Structural and functional genomics of the CPT1B gene for muscle-type carnitine palmitoyltransferase I in mammals

Feike R. Van Der Leij, Keith B. Cox*, Vicky N. Jackson, Nicolette C.A. Huijkman, Beatrijs Bartelds, Jaap R.G. Kuipers, Trijnie Dijkhuizen, Peter Terpstra, Philip A. Wood, Victor A. Zammit, Nigel T. Price

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

39 Citations (Scopus)

Abstract

Muscle-type carnitine palmitoyltransferase I (M-CPT I) is a key enzyme in the control of β-oxidation of long-chain fatty acids in the heart and skeletal muscle. Because knowledge of the mammalian genes encoding M-CPT I may aid in studies of disturbed energy metabolism, we obtained new genomic and cDNA data for M-CPT I for the human, mouse, rat, and sheep. The introns of these compact genes are 80% (mouse versus rat) and 60% (mouse versus human) identical. Sheep and goat, but not cow, pig, rodent, or human promoter sequences contain a short interspersed repeated sequence (SINE) upstream of highly conserved regulatory elements. These elements constitute two promoters in humans, sheep, and mice, and, contrary to previous reports, there is a second promoter in rats as well. Thus, the transcriptional organization of these genes is more uniform than previously supposed, with interspecies differences in the 5′-ends of the mRNAs reflecting differences in splicing; only in humans extensive splicing and splice variation is found in the 5′-and 3′-untranslated regions. In the mouse, intron retention was detected in heart, muscle, and testes and may indicate an additional mechanism of regulation of M-CPT I expression. Splice variation in the coding region was previously proposed to lead to expression of CPT I enzymes with altered malonyl-CoA sensitivity (Yu, G. S., Lu, Y. C., and Gulick, T. (1998) Biochem. J. 334, 225-231). However, when expressed in the yeast Pichia pastoris, none of three earlier described splice variants had CPT I activity. Therefore, the involvement of splice variation of M-CPT I in the modulation of malonyl-CoA inhibition of fatty acid oxidation may be less relevant than hitherto assumed.

Original languageEnglish
Pages (from-to)26994-27005
Number of pages12
JournalJournal of Biological Chemistry
Volume277
Issue number30
DOIs
Publication statusPublished - Jul 2002
Externally publishedYes

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