The mitochondrial trifunctional protein: centre of a beta-oxidation metabolon?
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'.
Eaton
S
S
Unit of Paediatric Surgery, Institute of Child Health, London, UK.
Bursby
T
T
Middleton
B
B
Pourfarzam
M
M
Mills
K
K
Johnson
A W
AW
Bartlett
K
K
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
D009097:Multienzyme Complexes; D063991:Mitochondrial Trifunctional Protein; D010100:Oxygen