title: Human liver enzymes responsible for metabolic elimination of tyramine; a vasopressor agent from daily food.
abstract: Dietary tyramine is associated with hypertensive crises because of its ability to induce the release of catecholamines. The roles of monoamine oxidase (MAO); flavin-containing monooxygenase (FMO); and cytochrome P450 2D6 (CYP2D6) were studied in terms of the enzymatic elimination of tyramine in vitro at a substrate concentration of 1.0 µM; which is relevant to in vivo serum concentrations. Tyramine elimination by human liver supernatant fractions was decreased by ˜70% in the absence of NADPH. Pargyline; an MAO inhibitor; decreased tyramine elimination rates by ˜30%. Among recombinant P450 and FMO enzymes; CYP2D6 had a high activity in terms of tyramine elimination. Tyramine elimination rates were inhibited by quinidine and significantly correlated with bufuralol 1'-hydroxylation activities (a CYP2D6 marker). Liver microsomes genotyped for CYP2D6*10/*10 and CYP2D6*4/*4 showed low and undetectable activities; respectively; compared with the wild-type CYP2D6*1/*1. The present results suggest that tyramine is eliminated mainly by polymorphic CYP2D6. Tyramine toxicity resulting from differences in individual metabolic elimination is thus genetically determined.
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Niwa
authors.forename: Norie
authors.initials: N
authors.lastname: Murayama
authors.forename: Hiromi
authors.initials: H
authors.lastname: Umeyama
authors.forename: Makiko
authors.initials: M
authors.lastname: Shimizu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamazaki
mesh_terms: D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism; D009249:NADP / Q000378:metabolism*; D010105:Oxygenases / Q000378:metabolism; D011110:Polymorphism, Genetic; D014439:Tyramine / Q000493:pharmacokinetics*; D014662:Vasoconstrictor Agents / Q000493:pharmacokinetics
chemical_list: D014662:Vasoconstrictor Agents; D009249:NADP; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); D019389:Cytochrome P-450 CYP2D6; D008995:Monoamine Oxidase; D014439:Tyramine