The mitochondrial trifunctional protein: centre of a beta-oxidation metabolon?

Biochem Soc Trans. 2000 Feb;28(2):177-82. doi: 10.1042/bst0280177.


The trifunctional enzyme comprises three consecutive steps in the mitochondrial beta-oxidation of long-chain acyl-CoA esters: 2-enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase and 3-ketoacyl-CoA thiolase. Deficiencies in either 3-hydroxyacyl-CoA dehydrogenase activity, or all three activities, are important causes of human disease. The dehydrogenase and thiolase have a requirement for NAD+ and CoA respectively, whose levels are conserved within the mitochondrion and thus provide possible means for control and regulation of beta-oxidation. Using analysis of the intact CoA ester intermediates produced by the complex, we have examined the sensitivity of the complex to NAD+/NADH and acetyl-CoA. We consider the evidence for channelling within the trifunctional protein and propose a model for a beta-oxidation 'metabolon'.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Catalysis
  • Humans
  • Mitochondrial Trifunctional Protein
  • Models, Biological
  • Molecular Sequence Data
  • Multienzyme Complexes / deficiency
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism*
  • Mutation
  • Oxygen / metabolism
  • Protein Structure, Tertiary


  • Multienzyme Complexes
  • Mitochondrial Trifunctional Protein
  • Oxygen