic acid (TCA) cycle is generally considered necessary for energy production from the dicarboxylic acid substrates malate, succinate, and fumarate. However, a Bradyrhizobium japonicum sucA mutant that is missing alpha-ketoglutarate dehydrogenase is able to grow on malate as its sole source of carbon. This mutant also fixes nitrogen in symbiosis with soybean, where dicarboxylic acids are its principal carbon substrate. Using a flow chamber system to make direct measurements of oxygen consumption and ammonium excretion, we confirmed that bacteroids formed by the sucA mutant displayed wild-type rates of respiration and nitrogen fixation. Despite the absence of alpha-ketoglutarate dehydrogenase activity, whole cells of the mutant were able to decarboxylate alpha-[U-(14)C]ketoglutarate and [U-(14)C]glutamate at rates similar to those of wild-type B. japonicum, indicating that there was an alternative route for alpha-ketoglutarate catabolism. Because cell extracts from B. japonicum decarboxylated [U-(14)C]glutamate very slowly, the gamma-aminobutyrate shunt is unlikely to be the pathway responsible for alpha-ketoglutarate catabolism in the mutant. In contrast, cell extracts from both the wild type and mutant showed a coenzyme A (CoA)-independent alpha-ketoglutarate decarboxylation activity. This activity was independent of pyridine nucleotides and was stimulated by thiamine PP(i). Thin-layer chromatography showed that the product of alpha-ketoglutarate decarboxylation was succinic semialdehyde. The CoA-independent alpha-ketoglutarate decarboxylase, along with succinate semialdehyde dehydrogenase, may form an alternative pathway for alpha-ketoglutarate catabolism, and this pathway may enhance TCA cycle function during symbiotic nitrogen fixation. (+info)Zn2+ inhibits alpha-ketoglutarate-stimulated mitochondrial respiration and the isolated alpha-ketoglutarate dehydrogenase complex. (7/273)
Intracellular free Zn(2+) is elevated in a variety of pathological conditions, including ischemia-reperfusion injury and Alzheimer's disease. Impairment of mitochondrial respiration is also associated with these pathological conditions. To test whether elevated Zn(2+) and impaired respiration might be linked, respiration of isolated rat liver mitochondria was measured after addition of Zn(2+). Zn(2+) inhibition (K(i)(app) = approximately 1 micrometer) was observed for respiration stimulated by alpha-ketoglutarate at concentrations well within the range of intracellular Zn(2+) reported for cultured hepatocytes. The bc(1) complex is inhibited by Zn(2+) (Link, T. A., and von Jagow, G. (1995) J. Biol. Chem. 270, 25001-25006). However, respiration stimulated by succinate (K(i)(app) = approximately 6 micrometer) was less sensitive to Zn(2+), indicating the existence of a mitochondrial target for Zn(2+) upstream from bc(1) complex. Purified pig heart alpha-ketoglutarate dehydrogenase complex was strongly inhibited by Zn(2+) (K(i)(app) = 0.37 +/- 0.05 micrometer). Glutamate dehydrogenase was more resistant (K(i)(app) = 6 micrometer), malate dehydrogenase was unaffected, and succinate dehydrogenase was stimulated by Zn(2+). Zn(2+) inhibition of alpha-ketoglutarate dehydrogenase complex required enzyme cycling and was reversed by EDTA. Reversibility was inversely related to the duration of exposure and the concentration of Zn(2+). Physiological free Zn(2+) may modulate hepatic mitochondrial respiration by reversible inhibition of the alpha-ketoglutarate dehydrogenase complex. In contrast, extreme or chronic elevation of intracellular Zn(2+) could contribute to persistent reductions in mitochondrial respiration that have been observed in Zn(2+)-rich diseased tissues. (+info)Cloning, overexpression and mutagenesis of cDNA encoding dihydrolipoamide succinyltransferase component of the porcine 2-oxoglutarate dehydrogenase complex. (8/273)
Dihydrolipoamide succinyltransferase (E2o) is the structural and catalytic core of the 2-oxoglutarate dehydrogenase (OGDH) complex. The cDNA encoding porcine E2o (PE2o) has been cloned. The PE2o cDNA spans 2547 bases encoding a presequence (68 amino-acid residues) and a mature protein (387 residues, Mr = 41 534). Recombinant porcine E2o (rPE2o) (residues 1-387), C- and N-terminal truncated PE2os, and site-directed mutant PE2os were overexpressed in Escherichia coli via the expression vector pET-11d and purified. The succinyltransferase activity of the rPE2o was about 2.2-fold higher than that of the native PE2o. Electron micrographs of the rPE2o negatively stained showed a cube-like structure very similar to that of the native PE2o. Deletion of five amino-acid residues from the C-terminus resulted in a complete loss of both enzymatic activity and formation of the cube-like structure, but the deletion of only the last two residues had no effect on either function, suggesting the important roles of the C-terminal leucine triplet (Leu383-384-385). Substitution of Ser306 with Ala, and Asp362 with Asn, Glu or Ala in the putative active site, and Leu383-384-385 with Ala or Asp abolished both functions. Substitution of His358 with Cys resulted in an 8.5-fold reduction in kcat, with little change in Km values for dihydrolipoamide and succinyl-CoA. However, self-assembly was not affected. These data indicate that Ser306, Asp362 and the Leu383-384-385 triplet are important residues in both the self-assembly and catalytic mechanism of PE2o. (+info)The Ketoglutarate Dehydrogenase Complex (KGDC or α-KGDH) is a multi-enzyme complex that plays a crucial role in the Krebs cycle, also known as the citric acid cycle. It is located within the mitochondrial matrix of eukaryotic cells and functions to catalyze the oxidative decarboxylation of α-ketoglutarate into succinyl-CoA, thereby connecting the Krebs cycle to the electron transport chain for energy production.
The KGDC is composed of three distinct enzymes:
1. α-Ketoglutarate dehydrogenase (E1): This enzyme catalyzes the decarboxylation and oxidation of α-ketoglutarate to form a thioester intermediate with lipoamide, which is bound to the E2 component.
2. Dihydrolipoyl succinyltransferase (E2): This enzyme facilitates the transfer of the acetyl group from the lipoamide cofactor to CoA, forming succinyl-CoA and regenerating oxidized lipoamide.
3. Dihydrolipoyl dehydrogenase (E3): The final enzyme in the complex catalyzes the reoxidation of reduced lipoamide back to its disulfide form, using FAD as a cofactor and transferring electrons to NAD+, forming NADH.
The KGDC is subject to regulation by several mechanisms, including phosphorylation-dephosphorylation reactions that can inhibit or activate the complex, respectively. Dysfunction of this enzyme complex has been implicated in various diseases, such as neurodegenerative disorders and cancer.
The Pyruvate Dehydrogenase Complex (PDC) is a multi-enzyme complex that plays a crucial role in cellular energy metabolism. It is located in the mitochondrial matrix and catalyzes the oxidative decarboxylation of pyruvate, the end product of glycolysis, into acetyl-CoA. This reaction links the carbohydrate metabolism (glycolysis) to the citric acid cycle (Krebs cycle), enabling the continuation of energy production in the form of ATP through oxidative phosphorylation.
The Pyruvate Dehydrogenase Complex consists of three main enzymes: pyruvate dehydrogenase (E1), dihydrolipoyl transacetylase (E2), and dihydrolipoyl dehydrogenase (E3). Additionally, two regulatory enzymes are associated with the complex: pyruvate dehydrogenase kinase (PDK) and pyruvate dehydrogenase phosphatase (PDP). These regulatory enzymes control the activity of the PDC through reversible phosphorylation and dephosphorylation, allowing the cell to adapt to varying energy demands and substrate availability.
Deficiencies or dysfunctions in the Pyruvate Dehydrogenase Complex can lead to various metabolic disorders, such as pyruvate dehydrogenase deficiency, which may result in neurological impairments and lactic acidosis due to disrupted energy metabolism.
Alpha-ketoglutaric acid, also known as 2-oxoglutarate, is not an acid in the traditional sense but is instead a key molecule in the Krebs cycle (citric acid cycle), which is a central metabolic pathway involved in cellular respiration. Alpha-ketoglutaric acid is a crucial intermediate in the process of converting carbohydrates, fats, and proteins into energy through oxidation. It plays a vital role in amino acid synthesis and the breakdown of certain amino acids. Additionally, it serves as an essential cofactor for various enzymes involved in numerous biochemical reactions within the body. Any medical conditions or disorders related to alpha-ketoglutaric acid would typically be linked to metabolic dysfunctions or genetic defects affecting the Krebs cycle.
Ketone oxidoreductases are a group of enzymes that catalyze the conversion of ketones to corresponding alcohols or vice versa, through the process of reduction or oxidation. These enzymes play an essential role in various metabolic pathways and biochemical reactions within living organisms.
In the context of medical research and diagnostics, ketone oxidoreductases have gained attention for their potential applications in the development of biosensors to detect and monitor blood ketone levels, particularly in patients with diabetes. Elevated levels of ketones in the blood (known as ketonemia) can indicate a serious complication called diabetic ketoacidosis, which requires prompt medical attention.
One example of a ketone oxidoreductase is the enzyme known as d-beta-hydroxybutyrate dehydrogenase (d-BDH), which catalyzes the conversion of d-beta-hydroxybutyrate to acetoacetate. This reaction is part of the metabolic pathway that breaks down fatty acids for energy production, and it becomes particularly important during periods of low carbohydrate availability or insulin deficiency, as seen in diabetes.
Understanding the function and regulation of ketone oxidoreductases can provide valuable insights into the pathophysiology of metabolic disorders like diabetes and contribute to the development of novel therapeutic strategies for their management.
Dihydrolipoamide dehydrogenase (DHLD) is an enzyme that plays a crucial role in several important metabolic pathways in the human body, including the citric acid cycle and the catabolism of certain amino acids. DHLD is a component of multi-enzyme complexes, such as the pyruvate dehydrogenase complex (PDC) and the alpha-ketoglutarate dehydrogenase complex (KGDC).
The primary function of DHLD is to catalyze the oxidation of dihydrolipoamide, a reduced form of lipoamide, back to its oxidized state (lipoamide) while simultaneously reducing NAD+ to NADH. This reaction is essential for the continued functioning of the PDC and KGDC, as dihydrolipoamide is a cofactor for these enzyme complexes.
Deficiencies in DHLD can lead to serious metabolic disorders, such as maple syrup urine disease (MSUD) and riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (RR-MADD). These conditions can result in neurological symptoms, developmental delays, and metabolic acidosis, among other complications. Treatment typically involves dietary modifications, supplementation with specific nutrients, and, in some cases, enzyme replacement therapy.
Dihydrolipoyllysine-residue acetyltransferase is a type of enzyme that plays a crucial role in the cellular process of energy production, specifically in the citric acid cycle (also known as the Krebs cycle or tricarboxylic acid cycle). This enzyme is responsible for transferring an acetyl group from acetyl-CoA to a specific residue on another protein called dihydrolipoyl dehydrogenase.
The reaction catalyzed by this enzyme can be summarized as follows:
Acetyl-CoA + dihydrolipoyl dehydrogenase (E3-DHLA) -> CoA + acetylated-dihydrolipoyl dehydrogenase (E3-DHLAA)
The acetylation of the dihydrolipoyl dehydrogenase protein is a necessary step in the citric acid cycle, which helps generate energy in the form of ATP through a series of oxidation-reduction reactions. Defects or mutations in this enzyme can lead to various metabolic disorders and diseases.
Keto acids, also known as ketone bodies, are not exactly the same as "keto acids" in the context of amino acid metabolism.
In the context of metabolic processes, ketone bodies are molecules that are produced as byproducts when the body breaks down fat for energy instead of carbohydrates. When carbohydrate intake is low, the liver converts fatty acids into ketone bodies, which can be used as a source of energy by the brain and other organs. The three main types of ketone bodies are acetoacetate, beta-hydroxybutyrate, and acetone.
However, in the context of amino acid metabolism, "keto acids" refer to the carbon skeletons of certain amino acids that remain after their nitrogen-containing groups have been removed during the process of deamination. These keto acids can then be converted into glucose or used in other metabolic pathways. For example, the keto acid produced from the amino acid leucine is called beta-ketoisocaproate.
Therefore, it's important to clarify the context when discussing "keto acids" as they can refer to different things depending on the context.
Pyruvate Dehydrogenase Complex (PDH) Deficiency is a genetic disorder that affects the body's ability to convert certain food molecules into energy. The pyruvate dehydrogenase complex is a group of enzymes that converts pyruvate, a byproduct of glucose metabolism in the cell's cytoplasm, into acetyl-CoA, which then enters the citric acid cycle (also known as the Krebs cycle) in the mitochondria to produce energy in the form of ATP.
PDH deficiency results from mutations in one or more genes encoding the subunits of the PDH complex or its activators, leading to reduced enzymatic activity. This impairs the conversion of pyruvate to acetyl-CoA and causes an accumulation of pyruvate in body tissues and fluids, particularly during periods of metabolic stress such as illness, infection, or fasting.
The severity of PDH deficiency can vary widely, from mild to severe forms, depending on the extent of enzyme dysfunction. Symptoms may include developmental delay, hypotonia (low muscle tone), seizures, poor feeding, and metabolic acidosis. In severe cases, it can lead to neurological damage, lactic acidosis, and early death if not diagnosed and treated promptly.
PDH deficiency is typically diagnosed through biochemical tests that measure the activity of the PDH complex in cultured skin fibroblasts or muscle tissue. Genetic testing may also be used to identify specific gene mutations causing the disorder. Treatment usually involves a low-carbohydrate, high-fat diet and supplementation with thiamine (vitamin B1), which is an essential cofactor for PDH complex activity. In some cases, dialysis or other supportive measures may be necessary to manage metabolic acidosis and other complications.
UDP-glucose-hexose-1-phosphate uridylyltransferase is an enzyme that plays a role in the metabolism of carbohydrates. The systematic name for this enzyme is UDP-glucose:alpha-D-hexose-1-phosphate uridylyltransferase.
This enzyme catalyzes the following reaction:
UDP-glucose + alpha-D-hexose 1-phosphate glucose 1-phosphate + UDP-alpha-D-hexose
In simpler terms, this enzyme helps to transfer a uridylyl group (UDP) from UDP-glucose to another hexose sugar that is attached to a phosphate group. This reaction allows for the interconversion of different sugars in the cell and plays a role in various metabolic pathways, including the synthesis of glycogen and other complex carbohydrates.
Deficiencies or mutations in this enzyme can lead to various genetic disorders, such as congenital disorder of glycosylation type IIb (CDGIIb) and polycystic kidney disease.
Transaminases, also known as aminotransferases, are a group of enzymes found in various tissues of the body, particularly in the liver, heart, muscle, and kidneys. They play a crucial role in the metabolism of amino acids, the building blocks of proteins.
There are two major types of transaminases: aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Both enzymes are normally present in low concentrations in the bloodstream. However, when tissues that contain these enzymes are damaged or injured, such as during liver disease or muscle damage, the levels of AST and ALT in the blood may significantly increase.
Measurement of serum transaminase levels is a common laboratory test used to assess liver function and detect liver injury or damage. Increased levels of these enzymes in the blood can indicate conditions such as hepatitis, liver cirrhosis, drug-induced liver injury, heart attack, and muscle disorders. It's important to note that while elevated transaminase levels may suggest liver disease, they do not specify the type or cause of the condition, and further diagnostic tests are often required for accurate diagnosis and treatment.
Saccharopine dehydrogenases are enzymes involved in the metabolism of the amino acid lysine. These enzymes catalyze the conversion of saccharopine, an intermediate compound in the lysine degradation pathway, into α-aminoadipic semialdehyde and glutamate. Saccharopine dehydrogenases play a crucial role in maintaining the balance of amino acids in the body and are found in various organisms, including bacteria, plants, and animals. In humans, mutations in the gene encoding one form of saccharopine dehydrogenase (Lysine Ketoglutarate Reductase/Saccharopine Dehydrogenase) have been associated with a rare genetic disorder called saccharopinuria, which is characterized by elevated levels of saccharopine in the urine and neurological symptoms.
Oxaloacetates are organic compounds that are integral to the Krebs cycle, also known as the citric acid cycle, in biological energy production. Specifically, oxaloacetate is an important intermediate compound within this metabolic pathway, found in the mitochondria of cells.
In the context of a medical definition, oxaloacetates are not typically referred to directly. Instead, the term "oxaloacetic acid" might be used, which is the conjugate acid of the oxaloacetate ion. Oxaloacetic acid has the chemical formula C4H4O5 and appears in various biochemical reactions as a crucial component of cellular respiration.
The Krebs cycle involves several stages where oxaloacetic acid plays a significant role:
1. In the first step, oxaloacetic acid combines with an acetyl group (derived from acetyl-CoA) to form citric acid, releasing coenzyme A in the process. This reaction is catalyzed by citrate synthase.
2. Throughout subsequent steps of the cycle, citric acid undergoes a series of reactions that generate energy in the form of NADH and FADH2 (reduced forms of nicotinamide adenine dinucleotide and flavin adenine dinucleotide, respectively), as well as GTP (guanosine triphosphate).
3. At the end of the cycle, oxaloacetic acid is regenerated to continue the process anew. This allows for continuous energy production within cells.
In summary, while "oxaloacetates" isn't a standard term in medical definitions, it does refer to an essential component (oxaloacetic acid) of the Krebs cycle that plays a critical role in cellular respiration and energy production.
Coenzyme A, often abbreviated as CoA or sometimes holo-CoA, is a coenzyme that plays a crucial role in several important chemical reactions in the body, particularly in the metabolism of carbohydrates, fatty acids, and amino acids. It is composed of a pantothenic acid (vitamin B5) derivative called pantothenate, an adenosine diphosphate (ADP) molecule, and a terminal phosphate group.
Coenzyme A functions as a carrier molecule for acetyl groups, which are formed during the breakdown of carbohydrates, fatty acids, and some amino acids. The acetyl group is attached to the sulfur atom in CoA, forming acetyl-CoA, which can then be used as a building block for various biochemical pathways, such as the citric acid cycle (Krebs cycle) and fatty acid synthesis.
In summary, Coenzyme A is a vital coenzyme that helps facilitate essential metabolic processes by carrying and transferring acetyl groups in the body.
Thioctic acid is also known as alpha-lipoic acid. It is a vitamin-like chemical compound that is made naturally in the body and is found in small amounts in some foods like spinach, broccoli, and potatoes. Thioctic acid is an antioxidant that helps to protect cells from damage caused by free radicals. It also plays a role in energy production in the cells and has been studied for its potential benefits in the treatment of diabetes and nerve-related symptoms of diabetes such as pain, burning, itching, and numbness. Thioctic acid is available as a dietary supplement.
Medical Definition: Thioctic acid (also known as alpha-lipoic acid) is a vitamin-like antioxidant that is made naturally in the body and is found in small amounts in some foods. It plays a role in energy production in the cells, and has been studied for its potential benefits in the treatment of diabetes and nerve-related symptoms of diabetes such as pain, burning, itching, and numbness. Thioctic acid is also available as a dietary supplement.
Ornithine is not a medical condition but a naturally occurring alpha-amino acid, which is involved in the urea cycle, a process that eliminates ammonia from the body. Here's a brief medical/biochemical definition of Ornithine:
Ornithine (NH₂-CH₂-CH₂-CH(NH₃)-COOH) is an α-amino acid without a carbon atom attached to the amino group, classified as a non-proteinogenic amino acid because it is not encoded by the standard genetic code and not commonly found in proteins. It plays a crucial role in the urea cycle, where it helps convert harmful ammonia into urea, which can then be excreted by the body through urine. Ornithine is produced from the breakdown of arginine, another amino acid, via the enzyme arginase. In some medical and nutritional contexts, ornithine supplementation may be recommended to support liver function, wound healing, or muscle growth, but its effectiveness for these uses remains a subject of ongoing research and debate.
Glutarates are compounds that contain a glutaric acid group. Glutaric acid is a carboxylic acid with a five-carbon chain and two carboxyl groups at the 1st and 5th carbon positions. Glutarates can be found in various substances, including certain foods and medications.
In a medical context, glutarates are sometimes used as ingredients in pharmaceutical products. For example, sodium phenylbutyrate, which is a salt of phenylbutyric acid and butyric acid, contains a glutaric acid group and is used as a medication to treat urea cycle disorders.
Glutarates can also be found in some metabolic pathways in the body, where they play a role in energy production and other biochemical processes. However, abnormal accumulation of glutaric acid or its derivatives can lead to certain medical conditions, such as glutaric acidemia type I, which is an inherited disorder of metabolism that can cause neurological symptoms and other health problems.
Thiamine pyrophosphate (TPP) is the active form of thiamine (vitamin B1) that plays a crucial role as a cofactor in various enzymatic reactions, particularly in carbohydrate metabolism. TPP is essential for the functioning of three key enzymes: pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and transketolase. These enzymes are involved in critical processes such as the conversion of pyruvate to acetyl-CoA, the oxidative decarboxylation of alpha-ketoglutarate in the Krebs cycle, and the pentose phosphate pathway, which is important for generating reducing equivalents (NADPH) and ribose sugars for nucleotide synthesis. A deficiency in thiamine or TPP can lead to severe neurological disorders, including beriberi and Wernicke-Korsakoff syndrome, which are often observed in alcoholics due to poor nutrition and impaired thiamine absorption.
L-Lactate Dehydrogenase (LDH) is an enzyme found in various tissues within the body, including the heart, liver, kidneys, muscles, and brain. It plays a crucial role in the process of energy production, particularly during anaerobic conditions when oxygen levels are low.
In the presence of the coenzyme NADH, LDH catalyzes the conversion of pyruvate to lactate, generating NAD+ as a byproduct. Conversely, in the presence of NAD+, LDH can convert lactate back to pyruvate using NADH. This reversible reaction is essential for maintaining the balance between lactate and pyruvate levels within cells.
Elevated blood levels of LDH may indicate tissue damage or injury, as this enzyme can be released into the circulation following cellular breakdown. As a result, LDH is often used as a nonspecific biomarker for various medical conditions, such as myocardial infarction (heart attack), liver disease, muscle damage, and certain types of cancer. However, it's important to note that an isolated increase in LDH does not necessarily pinpoint the exact location or cause of tissue damage, and further diagnostic tests are usually required for confirmation.
PII nitrogen regulatory proteins are a type of signal transduction protein involved in the regulation of nitrogen metabolism in bacteria and archaea. They are named "PII" because they contain two identical subunits, each with a molecular weight of approximately 12 kilodaltons. These proteins play a crucial role in sensing and responding to changes in the energy status and nitrogen availability within the cell.
The PII protein is composed of three domains: the T-domain, which binds ATP and ADP; the N-domain, which binds 2-oxoglutarate (an indicator of carbon and nitrogen status); and the B-domain, which is involved in signal transduction. The PII protein can exist in different conformational states depending on whether it is bound to ATP or ADP, and this affects its ability to interact with downstream effectors.
One of the primary functions of PII proteins is to regulate the activity of glutamine synthetase (GS), an enzyme that catalyzes the conversion of glutamate to glutamine. When nitrogen is abundant, PII proteins bind to GS and stimulate its activity, promoting the assimilation of ammonia into organic compounds. Conversely, when nitrogen is scarce, PII proteins dissociate from GS, allowing it to be inhibited by other regulatory proteins.
PII proteins can also interact with other enzymes and regulators involved in nitrogen metabolism, such as nitrogenase, uridylyltransferase/uridylyl-removing enzyme (UT/UR), and transcriptional regulators. Through these interactions, PII proteins help to coordinate the cell's response to changes in nitrogen availability and energy status, ensuring that resources are allocated efficiently and effectively.
Multienzyme complexes are specialized protein structures that consist of multiple enzymes closely associated or bound together, often with other cofactors and regulatory subunits. These complexes facilitate the sequential transfer of substrates along a series of enzymatic reactions, also known as a metabolic pathway. By keeping the enzymes in close proximity, multienzyme complexes enhance reaction efficiency, improve substrate specificity, and maintain proper stoichiometry between different enzymes involved in the pathway. Examples of multienzyme complexes include the pyruvate dehydrogenase complex, the citrate synthase complex, and the fatty acid synthetase complex.
Alcohol dehydrogenase (ADH) is a group of enzymes responsible for catalyzing the oxidation of alcohols to aldehydes or ketones, and reducing equivalents such as NAD+ to NADH. In humans, ADH plays a crucial role in the metabolism of ethanol, converting it into acetaldehyde, which is then further metabolized by aldehyde dehydrogenase (ALDH) into acetate. This process helps to detoxify and eliminate ethanol from the body. Additionally, ADH enzymes are also involved in the metabolism of other alcohols, such as methanol and ethylene glycol, which can be toxic if allowed to accumulate in the body.
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.