Peroxisomal beta-oxidation and peroxisome proliferator-activated receptor alpha: an adaptive metabolic system

Annu Rev Nutr. 2001;21:193-230. doi: 10.1146/annurev.nutr.21.1.193.


beta-Oxidation occurs in both mitochondria and peroxisomes. Mitochondria catalyze the beta-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 beta-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 omega-oxidation system to dicarboxylic acids that serve as substrates for peroxisomal beta-oxidation. The peroxisomal beta-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 beta-oxidation pathway in liver are transcriptionally regulated by peroxisome proliferator-activated receptor alpha (PPAR alpha). Evidence derived from mice deficient in PPAR alpha, peroxisomal fatty acyl-CoA oxidase, and some of the other enzymes of the two peroxisomal beta-oxidation pathways points to the critical importance of PPAR alpha and of the classical peroxisomal fatty acyl-CoA oxidase in energy metabolism, and in the development of hepatic steatosis, steatohepatitis, and liver cancer.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adaptation, Biological*
  • Animals
  • Energy Metabolism
  • Fatty Acids / metabolism*
  • Fatty Acids, Unsaturated / metabolism
  • Humans
  • Lipid Metabolism, Inborn Errors
  • Mice
  • Microsomes / metabolism
  • Mitochondria / metabolism
  • Oxidation-Reduction
  • Peroxisomes / metabolism*
  • Protein Isoforms
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Transcription Factors / physiology*


  • Fatty Acids
  • Fatty Acids, Unsaturated
  • Protein Isoforms
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors