In cells, excess metabolic fuel is converted into fatty acids in cytosol and oxidized later in mitochondria to generate ATP and acetyl CoA. In fatty acid synthesis, catalytic formation of malonyl CoA from acetyl CoA by Acetyl CoA carboxylase (ACC1) is the rate limiting step. The translocation of LCFA CoA from cytosol to mitochondria is catalyzed by two carnitine palmitoyl transferases (CPT1 and CPT2) and regulated by ACC2, the rate limiting step of mitochondrial fatty acid beta oxidation. Activities of ACC1 and 2 are regulated by their phosphorylation by 5' AMP activated protein kinase (AMPK). Diabetes deranges AMPK master switch and represses the ACC1 gene expression and stimulates excessive fatty acid oxidation which in turn interferes with glucose metabolism. ACC1 is also known as ACC alpha and is a cytosolic enzyme, enriched in liver, adipose, and lactating mammary tissues. ACC1 catalyzes the carboxylation of acetyl CoA to form malonyl CoA, the rate limiting step in the biogenesis of LCFA CoA. ACC1 has three main functions acting as a biotin carboxyl carrier protein, a biotin carboxylase, and a carboxyltransferase (catalytic activity). Two variants of ACC1 have been described. One with 8 additional amino acids commencing at Pro 1196. The other, which is 59aa shorter than the predominant fat and liver isoform, exists in mammals. The presence of 8 additional amino acids inhibits the in vitro phosphorylation of the Ser1200 by cAMP dependent kinase. The two ACC1 isoforms are differentially regulated in a tissue specific manner and under different physiological conditions. The activity of ACC1 is finely regulated by hormone dependent phosphorylation and dephosphorylation.