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Biomedical subjects

J C David

Publications and source records attributed to J C David.

87 records · Page 5Linked to original sources
PubMed1976

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.

Animals↗
PubMed1976

Evidence for the possible formation of a toxic tyrosine metabolite by the liver microsomal drug metabolizing system.

The toxicity of tyrosine in the mouse was found to be affected by agents which interact with the liver microsomal drug metabolizing system. Pretreatment of mice with SKF 525A or cobaltous chloride, two different types of inhibitors of the drug metabolizing system, afforded a marked protection against tyrosine toxicity. Pretreatment with phenobarbital or 3-methylcholanthrene, two inducers of the drug metabolizing system, potentiated the toxic effects of tyrosine. Toxicity, as determined by lethality, was also found to be correlated with a depletion of liver glutathione levels. It is concluded that the liver microsomal drug metabolizing system is capable of converting tyrosine to a toxic metabolite, conceivably a 2.3 epoxide of tyrosine. The present results are discussed in relation to the human disease tyrosinemia (tyrosinosis).

Animals↗
PubMed1974

Decarboxylation to tyramine: a major route of tyrosine metabolism in mammals.

Metabolism of tyrosine was examined in mice, some of which had been treated with an inhibitor of aromatic-L-amino-acid decarboxylase. The results of the study indicate that as the plasma and tissue levels of tyrosine are elevated, decarboxylation to tyramine becomes the predominant route of metabolism. At the highest dose of tyrosine used (1.5 g/kg), it was found that 42% of the administered dose was decarboxylated within 6 hr and only 11.5% was metabolized by the tyrosine aminotransferase pathway.

Animals↗