ACETYL COA CARBOXYLASE: ISOFORMS AND REGULATION

Malonyl-CoA is the C₂ donor in the de novo synthesis of fatty acids, and it plays an important role as an inhibitor of the carnitine palmitoyl shuttle system for fatty acid oxidation. Acetyl CoA carboxylase is the enzyme that is responsible for carboxylation of acetyl CoA to malonyl CoA. 

Two different isoforms of acetyl CoA carboxylase exists, i.e. ACC1 and ACC2. ACC1 and ACC2 are encoded by two separate genes localized at chromosome 17q12 and 12q23, respectively. The amino acid sequences of ACC1 and ACC2 are approximately 80% identical.

 ACC1 is a multifunctional enzyme encoded by a single gene. ACC1 is composed of three distinct functional units: biotin carboxylase, biotin carboxyl carrier protein, transcarboxylase. In presence of ATP, biotin carboxylase transfers CO2 from bicarbonate to the biotin carboxyl carrier protein, forming the carboxybiotin derivative. The transcarboxylase catalyzes the transfer of the carboxylase group to acetyl CoA forming Malonyl CoA. ACC1 is generally expressed in all tissues, it is expressed in more lipogenic tissues such as liver, adipose, and lactating mammary gland.

 In contrast, ACC2 is highly expressed in heart, muscle and to a lesser extent in the liver. ACC1 derived malonyl-CoA is utilized by FAS for the synthesis of fatty acids in the cytosol. In contrast, the ACC2-generated malonyl CoA functions as an inhibitor of the carnitine/palmityl transferase 1 activity and the transfer of the fatty acyl group through CPT shuttle to inside the mitochondria for beta-oxidation.