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Acetyl-CoA 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

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 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.

 

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

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. 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
Lipid productionAcetyl-CoA carboxylase - Fatty acid synthesis: Beta-ketoacyl-ACP synthase - Β-Ketoacyl ACP reductase - 3-Hydroxyacyl ACP dehydrase - Enoyl ACP reductase
unsaturated (Enoyl CoA isomerase, 2,4 Dienoyl-CoA reductase) - odd chain (Propionyl-CoA carboxylase) - Fatty acid synthase - Long fatty acyl CoA synthetase
Lipid degradationAcyl transport: Carnitine palmitoyltransferase I - Carnitine-acylcarnitine translocase - Carnitine palmitoyltransferase II
Beta oxidation: Acyl CoA dehydrogenase (ACADL, ACADM, ACADS, ACADVL) - Enoyl-CoA hydratase - 3-Hydroxyacyl CoA dehydrogenase - Acetyl-CoA C-acyltransferase - Mitochondrial trifunctional protein
Ketogenesis: HMG-CoA synthase - HMG-CoA lyase - Other: Malonyl-CoA decarboxylase
PhospholipidsDiacylglycerol kinase
SteroidsHMG-CoA reductase - Farnesyl-diphosphate farnesyltransferase - Squalene monooxygenase - Lanosterol synthase - CYP51A1
ProstanoidsCyclooxygenase - Thromboxane-A synthase - Prostacyclin synthase - Prostaglandin E synthase - Prostaglandin D2 synthase
LeukotrienesArachidonate 5-lipoxygenase - 5-Lipoxygenase activating protein - Leukotriene A4 hydrolase - Leukotriene C4 synthase
Bile acidsCholesterol 7 alpha-hydroxylase
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Acetyl-CoA_carboxylase". A list of authors is available in Wikipedia.
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