Acetyl-CoA carboxylase

Acetyl-CoA carboxylase

Biotin carboxylase structure

Biotin carboxyl carrier protein

Carboxytransferase structure

Mechanism of acetyl-CoA carboxylase

Regulation of acetyl-CoA carboxylase

Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme that catalyzes the carboxylation of acetyl-CoA to form malonyl-CoA. This reaction is the first committed step in fatty acid synthesis and is a key regulatory point in the metabolic pathway.

Structure

Acetyl-CoA carboxylase is a multi-domain enzyme that consists of three main functional components: the biotin carboxylase (BC) domain, the biotin carboxyl carrier protein (BCCP) domain, and the carboxytransferase (CT) domain. The BC domain catalyzes the ATP-dependent carboxylation of biotin, which is then transferred to the BCCP domain. The CT domain catalyzes the transfer of the carboxyl group from biotin to acetyl-CoA, forming malonyl-CoA.

Function

The primary function of acetyl-CoA carboxylase is to provide malonyl-CoA for the synthesis of long-chain fatty acids. Malonyl-CoA is also an important regulator of fatty acid oxidation, as it inhibits carnitine palmitoyltransferase I (CPT1), the enzyme responsible for transporting fatty acids into the mitochondria for oxidation.

Regulation

Acetyl-CoA carboxylase is regulated by multiple mechanisms, including allosteric regulation, covalent modification, and changes in gene expression. The enzyme is activated by citrate, which promotes polymerization of the enzyme into its active form, and inhibited by palmitoyl-CoA, which promotes depolymerization. Phosphorylation by AMP-activated protein kinase (AMPK) and other kinases inactivates ACC, while dephosphorylation by protein phosphatases activates it.

Clinical significance

Dysregulation of acetyl-CoA carboxylase activity is associated with metabolic disorders such as obesity, type 2 diabetes, and non-alcoholic fatty liver disease. Inhibitors of ACC are being investigated as potential therapeutic agents for these conditions.

Related pages

• Fatty acid synthesis
• Biotin
• AMP-activated protein kinase
• Carnitine palmitoyltransferase I

Gallery

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  Biotin carboxylase structure

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  Biotin carboxyl carrier protein

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  Carboxytransferase structure

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  Mechanism of acetyl-CoA carboxylase

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  Regulation of acetyl-CoA carboxylase

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  Biotin carboxylase structure

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  Biotin carboxyl carrier protein (BCCP)

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  Carboxytransferase from E. coli

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  Acetyl-CoA carboxylase mechanism

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  Control of Acetyl-CoA carboxylase