Tubular CO2 production from glutamine in the rat: segmental profile and modulation

The present study was designed to test whether tubular carbon dioxide production from the carbon skeleton of uniformly 14C-labelled glutamine exhibits quantitative and qualitative segmental heterogeneity. Our results show that CO2 production from glutamine in the proximal convoluted tubule (PCT) was dependent on substrate concentrations and is saturable at 10(-4) M of glutamine. Glutamine oxidation was demonstrable in all nephron segments examined. The PCT is the quantitatively predominant site of glutamine oxidation. Intermediate nephron segments, however, such as the thick ascending limb (MAL) and the distal convoluted tubule possess a significant capacity for glutamine oxidation, particularly when examined in terms of tubular protein content. Modulation of glutamine oxidation by extracellular pH was segment specific. Stimulation by acidosis and inhibition by alkalosis were observed in the PCT while carbon dioxide production from glutamine in the MAL was pH-insensitive. Glutamine oxidation was closely linked to sodium transport and greatly decreased by inhibition of Na-K-ATPase. In both the PCT and MAL, glutamine oxidation was inhibited by high extracellular potassium concentrations and in the PCT enhanced by extracellular hypokalemia. N-Ethyl maleiamide, an inhibitor of proton ATPase, led to almost complete cessation of CO2 production from the substrate in both PCT and MAL. Acetazolamide, an inhibitor of carbonic anhydrase, led to a partial reduction in carbon dioxide formation in the PCT, but did not affect glutamine oxidation in the MAL. We conclude that segmental qualitative heterogeneity characterizes oxidation of the carbon skeleton of glutamine with proximal segments showing the predictable effects of pH changes and carbonic anhydrase inhibition. The MAL appears to be nonmodulating.