Substrate interconversion in dog kidney cortex slices: regulation by ECF pH

The kidney utilizes far more substrate than it can oxidize. Some of the factors that regulate the metabolic fates of the excess substrate utilized by slices of dog kidney cortex were investigated. They were found to be: substrate specificity, substrate concentration, and the pH of extracellular fluid (ECF pH). Neutral substrates, glycerol or fructose, were converted largely to glucose and lactic acid and, to a smaller extent, to CO₂; as substrate concentration was raised, the relative amounts of glucose or lactic acid formed were regulated by ECF pH in such a manner as to suggest a pH regulatory feedback mechanism. More of two acidic substrates, lactate and α KG, were oxidized to CO₂, and their oxidation was not affected by changes in medium pH. In contrast, conversion of citrate to CO₂ and glucose increased as medium pH decreased. There appear to be two types of metabolic pathways in kidney cortex: a pathway for energy production by aerobic oxidation, utilizing primarily acidic substances; and a pathway for conversion of certain substrates, which are utilizable by few tissues, to products which are taken up by most tissues. This latter pathway is regulated by ECF pH and substrate concentration and, in turn, may regulate the substrate concentrations made available to other tissues.