AJP - Renal Physiology, Vol 249, Issue 4 573-F581, Copyright © 1985 by American Physiological Society
Effect of bicarbonate on glutamine and glutamate metabolism by rat kidney cortex mitochondria
R. C. Scaduto Jr and A. C. Schoolwerth
Isolated rat kidney cortex mitochondria were incubated at pH 7.4 in the
presence or absence of a CO2/bicarbonate buffer (28 mM) to investigate the
pH-independent role of bicarbonate on glutamine and glutamate metabolism.
Changes in the concentration of key intermediates and products during the
incubations were used to calculate metabolite flux rates through specific
mitochondrial enzymes. With 1 mM glutamine and 2 mM glutamate as
substrates, bicarbonate caused an inhibition of glutamate oxalacetate
transaminase flux and a stimulation of glutamate deamination. The same
effects were also produced with addition of either aminooxyacetate or
malonate. These effects of bicarbonate were prevented when 0.2 mM malate
was included as an additional substrate. Bicarbonate ion was identified as
a potent competitive inhibitor of rat kidney cortex succinate
dehydrogenase. These results indicate that aminooxyacetate, malonate, and
bicarbonate all act to stimulate glutamate deamination through a
suppression of glutamate transamination, and that the control by
transamination of glutamate deamination is due to alterations in
alpha-ketoglutarate metabolism. In contrast, in mitochondria incubated with
glutamine in the absence of glutamate, bicarbonate was found to inhibit
glutamate dehydrogenase flux. This effect was found to be due in part to
the lower intramitochondrial pH observed in incubations with bicarbonate.
These findings indicate that bicarbonate ion, independent of pH, may have
an important regulatory role in renal glutamine and glutamate metabolism.
