Lethality of tyrosine in mice: its potentiation by decarboxylase inhibitors and reversal byascorbic acid.
High doses of tyrosine were found to be lethal in mice. The lethality was potentiated by decarboxylase inhibitors which acted by elevating tissues tyrosine levels when given together with large amounts of tyrosine. The lethality of either tyrosine or tyrosine given in combination with decarboxylase inhibitors was found to be correlated with the elevation of tyrosine levels in liver. This toxicity does not appear to involve either tyramine or p-hydroxyphenylpyruvic acid formation. Ascorbic acid pretreatment afforded a marked protection against tyrosine toxicity. This compound was found to prevent the elevation of tissue tyrosine levels by stimulating p-hydroxyphenylpyruvic acid oxidase, increasing the urinary excretion and inhibiting the gastrointestinal absorption of tyrosine.
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001545:Benserazide; D001958:Brocresine / Q000494:pharmacology; D002230:Carbidopa / Q000494:pharmacology; D004357:Drug Synergism; D007408:Intestinal Absorption / Q000187:drug effects; D007668:Kidney / Q000201:enzymology; D007928:Lethal Dose 50; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D010667:Phenylpyruvic Acids / Q000378:metabolism; D014443:Tyrosine / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity*; D014445:Tyrosine Decarboxylase / Q000037:antagonists & inhibitors*
D010667:Phenylpyruvic Acids; D001958:Brocresine; D014443:Tyrosine; D001545:Benserazide; D014445:Tyrosine Decarboxylase; D002230:Carbidopa; D001205:Ascorbic Acid