[2-14C]Urate uptake was studied in brush border and basolateral membrane vesicles of rat renal cortex. In the absence of copper, urate equilibrated without metabolism of transported urate. Exposure of the vesicles to copper significantly stimulated uptake, and in these vesicles uptake was also stimulated by NaCl or KCl gradients. Allantoin accumulated in these vesicles due to oxidation of transported urate. This oxidation is ascribed to a copper-stimulated, membrane-associated uricase since purified uricase and the membranes had similar Km values, both were inhibited by oxonic acid, and extramembranal uricase was not detected. Oxonic acid and pyrazinoic acid inhibited both uptake and enzyme activity. These findings suggest that urate uptake is carrier mediated and that uricase may play some role in transport. In addition, it appears that a significant loss of copper occurs during isolation of membrane vesicles that profoundly affects the characteristics of urate uptake. Those properties of the membrane that influence urate uptake, however, can be restored by exposure of the membranes to copper.

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The energy cost of renal function in the intact kidney of the dog was assessed at a series of arterial perfusion pressures. Pressure was varied by partially inflating a balloon at the tip of a catheter positioned in the aorta above the origins of the renal arteries. Either L{ U-'4C]glutamine or L-U-14C] lactate was infused intravenously in tracer amounts throughout each experiment. Total renal CO2 production and 14C02 production from each isotope permitted assessment of total renal oxidative metabolism and the proportions derived from the two major substrates of the kidney. Stepwise inflation of the aortic balloon progressively lowered glomerular filtration rate, renal blood inflow, filtered and consequently reabsorbed Na+, total renal CO2 production, and 14CO2 derived from glutamine and lactate. The percent of total CO2 derived from lactate decreased more or less in proportion to the decrease in percent of total CO2 produced. Results were consistent with the view that reabsorption of sodium is the major energy sink of the kidney. They suggest that the oxidation of glutamine supplies energy for tubular transport and basal demands such as synthesis of hormones and maintenance of structure, whereas the oxidation of lactate supplies energy mainly for transport activities. The oxidative metabolism of the kidneys differs from that of other organs in at least two respects. First, the kidneys extract much less oxygen from each 100 ml of arterial blood than other organs do: on average, 1.5 ml in comparison with 4-15 ml (1). Second, the extraction of oxygen remains relatively constant at 1.5 ml/100 ml even though flow is reduced to as little as one-third of normal (2). The first difference does not mean that the energy cost of renal function is small. Blood flow and oxygen consumption are both large. The kidneys, which together constitute 0.5% of body weight, consume 5-8% of the oxygen consumed by the entire body at rest (1). Renal blood flow averages 20-25% of cardiac output at rest (1). The second difference derives from the fact that at normal perfusion pressures, the kidneys filter large volumes of plasma through their glomeruli and then face the energy-demanding task of actively reabsorbing the bulk of the components of the filtrate (3-9). In contrast, low perfusion pressure is commonly associated with low filtration rate and low rate of energy expenditure for reabsorption.Most renal physiologists believe that the major energy cost of renal function is related to the cost of reabsorbing sodium. It has been estimated that 20 to 30 sodium ions are reabsorbed for each molecule of oxygen consumed (3-9). Thus, in man, approximately 28,000 meq of sodium, contained in the 200 liters of plasma filtered each day, are reabsorbed at an energy cost equivalent to the consumption of 1200 mmol of oxygen (1). Energy must also be expended in biosynthesis of hormones and in maintenance of cellular structure.The experiments described in this paper were designed to measure the utilization of glutamine and lactate as fuels of do...

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