Metabolic aspects of acid-base change.

The state of metabolic acidosis involves changes of a varied and subtle nature in other organs as well as in the kidney. This fact has been illustrated in metabolic studies with glutamine, a major substrate of the kidney and of various other organs. In addition to the well-described increase in renal glutaminase enzymes, the hexose monophosphate-shunt enzymes also are much more active during metabolic acidosis; this phenomenon is limited to the kidney; its exact meaning remains speculative, but its possible relation to renal excretion of acid, lipogenesis, and gluconeogenesis during acidosis has been discussed. In the kidney there are metabolic changes associated with ammonium chloride acidosis that affect the basic mechanisms of gene-directed growth. There is a renal regenerative process during this kind of acidosis that resembles in some respects the compensatory hypertrophy in the remaining kidney after unilateral nephrectomy, from which it also differs in important ways. Lastly, we must now regard the role of glutamine in renal metabolism as an affair that goes well beyond the specific needs of formation of ammonia during the normal and acidotic states. Glutamine enters the general metabolic mill of the kidney, its carbon skeleton is incorporated into all the major tissue components, and it is an important source material for gluconeogenesis in the kidney; all of these renal functions of glutamine are increased during metabolic acidosis. Thus there is a fruitful field of exploration ahead, not only in the biochemical aspects of the renal response, but also in the metabolic interrelations among different organs during various types of acid-base change. This article, in concentrating on metabolic acidosis, gives only a glimpse of a broader picture to come.