Hippurate is known to be synthesized from benzoate and glycine in the
liver and kidney. It takes part in renal ammoniagenesis by modulating
the activity of gamma-glutamyl transpeptidase (gamma GT). Due to its c
hemical structure, however, hippurate might also serve as a substrate
of renal ammoniagenesis. Hippurate may yield ammonia either having bee
n cleaved by hippuricase or by Erlenmeyer's reaction after condensatio
n with an aldehyde. In order to elucidate the possibility of hippurate
being a substrate of renal ammoniagenesis, experiments were carried o
ut on cortical kidney slices and on isolated tubular segments of the r
at. The incubation medium (pH 7.1) was enriched with 10 mmol/l hippura
te spiked with N-15-hippurate, some of the known competitive inhibitor
s of hippuricase, acivicin and different aldehydes. Factors known to a
ffect hippuricase or gamma GT did not interfere with renal ammonia pro
duction. Glyceraldehyde (up to 1.0 mmol/l) but not glycerate had a sti
mulating effect, especially on the ammoniagenesis from hippurate. In n
ormal rats fed a vegetarian diet, 1% of the added N-15 moiety was foun
d to be (NH3)-N-15. Renal (NH3)-N-15 production was significantly grea
ter if, prior to the experiments, the animals were either acidotic or
had a reduced renal mass or were fed animal proteins. These results in
dicate that hippurate may, to a certain extent, serve as substrate for
ammoniagenesis.