Metabolism of homovanillamine to homovanillic acid in guinea pig liver slices.
OBJECTIVE
Homovanillamine is a biogenic amine that it is catalyzed to homovanillyl aldehyde by monoamine oxidase A and B, but the oxidation of its aldehyde to the acid derivative is usually ascribed to aldehyde dehydrogenase and a potential contribution of aldehyde oxidase and xanthine oxidase is usually ignored.


METHODS
The present investigation examines the metabolism of homovanillamine to its acid derivative by concurrent incubation with monoamine oxidase and aldehyde oxidase. In addition, the metabolism of homovanillamine in freshly prepared and cryopreserved liver slices is examined and the relative contribution of aldehyde oxidase, xanthine oxidase and aldehyde dehydrogenase activity by using specific inhibitors of each oxidizing enzyme is compared.


RESULTS
Homovanillamine was rapidly converted mainly to homovanillic acid when incubated with both momoamine oxidase and aldehyde oxidase. Homovanillic acid was also the main metabolite in the incubations of homovanillamine with freshly prepared or cryopreserved liver slices, via the intermediate homovanillyl aldehyde. The acid formation was 70-75 % inhibited by disulfiram (specific inhibitor of aldehyde dehydrogenase), whereas isovanillin (specific inhibitor of aldehyde oxidase) inhibited acid formation to a lesser extent (50-55 %) and allopurinol (specific inhibitor of xanthine oxidase) had almost no effect.


CONCLUSIONS
Homovanillamine is rapidly oxidized to its acid, via homovanillyl aldehyde, by aldehyde dehydrogenase and aldehyde oxidase with little or no contribution from xanthine oxidase.
Panoutsopoulos
Georgios
G
Department of Experimental Pharmacology, Medical School, Athens University, Greece. geopanou@otenet.gr
D042931:Aldehyde Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001547:Benzaldehydes / Q000494:pharmacology; D001679:Biogenic Amines / Q000378:metabolism*; D015925:Cryopreservation; D004221:Disulfiram / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006719:Homovanillic Acid / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008995:Monoamine Oxidase / Q000378:metabolism*
D001547:Benzaldehydes; D001679:Biogenic Amines; D004791:Enzyme Inhibitors; C503848:homovanillamine; C093382:isovanillin; D042931:Aldehyde Oxidase; D008995:Monoamine Oxidase; D004221:Disulfiram; D006719:Homovanillic Acid