Xy. He et al., Intrinsic alcohol dehydrogenase and hydroxysteroid dehydrogenase activities of human mitochondrial short-chain L-3-hydroxyacyl-CoA dehydrogenase, BIOCHEM J, 345, 2000, pp. 139-143
The alcohol dehydrogenase (ADH) activity of human short-chain L-3-hydroxyac
yl-CoA dehydrogenase (SCHAD) has been characterized kinetically. The k(cat)
of the purified enzyme was estimated to be 2.2 min(-1), with apparent K-m
values of 280 mM and 22 mu M for 2-propanol and NAD(+), respectively. The k
(cat) of the ADH activity was three orders of magnitude less than the L3-hy
droxyacyl-CoA dehydrogenase activity but was comparable with that of the en
zyme's hydroxysteroid dehydrogenase (HSD) activity for oxidizing 17 beta-oe
stradiol [He, Merz, Mehta, Schulz and Yang(1999) J. Biol. Chem. 274, 15014-
15019]. However, the k(cat) values of intrinsic ADH and HSD activities of h
uman SCHAD were found to be two orders of magnitude less than those reporte
d for endoplasmic-reticulum-associated amyloid beta-peptide-binding protein
(ERAB) [Yan, Shi, Zhu, Fu, Zhu, Zhu, Gibson, Stern, Collison, Al-Mohanna e
t al. (1999) J. Biol, Chem. 274, 2145-2156]. Since human SCHAD and ERAB app
arently possess identical amino acid sequences, their catalytic properties
should be identical. The recombinant SCHAD has been confirmed to be the rig
ht gene product and not a mutant variant. Steady-state kinetic measurements
and quantitative analyses reveal that assay conditions such as pH and conc
entrations of coenzyme and substrate do not account for the kinetic differe
nces reported for ERAB and SCHAD, Rather problematic experimental procedure
s appear to be responsible for the unrealistically high catalytic rate cons
tants of ERAB. Eliminating the confusion surrounding the catalytic properti
es of this important multifunctional enzyme paves the way for exploring its
role(s) in the pathogenesis of Alzheimer's disease.