Selective modulation of carnitine long-chain acyltransferase activities - Kinetics, inhibitors, and active sites of COT and CPT-II

R R Ramsay, R D Gandour

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Carnitine acyltransferases in mitochondria, peroxisomes and the endoplasmic reticulum are different gene products and serve different metabolic functions in the cell. Here we summarize briefly evidence that carnitine octanoyltransferase (COT) from the peroxisomes and carnitine palmitoyltransferase II (CPT-II) from the mitochondria (both matrix facing enzymes) differ kinetically and demonstrate that they differ in their sensitivity to conformationally constrained inhibitors that mimic the reaction intermediate. Medium chain inhibitors are 15 times more effective on COT than on CPT-II and long chain inhibitors, such as hemipalmitoylcarnitinium, 80 times more effective on the mitochondrial enzyme. Thus, it may be possible to develop inhibitors to inhibit mitochondrial -beta-oxidation with minimal effects on peroxisomal beta-oxidation and other acyl-CoA dependent reactions.

Original languageEnglish
Title of host publicationCurrent Views of Fatty Acid Oxidation and Ketogenesis: from Organelles to Point Mutations [proceedings of the 4th Fatty Acid Oxidation and Ketogenesis Conference, held April 3-6, 1998, in London, England]
EditorsP. A. Quant, S. Eaton
PublisherSpringer
Pages103-109
Number of pages7
ISBN (Print)0-306-46200-1
DOIs
Publication statusPublished - 1999

Publication series

NameAdvances in Experimental Medicine and Biology
Volume466
ISSN (Print)0065-2598

Keywords

  • FATTY-ACID OXIDATION
  • MALONYL-COA
  • RAT-LIVER
  • PALMITOYLTRANSFERASE ACTIVITY
  • OCTANOYLTRANSFERASE
  • ACETYLTRANSFERASE
  • PURIFICATION
  • MITOCHONDRIA
  • INVIVO

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