Energy turnover and the production of ammonium by the kidney: effect of hypernatremia

Abstract

HALPERIN, M. L., and CHEN, C.-B. 1992. Energy turnover and the production of ammonium by the kidney: effect of hypernatremia. Can. J. Physiol. Pharmacol. 70: 8 -12.The pupsse of this study was to explore further the relation between the rates of oxygen consumption and ammonium (NH,+) production in the kidney during chronic metabolic acidosis. The experimental model was the dog with chronic metabolic acidosis because of the extensive background literature in this species. Chronic metabolic acidosis was produced by h e ingestion of 10 mmol NH,CI/kg body weight for 5 days. There was a significant increase in the rate of oxygen extraction when hyprnatremia was present. Despite this rise in the rate of oxygen consumption, there was no increase in the rate of NH4+ production nor in the rate of glutamine extraction. These data suggest that hyprnatremia might prevent a further augmentation in glutamine extraction when the rate of oxygen consumption rises. In addition, a larger proportion of the NM,+ produced was excreted in the urine during hypernatremia. This increase was associated with a rise in the urine flow rate, but not with a fall in urine pH.Key words: Acid -base, ATP, glutamine, energy metabolism, metabolic acidosis, metabolic regulation, nee acid excretion, oxygen consumption. During chronic metabolic acidosis, the expected renal response is to generate new bicarbonate; this is accomplished rnahly by the production and excretion of TWO major steps are involved: first, glutamine is metabolized in cells of the proximal tubule, yielding NH4+ and bicarbonate as products (Halperin et al. 1991); second, the cation, NH4+, must be transferred to the urine (Knepper et d. 1989)* During the metabolism sf glutamiwe to either glucose or C 0 2 , ATP is produced (Hdperiw et al. 1982). Hence the rate of turnover of energy (ATP) could limit the synthesis of N h f in these cells because no organ or organelle can synthesize ATP at a rate that exceeds its rate of utilization even for 1 min, owing to the very small quantity of ADP in cells (Hllatt 1972; Hdperin et al. 1985b; Hdperin et al. 1982; Jungas et d. 1992). Since at least 90% sf the ATP turnover in the kidney appears to be related to sodium reabsorption (Mandel and Balaban 198 I), owe might anticipate that a direct relationship exists between the rates of oxygen consumption and gllutarnine oxidation (Halperin et daB. 1985). Two exceptions to this rule have been observed in dogs with chronic metabolic acidosis. 1976)) were infbased and oxidized, ATP was produced without the synthesis sf NH4+. Now there was a substantial (and pre-'Author for correspondence.Printcd rn Canada i Imprime au Canada dictable) decline in the rate of NH4+ pr~duction. Second, during acute hyponatremia, the rate of oxygen consumption rose, but no extra glgltamine was extracted. In this setting, there was complete oxidation and ns transamination of glutamine (Hdprin md Chen 1990), presumably reflecting increased oxidation s f alanine.To explore the relationship between the consumption of oxygen and ...