Cloning, sequencing, and regulation of rat liver carnitine octanoyltransferase: transcriptional stimulation of the enzyme during peroxisome proliferation

Abstract

Several complementary DNAs for the peroxisomal enzyme carnitine octanoyltransferase (COT), cloned in the expression vector lambda gt11, have been isolated. Together, these clones cover 2143 bp of the COT cDNA sequence with an open reading frame for 523 amino acids. Northern analysis showed the mRNA size for this enzyme to be 3.5 kilobases. The 523 residue long amino acid sequence amounts to a molecular mass of 60,269 daltons, indicating that the cloned cDNAs contain most or all of the coding sequence for COT (Mr approximately 62,000). Hybridization studies showed that the increased COT activity in the liver of rats, fed the potent peroxisome-proliferating drug Wy-14,643, is associated with a more than 40-fold rise in the steady-state level of the COT mRNA.