The role of pH and the lack of a requirement for hydorgencarbonate in the regulation of hepatic glutamine metabolism.
The rate of net glutamine degradation in non-recirculating perfused rat liver was estimated by the release of urea, ammonia and alanine in steady states of operation of glutaminase. Corrected for a slight intracellular accumulation of glutamate, accounting for 7% of the flux at 5mM glutamine, the estimated glutaminase activity agrees well with measurements of glutamine removal described in the literature for recirculating perfusion experiments. Glutaminase activity was decreased when the perfusate pH was lowered (i) by infusion of hydrochloric acid, (ii) by increasing the CO2 concentration, or (iii) by decreasing the hydrogencarbonate concentration. Conversely, it was increased when the perfusate pH was increased by infusion of sodium hydroxide or by increasing the hydrogencarbonate concentration. However, glutaminase activity did not depend on medium hydrogencarbonate. When the hydrogencarbonate buffer system was replaced by DMO or by Hepes equilibrated with O2 (no CO2 present), there was practically no change in the observed rates. These results, obtained in an iso-pH system, are in contrast to recent suggestions of a role of hydrogencarbonate in the regulation of glutamine metabolism based on results from incubations of isolated mitochondria or hepatocytes. It is concluded that the conservation of glutamine by the inhibition of hepatic glutaminase, which provides glutamine for the pH regulation by renal glutaminase, can be increased not only in metabolic acidosis but also in respiratory acidosis associated with high hydrogencarbonate concentration.
D000409:Alanine / Q000096:biosynthesis; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism; D005972:Glutaminase / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D014508:Urea / Q000378:metabolism
D001639:Bicarbonates; D005971:Glutamates; D005973:Glutamine; D000641:Ammonia; D014508:Urea; D005972:Glutaminase; D000409:Alanine