Sites of enzyme activity along the nephron

Renal tubular functions can be characterized as energy-consuming transport processes which are driven by metabolic energy-yielding reactions. In this context it has been argued that sodium transport is the major work function in mammalian kidney. Ullrich, Rumrich and Klöss have shown recently that in the absence of intraluminal sodium the transport of amino acids and hexoses approaches zero [1, 2]. Frömter, Rumrich and Ullrich have calculated that one-third of the net transepithelial sodium flux is transported actively [3]. At least 80% of this active transport depends on adenosine triphosphate (ATP) [4]. Thus, knowledge of the intrarenal localization of metabolic pathways providing ATP would give more insight into the linkage between metabolism and transport processes.Fatty acids, ketone bodies, intermediates of the citric acid cycle, amino acids, lactate and glycerol are known to contribute to the energy supply of the kidney of various mammals including man (for review see [5]). However, the physiological significance of the measured uptake rates of these substrates for renal function is only partially known at present.Metabolism of renal cortex is characterized by fatty acid oxidation and gluconeogenesis [6]. In contrast, renal medulla reveals a rapid rate of aerobic and anaerobic glucose metabolism and probably depends on glucose as a respiratory fuel [7,8]. However, it is not clear whether glucose metabolism provides significant amounts of energy in the whole kidney. Some authors state that glucose oxidation may be neglected whereas others have found that glucose supplied up to 30% of the respiratory fuel [5, 9]. These conflicting results may be explained by the different methods: Almost all measurements of metabolic fluxes were made with the whole organ or in tissue slices of the various zones—i.e., cortex, outer and inner medulla. Since each zone is a mixture of different cell types, no information about the metabolic pattern along the nephron is available from these studies. This led us to investigate renal metabolism in well-defined structures of the nephron.The purpose of this review is to summarize some results obtained by the determination of enzymes of carbohydrate and energy metabolism in single portions of the rat nephron, and to discuss their possible relationships to renal transport processes. It should be kept in mind, however, that the data obtained with these methods can be interpreted only with some limitations. Enzyme activities measured in vitro cannot be compared with metabolic fluxes through the respective pathway in vivo, since regulatory mechanism-like substrate and cofactor concentrations, allosteric regulation and other microenvironmental factors are not considered. The measured activities can, however, be used to calculate roughly the maximal metabolic capacities of the respective step. Moreover, it has been shown repeatedly that the typical pattern of enzymes in various tissues correlates with metabolic capacities of that tissue [10, 11]. Enzymes which catalyze irreversible steps are best suited to characterize the distribution of glycolysis, pentose phosphate pathway, gluconeogenesis and citric acid cycle activity (Fig. 1). For comparison, bidirectional enzymes which serve to catalyze more than one metabolic pathway were also included