Metabolism of 2-phenylethylamine to phenylacetic acid, via the intermediate phenylacetaldehyde, by freshly prepared and cryopreserved guinea pig liver slices.
BACKGROUND
2-Phenylethylamine is an endogenous amine, which acts as a neuromodulator of dopaminergic responses. Exogenous 2-phenylethylamine is found in certain foodstuffs and may cause toxic side-effects in susceptible individuals.


METHODS
The present investigation examined the metabolism of 2-phenylethylamine to phenylacetic acid, via phenylacetaldehyde, in freshly prepared and cryopreserved liver slices. Additionally, it compared the relative contribution of aldehyde oxidase, xanthine oxidase and aldehyde dehydrogenase by using specific inhibitors for each oxidizing enzyme.


RESULTS
In freshly prepared and cryopreserved liver slices, phenylacetic acid was the main metabolite of 2-phenylethalamine. In freshly prepared liver slices, phenylacetic acid was completely inhibited by disulfiram (inhibitor of aldehyde dehydrogenase), whereas isovanillin (inhibitor of aldehyde oxidase) inhibited acid formation to a lesser extent and allopurinol (inhibitor of xanthine oxidase) had no effect. In cryopreserved liver slices, isovanillin inhibited phenylacetic acid by 85%, whereas disulfiram inhibited acid formation to a lesser extent and allopurinol had no effect.


CONCLUSIONS
In liver slices, 2-phenylethylamine is rapidly oxidized to phenylacetic acid, via phenylacetaldehyde, by aldehyde dehydrogenase and aldehyde oxidase with no contribution from xanthine oxidase.
Panoutsopoulos
Georgios I
GI
Department of Experimental Pharmacology, Medical School, Athens University, 75 Mikras Asias St., Athens 115 27, Greece. geopanou@otenet.gr
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D042931:Aldehyde Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001547:Benzaldehydes / Q000494:pharmacology; D015925:Cryopreservation; D004221:Disulfiram / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010627:Phenethylamines / Q000378:metabolism*; D010648:Phenylacetates / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism
D001547:Benzaldehydes; D004791:Enzyme Inhibitors; D010627:Phenethylamines; D010648:Phenylacetates; C029261:phenethylamine; C093382:isovanillin; D000493:Allopurinol; D014969:Xanthine Oxidase; D000444:Aldehyde Dehydrogenase; D042931:Aldehyde Oxidase; C025136:phenylacetic acid; D000079:Acetaldehyde; D004221:Disulfiram; C013192:phenylacetaldehyde