Primary route of metabolism of norepinephrine and epinephrine. COMT, catechol-O-methyltransferase; MAO, monoamine oxidase.

Although either COMT or MAO may act first on circulating norepinephrine or epinephrine, COMT is the more rapidly acting enzyme, and therefore more molecules are O-methylated and then deaminated than the reverse. Some norepinephrine and epinephrine appear unchanged in the urine. The larger portion, however, is metabolized and the products of metabolism excreted in the urine, often as conjugates.

Measurements of norepinephrine, epinephrine, and their metabolites in the urine constitute valuable diagnostic aids, particularly in the detection of tumors that synthesize and secrete norepinephrine and epinephrine (e.g., pheochromocytoma).

Catecholamines can be transported into effector cells (extraneuronal uptake). These cells generally contain both COMT and MAO. The combined processes of extraneuronal uptake and O-methylation are believed to be a minor but functionally significant, site of irreversible loss of catecholamines. The precise role of extraneuronal MAO in transmitter inactivation remains unknown.

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