In:
FEBS Letters, Wiley, Vol. 544, No. 1-3 ( 2003-06-05), p. 143-147
Abstract:
Human class III alcohol dehydrogenase (ADH3), also known as glutathione‐dependent formaldehyde dehydrogenase, exhibited non‐hyperbolic kinetics with ethanol at a near physiological pH 7.5. The S 0.5 and k cat were determined to be 3.4±0.3 M and 33±3 min −1 , and the Hill coefficient ( h ) 2.21±0.09, indicating positive cooperativity. Strikingly, the S 0.5 for ethanol was found to be 5.4×10 6 ‐fold higher than the K m for S ‐(hydroxymethyl)glutathione, a classic substrate for the enzyme, whereas the k cat for the former was 41% lower than that for the latter. Isotope effects on enzyme activity suggest that hydride transfer may be rate‐limiting in the oxidation of ethanol. Kinetic simulations using the experimentally determined Hill constant suggest that gastric ADH3 may highly effectively contribute to the first‐pass metabolism at 0.5–3 M ethanol, an attainable range in the gastric lumen during alcohol consumption. The positive cooperativity mainly accounts for this metabolic role of ADH3.
Type of Medium:
Online Resource
ISSN:
0014-5793
,
1873-3468
DOI:
10.1016/S0014-5793(03)00492-7
Language:
English
Publisher:
Wiley
Publication Date:
2003
detail.hit.zdb_id:
1460391-3
SSG:
12
Permalink