Mårdh G, Vallee B L
Biochemistry. 1986 Nov 18;25(23):7279-82. doi: 10.1021/bi00371a005.
The class I human liver alcohol dehydrogenases (ADHs) catalyze the interconversion of the intermediary alcohols and aldehydes of dopamine metabolism in vitro, whereas those of the class II and class III do not. The individual, homogeneous class I isozymes oxidize (3,4-dihydroxyphenyl)ethanol and (4-hydroxy-3-methoxyphenyl)ethanol (HMPE) and ethanol with kcat/Km values in the range from 16 to 240 mM-1 min-1 and from 16 to 66 mM-1 min-1, respectively. They reduce the corresponding dopamine aldehydes (3,4-dihydroxyphenyl)acetaldehyde and (4-hydroxy-3-methoxyphenyl)acetaldehyde (HMPAL) with kcat/Km values varying from 7800 to 190,000 mM-1 min-1, considerably more efficient than the reduction of acetaldehyde with kcat/Km values from 780 to 4900 mM-1 min-1. For beta 1 gamma 2 ADH, ethanol competes with HMPE oxidation with a Ki of 23 microM. In addition, 1,10-phenanthroline inhibits HMPE oxidation and HMPAL reduction with Ki values of 20 microM and 12 microM, respectively, both quite similar to that for ethanol, Ki = 22 microM. Thus, both ethanol/acetaldehyde and the dopamine intermediates compete for the same site of ADH, a basis for the ethanol-induced in vivo alterations of dopamine metabolism.
I类人肝脏乙醇脱氢酶（ADHs）在体外催化多巴胺代谢中间产物醇类和醛类的相互转化，而II类和III类则不能。单一的、均一的I类同工酶氧化（3,4 - 二羟基苯基）乙醇和（4 - 羟基 - 3 - 甲氧基苯基）乙醇（HMPE）以及乙醇，其催化常数与米氏常数的比值（kcat/Km）分别在16至240 mM-1 min-1和16至66 mM-1 min-1范围内。它们还原相应的多巴胺醛类（3,4 - 二羟基苯基）乙醛和（4 - 羟基 - 3 - 甲氧基苯基）乙醛（HMPAL），kcat/Km值在7800至190,000 mM-1 min-1之间，比还原乙醛（kcat/Km值为780至4900 mM-1 min-1）效率高得多。对于β1γ2 ADH，乙醇与HMPE氧化竞争，抑制常数（Ki）为23 μM。此外，1,10 - 菲咯啉抑制HMPE氧化和HMPAL还原，Ki值分别为20 μM和12 μM，两者都与乙醇的抑制常数（Ki = 22 μM）非常相似。因此，乙醇/乙醛和多巴胺中间产物都竞争ADH的同一位点，这是乙醇在体内诱导多巴胺代谢改变的基础。
