ACACB

Acetyl-CoA carboxylase (ACC) is a complex multifunctional enzyme system. ACC is a biotin-containing enzyme which catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis. ACC-beta is thought to control fatty acid oxidation by means of the ability of malonyl-CoA to inhibit carnitine-palmitoyl-CoA transferase I, the rate-limiting step in fatty acid uptake and oxidation by mitochondria. ACC-beta may be involved in the regulation of fatty acid oxidation, rather than fatty acid biosynthesis. There is evidence for the presence of two ACC-beta isoforms.

Full Name

Acetyl-CoA Carboxylase Beta

Function

Mitochondrial enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA and plays a central role in fatty acid metabolism. Catalyzes a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA. Through the production of malonyl-CoA that allosterically inhibits carnitine palmitoyltransferase 1 at the mitochondria, negatively regulates fatty acid oxidation (By similarity). Together with its cytosolic isozyme ACACA, which is involved in de novo fatty acid biosynthesis, promotes lipid storage (By similarity).

Biological Process

Acetyl-CoA metabolic process
Carnitine shuttle
Energy homeostasis
Fatty acid biosynthetic process
Malonyl-CoA biosynthetic process
Negative regulation of catalytic activity
Negative regulation of fatty acid beta-oxidation
Negative regulation of gene expression
Positive regulation of cellular metabolic process
Positive regulation of heart growth
Positive regulation of lipid storage
Protein homotetramerization
Regulation of glucose metabolic process
Regulation of lipid metabolic process
Response to drug
Response to nutrient levels
Response to organic cyclic compound

Cellular Location

Mitochondrion

PTM

The biotin cofactor is covalently attached to the central biotinyl-binding domain and is required for the catalytic activity.
Phosphorylation at Ser-222 by AMPK inactivates the enzyme. Required for the maintenance of skeletal muscle lipid and glucose homeostasis (By similarity).