Succinate Oxidation and Krebs Cycle as an Energy Source for Renal Tubular Transport Mechanisms

Abstract

Four chemically dissimilar compounds (maIonic acid, dehydroacetic acid, cincophen, chlorguanide) have been examined for their potency as succinoxidase inhibitors and their ability to suppress the renal tubular mechanism involved in the secretion of p-aminohippuric acid (PAH) and phenol-sulfonphthalein (PSP). The latter has been studied both in vivo in the dog and in vitro in the rabbit or guinea pig kidney slice. A close correlation has been shown to exist between the concns. of these compounds required to produce significant inhibition of succinoxidase activity in vitro, inhibition of PAH or PSP concn. by kidney slices in vitro, and doses necessary to suppress significantly renal tubular secretion of PAH (or PSP) in vivo. One of the 4 compounds, dehydroacetic acid, has been demonstrated to inhibit markedly a 2d secretory mechanism which exists in the renal tubules, namely the one involved in the secretion of N1-methylnicotinamide. In contrast to the above findings, malonic acid, dehydroacetic acid and cincophen, in doses which markedly suppress tubular secretion, have no significant effect on the reabsorptive capacities of the tubules for glucose and phosphate. On the basis of these results a schema of some of some of the energy sources for renal tubular transport mechanisms has been suggested. In this schema energy from succinate oxidation (and Krebs cycle oxidations) has been assigned a relative specificity in that it is more directly involved in tubular secretory processes than it is in the mechanisms employed for the absorption of glucose and phosphate.