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Metabolism of trideuterated iso-lignoceric acid in rats in vivo and in human fibroblasts in culture.

Abstract
Saturated very long chain fatty acids (fatty acids with greater than 22 carbon atoms; VLCFA) accumulate in peroxisomal disorders, but there is little information on their turnover in patients. To determine the suitability of using stable isotope-labeled VLCFA in patients with these disorders, the metabolism of 22-methyl[23,23,23-2H3]tricosanoic (iso-lignoceric) acid was studied in rats in vivo and in human skin fibroblasts in culture. The deuterated iso-VLCFA was degraded to the corresponding 16- and 18-carbon iso-fatty acids by rats in vivo and by normal human skin fibroblasts in culture, but there was little or no degradation in peroxisome-deficient (Zellweger's syndrome) fibroblasts, indicating that its oxidation was peroxisomal. Neither the 14-, 20-, and 22-carbon iso-fatty acids nor the corresponding odd-chain metabolites could be detected. In the rat, the organ containing most of the iso-lignoceric acid, and its breakdown products, was the liver, whereas negligible amounts were detected in the brain, suggesting that little of the fatty acid crossed the blood-brain barrier. Our data indicate that VLCFA labeled with deuterium at the omega-position of the carbon chain are suitable derivatives for the in vivo investigation of patients with defects in peroxisomal beta-oxidation because they are metabolized by the same pathways as the corresponding n-VLCFA. Moreover, as iso-VLCFA and their beta-oxidation products are readily separated from the corresponding n-fatty acids by normal chromatographic procedures, the turnover of VLCFA can be more precisely measured.
AuthorsA Poulos, P C Stockham, D W Johnson, B C Paton, K Beckman, H Singh
JournalLipids (Lipids) Vol. 34 Issue 9 Pg. 943-9 (Sep 1999) ISSN: 0024-4201 [Print] United States
PMID10574659 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Fatty Acids
  • Deuterium
  • lignoceric acid
Topics
  • Animals
  • Blood-Brain Barrier
  • Brain (metabolism)
  • Cells, Cultured
  • Chromatography, Gas
  • Deuterium
  • Fatty Acids (metabolism)
  • Fibroblasts (metabolism)
  • Humans
  • Liver (metabolism)
  • Oxidation-Reduction
  • Peroxisomes (metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Zellweger Syndrome (metabolism)

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