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.