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Pharmacological Reviews, Vol 11, 402-408, Copyright © 1959 by the American Society for Pharmacology and Experimental Therapeutics

THE METABOLISM OF CATECHOLAMINES IN VIVO AND IN VITRO

Julius Axelrod 1

1 Section on Pharmacology, Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland

The principal pathway for the metabolism of epinephrine in rat and man is O-methylation to metanephrine, a physiologically inactive metabolite, which is then conjugated or deaminated and oxidized to 3-methoxy-4-hydroxymandelic acid. Norepinephrine undergoes the same transformation in the rat and presumably in man.

An enzyme, catechol O-methyl transferase, that catalyzes the O-methylation of epinephrine, norepinephrine and other normally occurring and synthetic catechols, is described. Catechol-O-methyl transferase is widely distributed in all organ tissues including the autonomic and central nervous system, and appears to be the enzyme mainly responsible for the metabolism of epinephrine and norepinephrine.

Evidence is presented which indicates that amine oxidase is concerned chiefly with the deamination of the O-methylated metabolites of the catecholamines.

Enzymes involved in the conjugation of metanephrine and normetanephrine with glucuronic acid and the conversion of metanephrine to epinephrine are briefly described.

Metanephrine and normetanephrine were found to be normal constituents in rat urine and certain tissues of the rat.






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