Consalvi V, Mårdh G, Vallee B L
Biochem Biophys Res Commun. 1986 Sep 30;139(3):1009-16. doi: 10.1016/s0006-291x(86)80278-9.
Human liver alcohol dehydrogenases (ADH) may participate in serotonin (5-hydroxytryptamine) metabolism. Class I and II isozymes catalyze the oxidation of 5-hydroxytryptophol (5-HTOL) with kcat/Km values ranging from 10 to 100 mM-1 min-1 compared to 4-66 mM-1 min-1 for that of ethanol at pH 7.40, 25 degrees C. The product, 5-hydroxyindoleacetaldehyde, was purified as its semicarbazone and identified by mass spectrometry. Ethanol competitively inhibits 5-HTOL oxidation by beta 1 gamma 2 ADH with a Ki of 440 microM, a value similar to the Km of ethanol, 210 microM. The inhibition constants for 1,10-phenanthroline and 4-methylpyrazole are 20 microM and 80 nM respectively, essentially identical to those obtained with ethanol as substrate, 22 microM and 70 nM, respectively. The competition between ethanol and 5-HTOL for ADH can explain observations of ethanol induced changes in serotonin metabolism in vivo.
人类肝脏乙醇脱氢酶（ADH）可能参与血清素（5-羟色胺）代谢。I类和II类同工酶催化5-羟色醇（5-HTOL）的氧化反应，在pH 7.40、25℃条件下，其催化常数与米氏常数的比值（kcat/Km）范围为10至100 mM-1 min-1，相比之下乙醇的该比值为4至66 mM-1 min-1。产物5-羟吲哚乙醛以其半卡巴腙形式被纯化，并通过质谱法进行鉴定。乙醇对β1γ2 ADH催化的5-HTOL氧化反应具有竞争性抑制作用，抑制常数（Ki）为440 μM，该值与乙醇的米氏常数（210 μM）相似。1,10-菲咯啉和4-甲基吡唑的抑制常数分别为20 μM和80 nM，与以乙醇作为底物时获得的抑制常数（分别为22 μM和70 nM）基本相同。乙醇和5-HTOL对ADH的竞争作用可以解释体内乙醇诱导血清素代谢变化的相关观察结果。
