title: Structural and functional genomics of the CPT1B gene for muscle-type carnitine palmitoyltransferase I in mammals.
abstract: Muscle-type carnitine palmitoyltransferase I (M-CPT I) is a key enzyme in the control of beta-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.
authors.affiliation: Department of Pediatrics, Groningen University Institute for Drug Exploration, University of Groningen and Beatrix Children's Hospital, Groningen 9700RB, The Netherlands. f.r.van.der.ley@med.rug.nl
authors.forename: Feike R
authors.initials: FR
authors.lastname: van der Leij
authors.forename: Keith B
authors.initials: KB
authors.lastname: Cox
authors.forename: Vicky N
authors.initials: VN
authors.lastname: Jackson
authors.forename: Nicolette C A
authors.initials: NC
authors.lastname: Huijkman
authors.forename: Beatrijs
authors.initials: B
authors.lastname: Bartelds
authors.forename: Jaap R G
authors.initials: JR
authors.lastname: Kuipers
authors.forename: Trijnie
authors.initials: T
authors.lastname: Dijkhuizen
authors.forename: Peter
authors.initials: P
authors.lastname: Terpstra
authors.forename: Philip A
authors.initials: PA
authors.lastname: Wood
authors.forename: Victor A
authors.initials: VA
authors.lastname: Zammit
authors.forename: Nigel T
authors.initials: NT
authors.lastname: Price
mesh_terms: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism*; D002417:Cattle; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000378:metabolism; D005091:Exons; D006041:Goats; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D011401:Promoter Regions, Genetic; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D012756:Sheep; D012984:Software; D013552:Swine; D014018:Tissue Distribution; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D018076:DNA, Complementary; D002334:Carnitine O-Palmitoyltransferase