Article

Acetyl-coenzyme A carboxylase: crucial metabolic enzyme and attractive target for drug discovery.

Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
Cellular and Molecular Life Sciences CMLS (impact factor: 6.57). 09/2005; 62(16):1784-803. DOI:10.1007/s00018-005-5121-4 pp.1784-803
Source: PubMed

ABSTRACT Acetyl-coenzyme A carboxylases (ACCs) have crucial roles in fatty acid metabolism in most living organisms. Mice deficient in ACC2 have continuous fatty acid oxidation and reduced body fat and body weight, validating this enzyme as a target for drug development against obesity, diabetes and other symptoms of the metabolic syndrome. ACC is a biotin-dependent enzyme and catalyzes the 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 the enzyme can be controlled at the transcriptional level as well as by small molecule modulators and covalent modification. This review will summarize the structural information that is now available for both the BC and CT enzymes, as well as the molecular mechanism of action of potent ACC inhibitors. The current intense research on these enzymes could lead to the development of novel therapies against metabolic syndrome and other diseases.

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Keywords

ACC
 
biotin carboxylase
 
body fat
 
body weight
 
carboxylases
 
covalent modification
 
CT enzymes
 
current intense research
 
diseases
 
enzymes
 
fatty acid metabolism
 
metabolic syndrome
 
molecular mechanism
 
novel therapies
 
obesity
 
potent ACC inhibitors
 
small molecule modulators
 
structural information
 
transcriptional level
 
two catalytic activities
 

L Tong