MitoSciences: Mitochondrial trifunctional protein (TFP) (HADHA / HADHB)

UniProt Number:	P40939 & P55084
Alternate Names:	mitochondrial trifunctional enzyme subunit alpha and mitochondrial trifunctional enzyme subunit beta, Long-chain enoyl-CoA hydratase, Long chain 3-hydroxyacyl-CoA dehydrogenase, 3-ketoacyl-CoA thiolase
Structure and Function:	TFP is part of the mitochondrial fatty acid beta-oxidation pathway. It is located in the inner mitochondrial membrane and it catalyzes three out of the four steps in the beta-oxidation cycle with a specific affinity for long chain substrates. TFP is hetero-octamer composed of four alpha and four beta subunits. The alpha subunit is a 79 kDa enzyme which has two enzymatic functions, the hydration of enoyl-CoA and the dehydrogenation of 3-hydroxyacyl CoA. The beta subunit, a 47 kDa enzyme, performs the third function - the thiolytic cleavage of 3-ketoacyl-CoA substrates.
Disease Associations:	Defects in HADHA / HADHB are a cause of trifunctional protein deficiency (TFP deficiency) [MIM:609015]. Defects in HADHA are the cause of long-chain 3-hydroxyl-CoA dehydrogenase deficiency (LCHAD deficiency) [MIM:609016]. Defects in HADHA are also a cause of maternal acute fatty liver of pregnancy (AFLP) [MIM:609016]. AFLP is a severe maternal illness occurring during pregnancies with affected fetuses.