Martha B. MacLeod

Metabolism of Glutamine by the Intact Functioning Kidney of the Dog STUDIES IN METABOLIC ACIDOSIS AND ALKALOSIS

The renal conversion of glutamine to glucose and its oxidation to CO(2) were compared in dogs in chronic metabolic acidosis and alkalosis. These studies were performed at normal endogenous levels of glutamine utilizing glutamine-(34)C (uniformly labeled) as a tracer. It was observed in five experiments in acidosis that mean renal extraction of glutamine by one kidney amounted to 27.7 mumoles/min. Of this quantity, 5.34 mumoles/min was converted to glucose, and 17.5 mumoles/min was oxidized to CO(2). Acidotic animals excreted an average of 41 mumoles/min of ammonia in the urine formed by one kidney. In contrast, in five experiments in alkalosis, mean renal extraction of glutamine amounted to 8.04 mumoles/min. Of this quantity, 0.92 mumole/min was converted to glucose, and 4.99 mumoles/min was oxidized to CO(2). Alkalotic animals excreted an average of 3.23 mumoles/min of ammonia in the urine. We conclude that renal gluconeogenesis is not rate limiting for the production and excretion of ammonia in either acidosis or alkalosis. Since 40% of total CO(2) production is derived from oxidation of glutamine by the acidotic kidney and 14% by the alkalotic kidney, it is apparent that renal energy sources change with acid-base state and that glutamine constitutes a major metabolic fuel in acidosis.

The renal response to chronic respiratory acidosis.

An increase in the carbon dioxide tension of the body fluids is accompanied by an increase in the concentration of bicarbonate bound base, a fact which minimizes the change in pH that would otherwise ensue (1, 2). A priori, it is evident that an elevated plasma bicarbonate concentration can be maintained only by enhancement of the rate of renal tubular reabsorption of bicarbonate. That such enhancement occurs in response to acute respiratory acidosis has been established by experiments performed in our laboratory as well as in other laboratories (3-5). It has also been shown that the elevated pCO2, and not the change in pH, is the stimulus responsible for enhancing this tubular activity.