Identification of muscle-type carnitine palmitoyltransferase I and characterization of its gene structure

Abstract

To characterize energy metabolism in brown adipose tissue (BAT), differential screening of a cDNA library of rat BAT with a cDNA probe of rat white adipose tissue was carried out. We isolated one novel cDNA clone encoding a protein of 88.2 kDa consisting of 772 amino acids. The deduced amino acid sequence showed the highest homology (62.6 %) with that of rat liver carnitine palmitoyltransferase I (CPTI). The transcript corresponding to this cDNA was abundantly expressed not only in BAT but also in the heart and skeletal muscle. CPTI is a protein necessary for the β-oxidation of long-chain fatty acids in mammalian mitochondria, and it has been suggested that at least two isoforms, the liver type and muscle (M-CPTI) type, exist. Based on these observations, we concluded that the novel cDNA clone isolated from rat BAT encodes M-CPTI. Isolation and characterization of a genomic DNA clone revealed that the gene for human M-CPTI consists of two 5′-noncoding exons, 18 coding exons, and one 3′-noncoding exon spanning approximately 10 kbp, and a gene encoding choline/ethanolamine kinase-β (CK/EK-β) was located about 300 bp upstream from the M-CPTI gene with the same strand direction. Furthermore, we found atypical transcripts containing exons of both CK/EK-β and M-CPTI genes in humans and rodents. The physiologic role(s) of these transcripts is still unknown. However, it is interesting that such transcripts are produced from two tightly arranged and functionally unrelated genes in mammalian tissues. © 2004 The Pharmaceutical Society of Japan.