Stereochemistry and kinetic isotope effects in the bovine plasma amine oxidase catalyzed oxidation of dopamine

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Abstract
The stereochemistry of the bovine plasma amine oxidase catalyzed oxidation of 2-(3,4-dihydroxyphenyl)-ethylamine (dopamine) was investigated by comparing 3H/14C ratios of 3,4-dibenzyloxyphenethyl alcohols, derived from 3,4-dihydroxyphenylacetaldehydes, to starting dopamines chirally labeled at C-1 and C-2. The oxidation of [2RS-3H]-, [2R-3H]- and [2S-3H]dopamine leads to products which have retained 53, 59, and 47% of their 3H. Similarly, oxidation of [1RS-3H]-, [1R-3H]-, and [1S-3H]dopamine leads to an 80, 80, and 92% retention of 3H. The configurational purity of 3H at C-2 of dopamine and C-1 of the dopamine precursor 3-methoxy-4-hydroxyphenethylamine was confirmed employing dopamine-.beta.-hydroxylase (specific for the pro-R hydrogen at C-2) and pea seedling amine oxidase (specific for the pro-S hydrogen at C-1). Chromatographically resolved isozymes of bovine plasma amine oxidase lead to the same stereochemical result as pooled enzyme fractions. Carbon interchange and 3H transfer in the ethylamine side chain of dopamine was ruled out as the source of the apparent nonstereospecificity. Estimated primary tritium isotope effects are 1 for [2-3H]dopamines and 5-6 and 26-34 for [1R-3H]- and [1S-3H]dopamine, respectively. The presence of alternate dopamine binding modes, is apparently characterized and absolute but opposing stereochemistries and differential primary 3H isotope effects at C-1.