Peroxisomal activation of long- and very long-chain fatty acids in the yeast Pichia pastoris.

Abstract

In mammals, beta-oxidation of very long-chain fatty acids (VLCFA) takes place in peroxisomes. This process is impaired in X-linked adrenoleukodystrophy (XALD) patients as a result of decreased activity of peroxisomal very long-chain acyl-CoA synthetase (VLCS). We investigated VLCFA and long chain fatty acid (LCFA) activation in the yeast Pichia pastoris. Both VLCFA and LCFA were activated to their CoA derivatives in an organelle fraction. When organelles were fractionated on a sucrose gradient, VLCS activity co-localized with peroxisomes while long chain acyl-CoA synthetase activity associated primarily with mitochondria. Consistent with these findings, only VLCS activity was reduced in organelle fractions from peroxisome assembly (pas) mutants. Furthermore, no VLCS activity was detected in pas mutants at the density of normal peroxisomes. Thus, we conclude that VLCS is a peroxisomal enzyme in P. pastoris and this organism may serve as an excellent model system to investigate the molecular basis of XALD.

• Authors: J E Kalish, C I Chen, S J Gould, P A Watkins
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 206 Issue 1 Pg. 335-40 (Jan 05 1995) ISSN: 0006-291X [Print] United States
• PMID: 7818538 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Fatty Acids, Nonesterified
• Repressor Proteins
• Saccharomyces cerevisiae Proteins
• Ligases
• Carbon-Sulfur Ligases
• Coenzyme A Ligases
• long-chain-fatty-acid-(acyl-carrier-protein) ligase
• FAA2 protein, S cerevisiae
• long-chain-fatty-acid-CoA ligase

Topics

• Adrenoleukodystrophy (genetics, metabolism)
• Carbon-Sulfur Ligases
• Cell Fractionation
• Centrifugation, Density Gradient
• Coenzyme A Ligases (isolation & purification, metabolism)
• Fatty Acids, Nonesterified (metabolism)
• Genes, Fungal
• Humans
• Ligases (isolation & purification, metabolism)
• Microbodies (metabolism)
• Mutation
• Pichia (enzymology, genetics, metabolism)
• Repressor Proteins
• Saccharomyces cerevisiae Proteins