PRODUCTION OF AMMONIA FROM HIPPURATE IN THE KIDNEY OF DIFFERENT SPECIES INCLUDING MAN - AN IN-VITRO STUDY WITH N-15-HIPPURATE

Hippurate, synthetized from benzoate and glycine in the liver and in t he kidney of several species modulates the activity of renal gamma-glu tamyl-transpeptidase. By this mechanism hippurate interferes with rena l intraluminal ammonia production. Besides, in the rat hippurate serve s as a minor substrate for renal ammoniagenesis as well. Hippurate may yield ammonia from its glycine moiety either after cleavage by hippur icase, or after condensation with an aldehyde according to Erlenmeyer' s reaction. This reaction results in producing equimolar amounts of am monia, benzoate and an alpha-keto acid, thus in a net gain of an acid equivalent. -In order to evaluate variability and extent of renal ammo nia production from hippurate in different species, experiments were c arried out on isolated tubular segments of the rat and on cortical kid ney slices of rat, cow, man and cat. The incubation medium was enriche d with 10mmol/l hippurate spiked with 5% of N-15-hippurate, some of th e known inhibitors of hippuricase and gamma GT as well as glyceraldehy de or propionaldehyde. Factors known to affect hippuricase or gamma GT did not interfere with renal ammonia production from hippurate, but g lyceraldehyde and propionaldehyde (up to 1mmol/l) had a stimulating ef fect. Renal ammoniagenesis from hippurate as well as production of ben zoate was lowest in the cow (similar to 0.1%), amounted to 1-2% in rat and man and reached high values in the cat (up to 15% of the total am monia production). These results indicate that hippurate could have ph ysiological significance in the renal metabolism of some species.