In vivo mammalian metabolism of methylamine and methylurea and their metabolic interrelationship
Dar, M.S.; Bowman, E.R.
Drug Metabolism and Disposition the Biological Fate of Chemicals 13(6): 682-689
1985
ISSN/ISBN: 0090-9556 PMID: 2867871 Document Number: 445
The metabolism of methylamine has been investigated in the rabbit and rat, and evidence has been presented to show that the metabolism of the compound leads to the formation and excretion of methylurea, a metabolite suspected, but never conclusively shown, to exist by previous investigators. Urinary methylurea, after the administration of methyl-14C-amine, was shown to have 14C activity at both the carbonyl and methyl portions (groups) of the molecule. 14C activity in the carbonyl group of methylurea was derived from the same metabolic CO2 pool that is used in the formation of urinary urea and respiratory carbon dioxide. Administration of methyl-14C-amine led to the formation of respiratory 14CO2, as noted by various investigators, and it was shown that during a 24-hr period the ratio of specific activity (urea/respiratory CO2) approached 1, in aggreement with previous data reported by MacKenzie and du Vigneaud [J. Biol. Chem. 172, 353-354 (1948)]. In order to quantitatively investigate some aspects of metabolism of methylurea, a procedure was developed for the convenient synthesis of N-methyl-14C-carbonylurea. In a series of experiments, the urinary urea of the animals injected with N-methyl-14C-carbonyl-urea and N-methyl-14C-urea was examined for radioactivity. Only limited amounts of 14C activity were found in the carbonyl group of urea following administration of N-methyl-14C-urea. However, after the administration of N-methyl-14C-carbonyl-urea, urinary area contained a 200-fold excess of 14C-carbonyl-urea. However, after the administration of N-methyl-14C-carbonyl-urea, urinary urea contained a 200-fold excess of 14C activity. These data indicate a metabolism of methylurea to urea which is accomplished in such a manner as to maintain the integrity of one or more of the nitrogen carbon bonds of methylurea. The data presently available do not permit exclusion of either route as a participating factor in the demethylation of methylurea and point to the necessity for additional studies for complete elucidation of the mechanisms.
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