Studies in detoxication. 18. A study of the relation between conjugation and deamination of p-hydroxybenzylamine and related compounds in the rabbit

Abstract

The metabolic fates in the rabbit of p-hydroxybenzylamine, p-hydroxybenzylmethylamine, p-hydroxybenzylacetamide, p-hydroxy-benzaldehyde and p-hydroxybenzoic acid were compared. The main metabolic products of p-hydroxybenzylamine are free p-hydroxybenzoic acid (about 40%) and the glucuronide (39%) and ethereal sulfate (19%) of p-hydroxybenzoic acid. Small amts. of conjugated p-hydroxybenzaldehyde, p-hydroxyhippuric acid and conjugated protocatechuic acid aae. also excreted. ,p-Hydroxy-benzylmethylamine is also converted into p-hydroxybenzoic acid derivs., but in this case the glucuronide formed is 54% of the dose whereas the sulfate is 7%. p-Hydroxybenzylacetamide is not deacetylated in vivo and does not produce derivs. of p-hydroxybenzoic acid in the urine. It is mainly transformed (60%) into p-acetamidomethylphenylglucuronide which was isolated and characterized as its triacetyl methyl ester, p-Hydroxybenzylacetamide and its O-acetyl deriv. were prepared and described for the first time. p-Hydroxybenzaldehyde is largely converted into the glucuronide (33%) and sulfate (9%) of p-hydroxybenzoic acid, A small amt. (2-3%) is, however, excreted as p-glucurono-sidobenzaldehyde which was isolated as a 2,4-dinitrophenylhy-drazone. p-Hydroxybenzoic acid is the least conjugated of all the compounds studied and forms only 18% glucuronide and 9% ethe-r real sulfate. The results indicate that with phenolic amines of the type studied here the extent of glucuronic acid conjugation is inversely proportional to the rate of deamination, the conjugation being highest where no deamination takes place. The significance of this conclusion is discussed.