title: The mitochondrial trifunctional protein: centre of a beta-oxidation metabolon?
abstract: 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'.
authors.affiliation: Unit of Paediatric Surgery, Institute of Child Health, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Eaton
authors.forename: T
authors.initials: T
authors.lastname: Bursby
authors.forename: B
authors.initials: B
authors.lastname: Middleton
authors.forename: M
authors.initials: M
authors.lastname: Pourfarzam
authors.forename: K
authors.initials: K
authors.lastname: Mills
authors.forename: A W
authors.initials: AW
authors.lastname: Johnson
authors.forename: K
authors.initials: K
authors.lastname: Bartlett
mesh_terms: D000595:Amino Acid Sequence; D002384:Catalysis; D006801:Humans; D063991:Mitochondrial Trifunctional Protein; D008954:Models, Biological; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010100:Oxygen / Q000378:metabolism; D017434:Protein Structure, Tertiary
chemical_list: D009097:Multienzyme Complexes; D063991:Mitochondrial Trifunctional Protein; D010100:Oxygen