PDK4
Pyruvate dehydrogenase lipoamide kinase isozyme 4, mitochondrial (PDK4) is an enzyme that in humans is encoded by the ''PDK4'' gene. It codes for an isozyme of pyruvate dehydrogenase kinase. This gene is a member of the PDK/BCKDK protein kinase family and encodes a mitochondrial protein with a histidine kinase domain. This protein is located in the matrix of the mitochondria and inhibits the pyruvate dehydrogenase complex by phosphorylating one of its subunits, reducing the conversion of pyruvate, which is produced from the oxidation of glucose and amino acids, to acetyl-CoA and contributing to the regulation of glucose metabolism. Expression of this gene is regulated by glucocorticoids, retinoic acid and insulin. PDK4 is increased in hibernation and helps to decrease metabolism and conserve glucose by decreasing its conversion to acetyl-CoA, which enters the citric acid cycle and is converted to ATP. Structure The mature protein encoded by the ''PDK4'' gene contains 294 ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Pyruvate Dehydrogenase Kinase
Pyruvate dehydrogenase kinase (also pyruvate dehydrogenase complex kinase, PDC kinase, or PDK; ) is a kinase enzyme which acts to inactivate the enzyme pyruvate dehydrogenase by phosphorylating it using ATP. PDK thus participates in the regulation of the pyruvate dehydrogenase complex of which pyruvate dehydrogenase is the first component. Both PDK and the pyruvate dehydrogenase complex are located in the mitochondrial matrix of eukaryotes. The complex acts to convert pyruvate (a product of glycolysis in the cytosol) to acetyl-coA, which is then oxidized in the mitochondria to produce energy, in the citric acid cycle. By downregulating the activity of this complex, PDK will decrease the oxidation of pyruvate in mitochondria and increase the conversion of pyruvate to lactate in the cytosol. The opposite action of PDK, namely the dephosphorylation and activation of pyruvate dehydrogenase, is catalyzed by a phosphoprotein phosphatase called pyruvate dehydrogenase phosphatase. ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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PDK2
Pyruvate dehydrogenase kinase isoform 2 (PDK2) also known as pyruvate dehydrogenase lipoamide kinase isozyme 2, mitochondrial is an enzyme that in humans is encoded by the ''PDK2'' gene. PDK2 is an isozyme of pyruvate dehydrogenase kinase. Structure The protein encoded by the PDK2 gene has two sites, an active site and an allosteric site that allow for the activity and regulation of this enzyme. There are many structural motifs that are important to the regulation of this enzyme. Nov3r and AZ12 inhibitors bind at the lipoamide binding site that is located at one end of the R domain. Pfz3 binds in an extended site at the other end of the R domain. One inhibitor, dicholoroacetate (DCA), binds at the center of the R domain. Within the active site, there are three amino acid residues, R250, T302, and Y320, that make the kinase resistant to the inhibitor dichloroacetate, which uncouples the active site from the allosteric site. This supports the theory that R250, T302, and Y320 stabi ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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PDK3
Pyruvate dehydrogenase lipoamide kinase isozyme 3, mitochondrial is an enzyme that in humans is encoded by the ''PDK3'' gene. It codes for an isozyme of pyruvate dehydrogenase kinase.The pyruvate dehydrogenase (PDH) complex is a nuclear-encoded mitochondrial multienzyme complex that catalyzes the overall conversion of pyruvate to acetyl-CoA and CO2. It provides the primary link between glycolysis and the tricarboxylic acid (TCA) cycle, and thus is one of the major enzymes responsible for the regulation of glucose metabolism. The enzymatic activity of PDH is regulated by a phosphorylation/dephosphorylation cycle, and phosphorylation results in inactivation of PDH. The protein encoded by this gene is one of the four pyruvate dehydrogenase kinases that inhibits the PDH complex by phosphorylation of the E1 alpha subunit. This gene is predominantly expressed in the heart and skeletal muscles. Alternatively spliced transcript variants encoding different isoforms have been found for thi ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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PDK1
Pyruvate dehydrogenase lipoamide kinase isozyme 1, mitochondrial is an enzyme that in humans is encoded by the ''PDK1'' gene. It codes for an isozyme of pyruvate dehydrogenase kinase (PDK). Pyruvate dehydrogenase (PDH) is a part of a mitochondrial multienzyme complex that catalyzes the oxidative decarboxylation of pyruvate and is one of the major enzymes responsible for the regulation of homeostasis of carbohydrate fuels in mammals. The enzymatic activity is regulated by a phosphorylation/dephosphorylation cycle. Phosphorylation of PDH by a specific pyruvate dehydrogenase kinase (PDK) results in inactivation. Structure The mature protein encoded by the PDK4 gene contains 407 amino acids in its sequence. To form the active protein, two of the polypeptide chains come together to form an open conformation. The catalytic domain of PDK1 might exist separately in cells and important for the regulation of the PDK1 substrate. The crystal structural studies suggest that the PIF-pocket is ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecules known as product (chemistry), products. Almost all metabolism, metabolic processes in the cell (biology), cell need enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic pathways depend upon enzymes to catalyze individual steps. The study of enzymes is called ''enzymology'' and the field of pseudoenzyme, pseudoenzyme analysis recognizes that during evolution, some enzymes have lost the ability to carry out biological catalysis, which is often reflected in their amino acid sequences and unusual 'pseudocatalytic' properties. Enzymes are known to catalyze more than 5,000 biochemical reaction types. Other biocatalysts include Ribozyme, catalytic RNA molecules, also called ribozymes. They are sometimes descr ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabolism of carbohydrates, fats, and protein by promoting the absorption of glucose from the blood into cells of the liver, fat cell, fat, and skeletal muscles. In these tissues the absorbed glucose is converted into either glycogen, via glycogenesis, or Fatty acid metabolism#Glycolytic end products are used in the conversion of carbohydrates into fatty acids, fats (triglycerides), via lipogenesis; in the liver, glucose is converted into both. Glucose production and secretion by the liver are strongly inhibited by high concentrations of insulin in the blood. Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is thus an anabolic hormone, promoting the conversion of small molecules in the blood into large ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Retinoic Acid
Retinoic acid (simplified nomenclature for all-''trans''-retinoic acid) is a metabolite of vitamin A1 (all-''trans''-retinol) that is required for embryonic development, male fertility, regulation of bone growth and immune function. All-''trans''-retinoic acid is required for chordate animal development, which includes all higher animals from fish to humans. During early embryonic development, all-''trans''-retinoic acid generated in a specific region of the embryo helps determine position along the embryonic anterior/posterior axis by serving as an intercellular signaling molecule that guides development of the posterior portion of the embryo. It acts through Hox genes, which ultimately control anterior/posterior patterning in early developmental stages. In adult tissues, the activity of endogenous retinoic acid appears limited to immune function and male fertility. All-''trans''-retinoic acid is the major occurring retinoic acid, while isomers like 13-''cis''- and 9-''cis''-r ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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CCAAT Box
In molecular biology, a CCAAT box (also sometimes abbreviated a CAAT box or CAT box) is a distinct pattern of nucleotides with GGCCAATCT consensus sequence that occur upstream by 60–100 bases to the initial transcription site. The CAAT box signals the binding site for the RNA transcription factor, and is typically accompanied by a conserved consensus sequence. It is an invariant DNA sequence at about minus 70 base pairs from the origin of transcription in many eukaryotic promoters. Genes that have this element seem to require it for the gene to be transcribed in sufficient quantities. It is frequently absent from genes that encode proteins used in virtually all cells. This box along with the GC box is known for binding general transcription factors. Both of these consensus sequences belong to the regulatory promoter. Full gene expression occurs when transcription activator proteins bind to each module within the regulatory promoter. Protein specific binding is required for th ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Sp1 Transcription Factor
Transcription factor Sp1, also known as specificity protein 1* is a protein that in humans is encoded by the ''SP1'' gene. Function The protein encoded by this gene is a zinc finger transcription factor that binds to GC-rich motifs of many promoters. The encoded protein is involved in many cellular processes, including cell differentiation, cell growth, apoptosis, immune responses, response to DNA damage, and chromatin remodeling. post-translational modifications such as phosphorylation, acetylation, ''O''-GlcNAcylation, and proteolytic processing significantly affect the activity of this protein, which can be an activator or a repressor. In the SV40 virus, Sp1 binds to the GC boxes in the regulatory sequence of the genome. Structure SP1 belongs to the Sp/KLF family of transcription factors. The protein is 785 amino acids long, with a molecular weight of 81 kDa. The SP1 transcription factor contains two glutamine-rich activation domains at its N-terminus that ar ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Coenzyme
A cofactor is a non-protein chemical compound or Metal ions in aqueous solution, metallic ion that is required for an enzyme's role as a catalysis, catalyst (a catalyst is a substance that increases the rate of a chemical reaction). Cofactors can be considered "helper molecules" that assist in Biochemistry, biochemical transformations. The rates at which these happen are characterized in an area of study called enzyme kinetics. Cofactors typically differ from Ligand (biochemistry), ligands in that they often derive their function by remaining bound. Cofactors can be classified into two types: inorganic ions and complex organic molecules called Enzyme#Coenzymes, coenzymes. Coenzymes are mostly derived from vitamins and other organic essential nutrients in small amounts. (Some scientists limit the use of the term "cofactor" for inorganic substances; both types are included here.) Coenzymes are further divided into two types. The first is called a "prosthetic group", which consists ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Thiamine Pyrophosphate
Thiamine pyrophosphate (TPP or ThPP), or thiamine diphosphate (ThDP), or cocarboxylase is a thiamine (vitamin B1) derivative which is produced by the enzyme thiamine diphosphokinase. Thiamine pyrophosphate is a cofactor that is present in all living systems, in which it catalyzes several biochemical reactions. Thiamine pyrophosphate is synthesized in the cytosol and is required in the cytosol for the activity of transketolase and in the mitochondria for the activity of pyruvate-, oxoglutarate- and branched chain keto acid dehydrogenases. To date, the yeast ThPP carrier (Tpc1p) the human Tpc and the ''Drosophila melanogaster'' have been identified as being responsible for the mitochondrial transport of ThPP and ThMP. It was first discovered as an essential nutrient (vitamin) in humans through its link with the peripheral nervous system disease beriberi, which results from a deficiency of thiamine in the diet. TPP works as a coenzyme in many enzymatic reactions, such as: * Pyru ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Isozymes
In biochemistry, isozymes (also known as isoenzymes or more generally as multiple forms of enzymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. Isozymes usually have different kinetic parameters (e.g. different ''K''M values), or are regulated differently. They permit the fine-tuning of metabolism to meet the particular needs of a given tissue or developmental stage. In many cases, isozymes are encoded by homologous genes that have diverged over time. Strictly speaking, enzymes with different amino acid sequences that catalyse the same reaction are isozymes if encoded by different genes, or allozymes if encoded by different alleles of the same gene; the two terms are often used interchangeably. Introduction Isozymes were first described by R. L. Hunter and Clement Markert (1957) who defined them as ''different variants of the same enzyme having identical functions and present in the same individual''. This definition encompasses ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |