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Acetyl-CoA carboxylase: Wikis


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Human Acetyl-Coenzyme A carboxylase alpha
Symbol ACACA
Alt. symbols ACAC, ACC1, ACCA
Entrez 31
OMIM 601557
RefSeq NM_198839
UniProt Q13085
Other data
EC number
Locus Chr. 17 q21
Human Acetyl-Coenzyme A carboxylase beta
Symbol ACACB
Alt. symbols ACC2, ACCB
Entrez 32
OMIM 200350
RefSeq NM_001093
UniProt O00763
Other data
EC number
Locus Chr. 12 q24.1

Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme that catalyzes the irreversible carboxylation of acetyl-CoA to produce malonyl-CoA through its two catalytic activities, biotin carboxylase (BC) and carboxyltransferase (CT). ACC is a multi-subunit enzyme in most prokaryotes and in the chloroplasts of most plants and algae, whereas it is a large, multi-domain enzyme in the endoplasmic reticulum of most eukaryotes. The most important function of ACC is to provide the malonyl-CoA substrate for the biosynthesis of fatty acids.[1] The activity of ACC can be controlled at the transcriptional level as well as by small molecule modulators and covalent modification. The human genome contains the genes for two different ACCs[2] — ACACA[3] and ACACB.[4] In muscle cells, malonyl-CoA inhibits beta-oxidation.



ACACA (2346 aa) and ACACB (2483 aa) have four functional regions each, starting from the N-terminus to C-terminus: biotin carboxylating (BC), biotin binding (BB), carboxyltransferase (CT), and ATP-binding (AB). AB 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 both of the active sites where it is required.


The overall reaction of ACAC(A,B) proceeds by a two-step mechanism.[5] The first 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 reaction, which is catalyzed by CT.

The reaction mechanism of ACAC(A,B).
The color scheme is as follows: enzyme, coenzymes, substrate names, metal ions, phosphate, and carbonate


In muscle cells, the function of ACAC is to regulate the metabolism of fatty acids. When the enzyme is active, the product, malonyl-CoA is produced and inhibits the transfer of the fatty acyl group from acyl CoA to carnitine with carnitine acyltransferase, which inhibits the beta-oxidation of fatty acids in the mitochondria.


Control of Acetyl CoA Carboxylase.

The regulation of acetyl-CoA carboxylase is complex and is responsive to nutritional status and hormones.

The inactive dimer form of this enzyme is induced to polymerize by citrate, yielding the active polymer form. The activity of the enzyme is also controlled by reversible phosphorylation. The enzyme is inhibited if phosphorylated; the phosphorylation can result when the hormones glucagon or epinephrine bind to their receptors, but the main cause of phosphorylation is due to a rise in AMP levels when the energy status of the cell is low, leading to the activation of the AMP-activated protein kinase [6].

The presence of fatty acid inhibits the enzyme.

When insulin binds to its receptors on the cellular membrane, it activates a phosphatase to dephosphorylate the enzyme; thereby removing the inhibitory effect.

The arrows on this image are backwards. The AMP regulated kinase triggers the phorphorylation of the enzyme (thus inactivating it) and the phosphatase eynzyme removes the phosphate group.

Clinical implications

Bacterial Acetyl-CoA carboxylase has recently become a target in the design of new anti-obesity and antibiotic drugs.[7]

See also


  1. ^ Tong L (August 2005). "Acetyl-coenzyme A carboxylase: crucial metabolic enzyme and attractive target for drug discovery". Cell. Mol. Life Sci. 62 (16): 1784–803. doi:10.1007/s00018-005-5121-4. PMID 15968460. 
  2. ^ Brownsey RW, Zhande R, Boone AN (November 1997). "Isoforms of acetyl-CoA carboxylase: structures, regulatory properties and metabolic functions". Biochem. Soc. Trans. 25 (4): 1232–8. PMID 9449982. 
  3. ^ Abu-Elheiga L, Jayakumar A, Baldini A, Chirala SS, Wakil SJ (April 1995). "Human acetyl-CoA carboxylase: characterization, molecular cloning, and evidence for two isoforms". Proc. Natl. Acad. Sci. U.S.A. 92 (9): 4011–5. doi:10.1073/pnas.92.9.4011. PMID 7732023. 
  4. ^ Widmer J, Fassihi KS, Schlichter SC, Wheeler KS, Crute BE, King N, Nutile-McMenemy N, Noll WW, Daniel S, Ha J, Kim KH, Witters LA (June 1996). "Identification of a second human acetyl-CoA carboxylase gene". Biochem. J. 316 ( Pt 3): 915–22. PMID 8670171. PMC 1217437. 
  5. ^ Lee CK, Cheong HK, Ryu KS, Lee JI, Lee W, Jeon YH, Cheong C (August 2008). "Biotinoyl domain of human acetyl-CoA carboxylase: Structural insights into the carboxyl transfer mechanism". Proteins 72 (2): 613–24. doi:10.1002/prot.21952. PMID 18247344. 
  6. ^ Brownsey RW, Boone AN, Elliott JE, Kulpa JE, Lee WM (April 2006). "Regulation of acetyl-CoA carboxylase". Biochem. Soc. Trans. 34 (Pt 2): 223–7. doi:10.1042/BST20060223. PMID 16545081. 
  7. ^ Corbett JW, Harwood JH (November 2007). "Inhibitors of mammalian acetyl-CoA carboxylase". Recent Patents Cardiovasc Drug Discov 2 (3): 162–80. doi:10.2174/157489007782418928. PMID 18221116. 

Further reading

  • Voet, Donald; Voet, Judith G. (2004). Biochemistry (3rd ed.). Wiley. ISBN 0-471-19350-x. 
  • edited by (2000). Buchanan, Bob B.; Gruissem, Wilhelm; Jones, Russell L.. eds. Biochemistry and molecular biology of plants. American Society of Plant Physiologists. ISBN 0-943088-37-2. 
  • 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. 


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