Acetyl-CoA carboxylase
From Wikipedia, the free encyclopedia
Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme that catalyses 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, 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.
[edit] StructureACACA (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. [edit] FunctionThe overall reaction of ACAC(A,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. |
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The reaction mechanism of ACAC(A,B).
The color scheme is as follows: enzyme, coenzymes, substrate names, metal ions, phosphate, and carbonate |
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[edit] Clinical implications
Acetyl-CoA carboxylase has recently become a target in the design of new anti-obesity and antibiotic drugs.
[edit] References
- A biotin analog inhibits acetyl-CoA carboxylase activity and adipogenesis. J. Biol. Chem. 2002 May 10, 277(19): 16347-50; Full text
