Rat heart expresses two forms of mitochondrial carnitine palmitoyltransferase I

Brian C. Weis, Victoria Esser, Daniel W. Foster, J. Denis McGarry

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

Abstract

To begin to explore the basis for the tissue-specific expression of mitochondrial carnitine palmitoyltransferase I (CPT I), we focused on three rat tissues (liver, heart, and skeletal muscle) in which the enzyme was known to display very different properties. In Northern blot analysis, a cDNA probe corresponding to liver CPT I readily hybridized to a 4.5-kilobase species of mRNA in liver and heart, but not in skeletal muscle. Using the same probe to screen a neonatal rat heart cDNA library, a full-length clone, surprisingly having 100% sequence identity to the liver CPT I cDNA, was isolated. The paradox was resolved by two additional experiments. First, in Western blots of mitochondrial membranes, an antibody raised against liver CPT I recognized the 88-kDa protein in heart, as well as in liver, but not in skeletal muscle. Second, high specific activity [3H]deschloroetomoxir (a covalent ligand for CPT I) reacted with a single form of CPT I in liver (~88 kDa) and skeletal muscle (~82 kDa), while proteins of both sizes were labeled in the cardiac myocyte. Tritiated ligand binding to the two heart proteins was blocked by excess unlabeled malonyl-CoA. It is concluded that liver and skeletal muscle each contains a single and distinct isoform of CPT I with monomeric size of ~88 and 82 kDa, respectively. The heart contains a CPT I protein of ~82 kDa in size (probably identical to the skeletal muscle protein) but, importantly, also expresses the liver-type enzyme. The results likely explain why previous studies of heart CPT I yielded an apparent K(m) for carnitine and I60 value for malonyl-CoA inhibition that were intermediate between those of the liver and skeletal muscle enzymes.

Original languageEnglish (US)
Pages (from-to)18712-18715
Number of pages4
JournalJournal of Biological Chemistry
Volume269
Issue number29
StatePublished - 1994

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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