Complementation analysis of fibroblasts from peroxisomal fatty acid oxidation deficient patients shows high frequency of bifunctional enzyme deficiency plus intragenic complementation: unequivocal evidence for differential defects in the same enzyme protein

Biochem Biophys Res Commun. 1997 Jun 9;235(1):176-9. doi: 10.1006/bbrc.1997.6755.

Abstract

In the last few years many patients have been reported with a defect in peroxisomal fatty acid beta-oxidation of unknown origin. Using a combined approach based on direct activity measurements of straight-chain acyl-CoA oxidase and complementation analysis after somatic cell fusion of fibroblasts, we have now classified 13 patients into 4 distinct groups representing different gene defects. Remarkably, we found intragenic complementation in group 2 so that group 2 is in fact made up of 3 distinct subgroups. The underlying basis for this peculiar phenomenon probably has to do with the fact that bifunctional protein harbors two catalytic activities including enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase. In group 2A enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase are defective whereas in group 2B and 2C either the hydratase or 3-hydroxyacyl-CoA dehydrogenase component of the bifunctional protein is deficient.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxyacyl CoA Dehydrogenases / deficiency*
  • 3-Hydroxyacyl CoA Dehydrogenases / genetics*
  • Cell Fusion
  • Cell Line
  • Enoyl-CoA Hydratase / deficiency*
  • Enoyl-CoA Hydratase / genetics*
  • Fatty Acids / blood
  • Fatty Acids / metabolism
  • Fibroblasts
  • Genetic Complementation Test
  • Humans
  • Isomerases*
  • Multienzyme Complexes / deficiency*
  • Multienzyme Complexes / genetics*
  • Oxidation-Reduction
  • Peroxisomal Bifunctional Enzyme
  • Peroxisomal Disorders / enzymology*
  • Peroxisomal Disorders / genetics
  • Zellweger Syndrome

Substances

  • Fatty Acids
  • Multienzyme Complexes
  • pristanic acid
  • 3-Hydroxyacyl CoA Dehydrogenases
  • EHHADH protein, human
  • Enoyl-CoA Hydratase
  • Peroxisomal Bifunctional Enzyme
  • Isomerases