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

To characterize energy metabolism in rat brown adipose tissue (BAT), we carried out differential screening of a cDNA library of BAT with a cDNA probe of white adipose tissue and isolated one novel cDNA clone. It contained a single open-reading frame of 2316 bases, which encodes a protein of 88.2 kDa. The predicted amino acid sequence showed the highest homology (62.6%) with that of carnitine palmitoyltransferase I (CPTI) from rat liver. The transcript corresponding to this cDNA was found to be abundantly expressed not only in BAT but also in heart and skeletal muscle. CPTI is known to be a protein necessary for the beta-oxidation of long-chain fatty acids in mammalian mitochondria, and it has been suggested that at least two isoforms, the liver type and muscle type, exist. From these observations, a cDNA clone isolated from rat BAT was concluded to be encoding muscle-type CPTI (M-CPTI). 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-beta (CK/EK-beta) was located only about 300 bp upstream from the M-CPTI gene with the same strand direction. Furthermore, we found that unordinary transcripts containing exons of both CK/EK-beta and M-CPTI genes exist in human and rodent tissues. Although the physiologic role(s) of these transcripts is still unknown, it is interesting that such transcripts are produced from two tightly arranged and functionally unrelated genes.