The metabolic role of human ADH3 functioning as ethanol dehydrogenase.
paper
Cited
Public
Unavailable
- Authors
- Lee, Shou-Lun; Wang, Ming-Fang; Lee, An-I; Yin, Shih-Jiun
- Year
- 2003
- Journal
- FEBS letters
- PMID
- 12782305
- DOI
- 10.1016/s0014-5793(03)00492-7
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 x 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.
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| Title | Year | PMID |
|---|---|---|
| Genes encoding enzymes involved in ethanol metabolism. | 2012 | 23134050 |
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