Peroxisomal β-oxidation and peroxisome proliferator - Activated receptor α: An adaptive metabolic system

J. K. Reddy*, T. Hashimoto

*Corresponding author for this work

Research output: Contribution to journalReview article

652 Scopus citations

Abstract

β-Oxidation occurs in both mitochondria and peroxisomes. Mitochondria catalyze the β-oxidation of the bulk of short-, medium-, and long-chain fatty acids derived from diet, and this pathway constitutes the major process by which fatty acids are oxidized to generate energy. Peroxisomes are involved in the β-oxidation chain shortening of long-chain and very-long-chain fatty acyl-coenzyme (CoAs), long-chain dicarboxylyl-CoAs, the CoA esters of eicosanoids, 2-methyl-branched fatty acyl-CoAs, and the CoA esters of the bile acid intermediates di- and trihydroxycoprostanoic acids, and in the process they generate H2O2. Long-chain and very-long-chain fatty acids (VLCFAs) are also metabolized by the cytochrome P450 CYP4A ω-oxidation system to dicarboxylic acids that serve as substrates for peroxisomal β-oxidation. The peroxisomal β-oxidation system consists of (a) a classical peroxisome proliferator - inducible pathway capable of catalyzing straight-chain acyl-CoAs by fatty acyl-CoA oxidase, L-bifunctional protein, and thiolase, and (b) a second noninducible pathway catalyzing the oxidation of 2-methyl-branched fatty acyl-CoAs by branched-chain acyl-CoA oxidase (pristanoyl-CoA oxidase/trihydroxycoprostanoyl-CoA oxidase), D-bifunctional protein, and sterol carrier protein (SCP)x. The genes encoding the classical β-oxidation pathway in liver are transcriptionally regulated by peroxisome proliferator - activated receptor α (PPARα). Evidence derived from mice deficient in PPARα, peroxisomal fatty acyl-CoA oxidase, and some of the other enzymes of the two peroxisomal β-oxidation pathways points to the critical importance of PPARα and of the classical peroxisomal fatty acyl-CoA oxidase in energy metabolism, and in the development of hepatic steatosis, steatohepatitis, and liver cancer.

Original languageEnglish (US)
Pages (from-to)193-230
Number of pages38
JournalAnnual Review of Nutrition
Volume21
DOIs
StatePublished - 2001

Keywords

  • Fatty acid oxidation
  • Gene knockout models
  • PPARα

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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