FEBS Letters | |
The metabolic role of human ADH3 functioning as ethanol dehydrogenase | |
Yin, Shih-Jiun2  Lee, An-I1  Lee, Shou-Lun2  Wang, Ming-Fang1  | |
[1] Department of Biochemistry, National Defense Medical Center, 161 Min-Chuan East Road Section 6, Taipei 114, Taiwan;Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan | |
关键词: Alcohol dehydrogenase; class III; Formaldehyde dehydrogenase; Ethanol dehydrogenase; Kinetic cooperativity; First-pass metabolism; ADH; alcohol dehydrogenase; ADH3; class III ADH; HMGSH; S-(hydroxymethyl)glutathione; FPM; first-pass metabolism; | |
DOI : 10.1016/S0014-5793(03)00492-7 | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
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 5.4×106-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.
【 授权许可】
Unknown
【 预 览 】
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