Human class I alcohol dehydrogenases catalyze the interconversion of alcohols and aldehydes in the metabolism of dopamine

Abstract

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.

Neurotoxicity and Metabolism of the Catecholamine-Derived 3,4-Dihydroxyphenylacetaldehyde and 3,4-Dihydroxyphenylglycolaldehyde: The Role of Aldehyde Dehydrogenase

“…These enzymes actually favor (and have higher K cat values for) aldehyde reduction over alcohol oxidation, an observation made for most alcohol/aldehyde pairs (Mardh and Vallee, 1986;Hoog et al, 2001). There are five classes of human ADH enzymes (corresponding to at least seven individual human genes) that differ significantly in substrate specificities and inhibition characteristics (Hoog et al, 2001).…”

“…In DOPEGAL metabolism, hepatic class I ADH isozymes catalyze the conversion of MHPG to the aldehyde, MOPEGAL (Mardh et al, 1985), which is then converted by hepatic ALDH to VMA (Messiha, 1978). Liver class I ADH enzymes have also been reported to efficiently catalyze the reduction of DOPAL (K m ϭ 8.9 M), and it has been reported that class I ADH is involved in the metabolism of catecholamines (Mardh and Vallee, 1986;Svensson et al, 1999). The presence of ADH class 1 mRNA has been reported in adult rat brain (Martinez et al, 2001).…”

Hydroxytyrosol Disposition in Humans

“…It is not surprising, therefore, to find it in biological fluids, despite a strict washout in the dietary protocol. In fact, homovanillic acid, one of the main metabolites of dopamine, has also been reported as a major metabolite of Ht (30,31 ). These observations also raise questions concerning the extent HT from the diet and dihydroxyphenylethanol from dopamine metabolism may participate jointly as an antioxidant system in the body.…”

Tyrosol and hydroxytyrosol are absorbed from moderate and sustained doses of virgin olive oil in humans

“…Alternatively, dihidroxyphenylethanol has been identified as a metabolite from dopamine metabolism in dopaminergic cell lines (Lamensdorf et al, 2000). Other in vitro studies have demonstrated the formation of hydroxytyrosol as a result of 3,4-dihidroxyphenylacetaldehyde (DOPAL), a dopamine metabolite, reduction by the human liver alcohol dehydrogenase isoenzyme (Mardh & Vallee, 1986). Tyrosine derived from the breakdown of dietary protein could be a precursor of endogenous formation of dopamine in cells containing the tyrosine hydroxylase enzyme (Goldstein et al, 1999).…”