Metabolism of d-glucuronolactone in mammalian systems. Identification of d-glucaric acid as a normal constituent of urine

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Abstract
Mammalian urine contained a dialysable heat-stable factor which after acid treatment was a specific competitive inhibitor for [beta]-glucuronidase; inhibition became maximal after urine treatment at pH 2 and 100[degree], but potentiation was significant at the pH and temperature of [beta]-glucuronidase assay. The inhibitor potentiation was reversed by alkali treatment and re-established by further acid treatment. Oral dosage of D-glucuronolactone to man, guinea pig and rat elevated greatly the excretion of the factor, whereas D-glucuronate or D-galacturonate administered to man had no appreciable effect on the excretion of the inhibitor or of uronic acid. D-Glucaric acid was isolated from human pregnancy urine, which contained larger quantities of the factor than normal women''s urine, and from human urine after dosage with D-glucuronolactone. It was identified as the bisphenylhydrazide derivative and by chromatographic examination. It was concluded that D-glucarate was responsible for the acid potentiation of the inhibition of [beta]-glucuronidase by normal urine, through partial conversion into the (1>4)-lactone, and that D-glucaric acid is a product of D-glucuronolactone metabolism in mammals. The significance of this work on the measurement of urinary [beta]-glucuronidase activity, and on the isolation from urine of furan-2,5-dicarboxylic acid, is discussed.