Cloning of Human Acetyl-CoA carboxylase-$\beta $ and Its Unique Features

Acetyl-CoA carboxylase, which has a molecular mass of 265 kDa (ACC-$\alpha $), catalyzes the rate-limiting step in the biosynthesis of long-chain fatty acids. In this study we report the complete amino acid sequence and unique features of an isoform of ACC with a molecular mass of 275 kDa (ACC-$\beta $), which is primarily expressed in heart and skeletal muscles. In these tissues, ACC-$\beta $ may be involved in the regulation of fatty acid oxidation, rather than fatty acid biosynthesis. ACC-$\beta $ contains an amino acid sequence at the N terminus which is about 200 amino acids long and may be uniquely related to the role of ACC-$\beta $ in controlling carnitine palmitoyltransferase I activity and fatty acid oxidation by mitochondria. If we exclude this unique sequence at the N terminus the two forms of ACC show about 75% amino acid identity. All of the known functional domains of ACC are found in the homologous regions. Human ACC-$\beta $ cDNA has an open reading frame of 7,343 bases, encoding a protein of 2,458 amino acids, with a calculated molecular mass of 276,638 Da. The mRNA size of human ACC-$\beta $ is approximately 10 kb and is primarily expressed in heart and skeletal muscle tissues, whereas ACC-$\alpha $ mRNA is detected in all tissues tested. A fragment of ACC-$\beta $ cDNA was expressed in Escherichia coli and antibodies against the peptide were generated to establish that the cDNA sequence that we cloned is that for ACC-$\beta $.