Human class I alcohol dehydrogenases catalyze the oxidation of glycols in the metabolism of norepinephrine.
Investigations of the function of human liver alcohol dehydrogenase (ADH) in norepinephrine metabolism have revealed that class I ADH catalyzes the oxidation of the intermediary alcohols 4-hydroxy-3-methoxyphenyl glycol (HMPG) and 3,4-dihydroxyphenyl glycol (DHPG) in vitro. The kcat/Km values for the individual homogeneous class I isozymes are generally in the range from 2.0 to 10 mM-1 X min-1, slightly lower than those obtained for ethanol oxidation, 16-66 mM-1 X min-1, but considerably higher than those obtained for ethylene glycol oxidation, 0.23-1.5 mM-1 X min-1. Importantly, HMPG and DHPG are not substrates for the class II or class III ADHs. 4-Methylpyrazole and 1,10-phenanthroline inhibit the class I ADH-catalyzed oxidation of HMPG, DHPG, and ethanol with inhibition constants of 75-90 nM and 19-22 microM, respectively, indicating that these substrates interact at the same catalytic site of ADH. Moreover, ethanol inhibits the oxidation of HMPG. The competition of ethanol with HMPG for ADH provides a basis for the in vivo changes observed in norepinephrine metabolism after acute ethanol intake. Any assessment of norepinephrine function through the study of metabolites in peripheral body fluid must include monitoring the oxidation of HMPG by ADH.
Mårdh
G
G
Luehr
C A
CA
Vallee
B L
BL
D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077604:Fomepizole; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D013379:Substrate Specificity
D007527:Isoenzymes; D011720:Pyrazoles; D008734:Methoxyhydroxyphenylglycol; D000077604:Fomepizole; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine