Very long chain fatty acid beta-oxidation by subcellular fractions of normal and Zellweger syndrome skin fibroblasts.
Very long chain fatty acid (VLCFA) beta-oxidation was compared in homogenates and subcellular fractions of cultured skin fibroblasts from normal individuals and from Zellweger patients who show greatly reduced numbers of peroxisomes in their tissues. beta-Oxidation of lignoceric (C24:0) acid was greatly reduced compared to controls in the homogenates and the subcellular fractions of Zellweger fibroblasts. The specific activity of C24:0 acid beta-oxidation was highest in the crude peroxisomal pellets of control fibroblasts. Fractionation of the crude mitochondrial and the crude peroxisomal pellets on Percoll density gradients revealed that the C24:0 acid oxidation was carried out entirely by peroxisomes, and the peroxisomal beta-oxidation activity was missing in Zellweger fibroblasts. In contrast to the beta-oxidation of C24:0 acid, the beta-oxidation of C24:0 CoA was observed in both mitochondria and peroxisomes. We postulate that a very long chain fatty acyl CoA (VLCFA CoA) synthetase, which is different from long chain fatty acyl CoA synthetase, is required for the effective conversion of C24:0 acid to C24:0 CoA. The VLCFA CoA synthetase appears to be absent from the mitochondrial membrane but present in the peroxisomal membrane.
Singh
H
H
Department of Chemical Pathology, Adelaide Children's Hospital, South Australia.
Derwas
N
N
Poulos
A
A
D000015:Abnormalities, Multiple; D002460:Cell Line; D002478:Cells, Cultured; D003066:Coenzyme A Ligases / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D010084:Oxidation-Reduction; D012016:Reference Values; D012867:Skin / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D013577:Syndrome
D005227:Fatty Acids; D003066:Coenzyme A Ligases; C044125:lignoceroyl-CoA ligase; C010210:lignoceric acid