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

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Lipids

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 ω-position of the carbon chain are suitable derivatives for the in vivo investigation of patients with defects in peroxisomal β-oxidation because they are metabolized by the same pathways as the corresponding n-VLCFA. Moreover, as iso-VLCFA and their β-oxidation products are readily separated from the corresponding n-fatty acids by normal chromatographic procedures, the turnover of VLCFA can be more precisely measured.

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Abbreviations

ALD:

adrenoleukodystrophy

BME:

basal Eagle’s medium

iso-fatty acids:

fatty acids with a methyl branch at the ω-2 position

iso-lignoceric acid, iso-24∶0:

22-methyl tricosanoic acid

lignoceric acid:

24∶0, tetracosanoic acid

n-fatty acids:

straight chain fatty acids

VLCFA:

fatty acids with greater than 22 carbon atoms

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Author notes

  1. Alfred Poulos

    Present address: BioMed Technology, 11 Brigalow Ave., 5068, Kensington Gardens, South Australia, Australia

  2. Peter C. Stockham

    Present address: South Australian Water Corporation, Hodgson Rd., 5110, Bolivar, South Australia, Australia

Authors and Affiliations

  1. Department of Chemical Pathology, Women’s and Children’s Hospital, 72 King William Rd., 5006, North Adelaide, South Australia, Australia

    Alfred Poulos, Peter C. Stockham, David W. Johnson, Barbara C. Paton, Kaye Beckman & Harmeet Singh

Authors
  1. Alfred Poulos
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  2. Peter C. Stockham
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  3. David W. Johnson
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  4. Barbara C. Paton
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  5. Kaye Beckman
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  6. Harmeet Singh
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Corresponding author

Correspondence to Barbara C. Paton.

Additional information

A preliminary report of part of this work (Reference 18) was presented at the 5th International Symposium on the Synthesis and Applications of Isotopes and Isotopically Labelled Compounds, Strasbourg, France, June 20–24, 1994.

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Poulos, A., Stockham, P.C., Johnson, D.W. et al. Metabolism of trideuterated iso-lignoceric acid in rats in Vivo and in human fibroblasts in culture. Lipids 34, 943–949 (1999). https://doi.org/10.1007/s11745-999-0444-y

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  • DOI: https://doi.org/10.1007/s11745-999-0444-y

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