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20-September-2008 09:55:58 - carboxylase Acetyl-Coenzyme A carboxylase alpha Identifiers Symbol ACACA Alt. Symbols ACAC, ACC1, ACCA Entrez 31 HUGO 84 OMIM 601557 RefSeq NM_198839 UniProt Q13085 Other data EC number 6.4.1.2 Locus Chr. 17 q21 Acetyl-Coenzyme A carboxylase beta Identifiers Symbol ACACB Alt. Symbols ACC2, ACCB Entrez 32 HUGO 85 OMIM 200350 RefSeq NM_001093 UniProt O00763 Other data EC number 6.4.1.2 Locus Chr. 12 q24.1 Acetyl-CoA carboxylase ACC is a biotin-dependent enzyme that catalyses the irreversible carboxylation of acetyl-CoA to produce malonyl-CoA through its two catalytic activities, biotin carboxylase BC and carboxyltransferase CT. In muscle cells, this inhibits beta-oxidation. ACC is a multi-subunit enzyme in most prokaryotes, whereas it is a large, multi-domain enzyme in most eukaryotes. The activity of ACC can be controlled at the transcriptional level as well as by small molecule modulators and covalent modification. Human genome contains the genes for two different ACCs - ACACA and ACACB. Contents 1 Structure 2 Mechanism 3 Function 4 Regulation 5 Clinical implications 6 See also 7 References Structure ACACA 2346 aa and ACACB 2483 aa have four functional regions each, starting from NH2- to COOH-terminal: biotin carboxylating BC, biotin binding BB, carboxyltransferase CT, and ATP-binding AB. AT lies within BC. Biotin is covalently attached through an amide bond to the long side chain of a lysine reside in BB. As BB is between BC and CT regions, biotin can be easily delivered to their active sites. Mechanism The overall reaction of ACACA,B proceeds by a two-step mechanism. The first half-reaction is carried out by BC and involves the ATP-dependent carboxylation of biotin with bicarbonate serving as the source of CO2. The carboxyl group is transferred from biotin to acetyl CoA to form malonyl CoA in the second half-reaction, which is catalyzed by CT. The reaction mechanism of ACACA,B.The color scheme is as follows: enzyme, coenzymes, substrate names, metal ions, phosphate, and carbonate The reaction mechanism of ACACA,B. The color scheme is as follows: enzyme, coenzymes, substrate names, metal ions, phosphate, and carbonate Function In muscle cells, the function of ACAC is to regulate the fatty mechanism. When the enzyme is active, the product, malonyl-CoA is produced and inhibit the transfer of the fatty acyl group from acyl CoA to carnitine with carnitine acyltransferase, which inhibits the beta-oxidation of the fatty acid in mitochondria. Regulation The inactive dimer form of this enzyme is induced to polymerize by citrate, resulting in the active polymer form. The activity of the enzyme is controlled by the reversible phosphorylation. The activities of the enzyme is inhibited if phosphorylated; the phosphorylation takes place when the hormones, glucagon or epinephrine bind to the receptors or the energy status of the cell is low, leading to the activation of the AMP-activated protein kinase. The presence of fatty acid inhibits the activities of the enzyme. When insulin binds to its receptors of the cell, it activates a phosphatase to dephosphorylate the enzyme; the activities of the acetyl-CoA carboxylase is thus enhanced. Clinical implications Bacterial Acetyl-CoA carboxylase has recently become a target in the design of new anti-obesity and antibiotic drugs. See also Malonyl-CoA decarboxylase References Levert K, Waldrop G, Stephens J 2002. A biotin analog inhibits acetyl-CoA carboxylase activity and adipogenesis. J. Biol. Chem. 277 19: 16347-50. doi:10.1074/jbc.C200113200. PMID 11907024. v d e Ligases: carbon-carbon ligases EC 6.4 Pyruvate carboxylase - Acetyl-CoA carboxylase - Propionyl-CoA carboxylase - Methylcrotonyl-CoA carboxylase - Polyketide synthase v d e Metabolism: lipid metabolism - triglyceride and fatty acid enzymes Lipid production ATP citrate lyase - Acetyl-CoA carboxylase Fatty acid synthesis/Fatty acid synthase: Beta-ketoacyl-ACP synthase - Β-Ketoacyl ACP reductase - 3-Hydroxyacyl ACP dehydrase - Enoyl ACP reductase triacyl glycerol: Glycerol-3-phosphate dehydrogenase - Thiokinase Lipid degradation Acyl transport: Carnitine palmitoyltransferase I - Carnitine-acylcarnitine translocase - Carnitine palmitoyltransferase II Beta oxidation/Mitochondrial trifunctional protein: Acyl CoA dehydrogenase ACADL, ACADM, ACADS, ACADVL - Enoyl-CoA hydratase - 3-Hydroxyacyl CoA dehydrogenase - Acetyl-CoA C-acyltransferase to acetyl-CoA: Malonyl-CoA decarboxylase unsaturated Enoyl CoA isomerase, 2,4 Dienoyl-CoA reductase odd chain Propionyl-CoA carboxylase aldehydes Long-chain-aldehyde dehydrogenase see also disorders Retrieved from http://en..org/wiki/Acetyl-CoA_carboxylase Categories: Genes on chromosome 17 | Genes on chromosome 12 | EC 6.4.1Hidden category: Protein pages needing a picture Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages 中文 This page was last modified on 10 June 2008, at 20:17
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