AJP - Endocrinology and Metabolism, Vol 263, Issue 3 E493-E499, Copyright © 1992 by American Physiological Society
On the mechanism of stimulation of ureagenesis by gluconeogenic substrates: role of pyruvate carboxylase
A. Martin-Requero, G. Cipres, A. Rodriguez, M. S. Ayuso and R. Parrilla
Endocrine Physiology Unit, Centro de Investigaciones Biologicas, Madrid, Spain.
Gluconeogenic substrates, lactate or pyruvate, or ornithine produced 100%
increase of urea synthesis from NH4Cl. The combined administration of
ornithine and lactate (or pyruvate) produced more than additive effects,
indicating that they acted at different steps in a potentiating manner. The
uptake of ornithine was enhanced by gluconeogenic substrates. This finding
may explain, at least in part, the stimulating effect of these substrates
on ureagenesis from NH4Cl and ornithine. The gluconeogenic
substrate-induced stimulation of ureagenesis from NH4Cl was still observed
under conditions of reduced flux through pyruvate carboxylase, ruling out
that their action was exclusively mediated by the anaplerotic effect of
this enzyme. Pyruvate was a more potent stimulator of ureagenesis than
lactate and its effect less sensitive to pyruvate carboxylase inhibition.
These observations indicate that a correlation exists between stimulation
of ureagenesis by gluconeogenic substrates and flux through pyruvate
dehydrogenase. It is concluded that gluconeogenic substrates may stimulate
ureagenesis from NH4Cl by 1) increasing intracellular ornithine
availability and/or 2) enhancing flux through pyruvate dehydrogenase and
consequently the tricarboxylic acid cycle activity.
