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Monoamine oxidase and catecholamine metabolism
1National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
Journal of Neural Transmission. Supplementum
|January 1, 1994
Summary
Monoamine oxidase (MAO) metabolizes catecholamines, with its role clarified by MAO inhibitors and studies on urinary metabolites like VMA and HVA. Research explored two pathways for norepinephrine metabolism, investigating the roles of MAO and COMT.
Area of Science:
- Biochemistry
- Pharmacology
- Enzymology
Background:
- Monoamine oxidase (MAO) was initially identified as tyramine oxidase over 60 years ago.
- MAO's substrates were later expanded to include key catecholamines like epinephrine, norepinephrine, and dopamine.
- Early research distinguished MAO from other amine oxidases, such as diamine oxidase.
Purpose of the Study:
- To establish the role of MAO in catecholamine metabolism.
- To elucidate the metabolic pathways of norepinephrine, specifically the interplay between deamination and O-methylation.
- To investigate the physiological significance of MAO and catechol-O-methyl transferase (COMT) in catecholamine action termination.
Main Methods:
- Utilized isotopically labeled epinephrine and MAO inhibitors (e.g., iproniazid) to track metabolic fate.
- Employed paper chromatography to separate and identify urinary metabolites of norepinephrine.
- Applied biochemical and physiological methods, including drug-induced alterations in catecholamine metabolism, to assess pathway importance.
Main Results:
- Demonstrated that MAO is responsible for metabolizing approximately half of administered catecholamines.
- Identified major urinary metabolites of norepinephrine as vanillyl mandelic acid (VMA) and homovanillic acid (HVA).
- Revealed two potential metabolic routes for norepinephrine: deamination followed by O-methylation, or O-methylation followed by deamination.
Conclusions:
- Confirmed MAO's critical role in catecholamine metabolism.
- Highlighted the discovery of catechol-O-methyl transferase (COMT) as a key enzyme in a parallel metabolic pathway.
- Established the foundation for understanding how MAO and COMT collectively regulate catecholamine levels and physiological actions.