Kinetic studies of the metabolism of foreign organic compounds. 7. Toluic acids and N-tolylureas

Abstract

Part 6 Biochem. J. 1955, 59, 162. The determination of ureido compounds by the color reaction with tryptophan and diacetylmonoxime is described. N-(4 hydroxy-2-methylphenyl) urea and N-(4-hydroxy-3-methyl phenyl) urea are conjugated with sufluric and glucuronic acids in the rabbit, with about 40% of the dose excreted unchanged. At 0.5 g/kg, the excretion curves of the conjugates were exponential, suggesting a system of 2 simultaneous conjugation reactions with first order kinetics. The o-tolylurea is hydroxylated only so that the first-order velocity constant for nuclear hydroxylation, kb.0H, can be evaluated; p-tolylurea is not hydroxylated, oxidation of the methyl group occurring, giving values for kb-COOH; m-tolylurea undergoes both hydroxylation and oxidation, so both kb.oh, and kb-OOOH can be evaluated. Similar constants were calculated for the conjugation of the toluic acids with glycine. The absorption of ureido phenols and ureidobenzoic acid is complete in 3 hours while that of the tolylureas is relatively slow. Values are given for the appropriate velocity constants.