The kinetics of lactate and pyruvate (1 and 5 mM in each case) metabolism was studied in isolated dog renal tubules. Utilization of these two substrates and the production of glucose, pyruvate, or lactate, and alanine were determined. The rates of lactate and pyruvate utilization and of glucose production were constant during 60 min of incubation. Glucose production from pyruvate was less than that from lactate. Addition of albumin to the incubation medium greatly inhibited lactate and pyruvate utilization at both substrate concentrations. It stimulated, however, glucose production from 1 mM, but not 5 mM, lactate or pyruvate. These effects were found to be due to the presence of fatty acids in the albumin solution used. In the absence of fatty acids, glucose production represented 35 to 40% of lactate uptake, but represented less than 20% of pyruvate uptake. Fatty acids markedly enhanced the percentage of transformation of lactate and pyruvate into glucose, and that of pyruvate into lactate. Alanine represented 20% or less of lactate and pyruvate uptake. These results suggest that fatty acids have a regulatory influence on lactate and pyruvate dog kidney metabolism.

125Iodinated human beta 2 microglobulin (beta 2m, 5 to 30 mg) was administered to anesthetized rats. Clearance studies showed a low threshold of excretion of injected beta 2m and a high Tm of 400 to 600 micrograms X min-1 X kg-1. A glomerular sieving coefficient of 0.97 was calculated as the slope of the curve: beta 2m excretion rate = F (plasma beta 2m X glomerular filtration rate) for values above saturation. Electrophoresis analysis of proteinuria in agarose gel and sodium dodecyl sulfate polyacrylamide gel showed that injection of saturating doses of beta 2m induced the excretion of proteins of similar size but different charge and that of other proteins of different size. Among the latter, some were excreted transiently in association with beta 2m, whereas others had a delayed excretion suggesting existence of a complex mechanism of reabsorption whose steps remain to be elucidated.

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1. The pathways and the fate of glutamate carbon and nitrogen were investigated in isolated guinea-pig kidney-cortex tubules. 2. At low glutamate concentration (1 mM), the glutamate carbon skeleton was either completely oxidized or converted into glutamine. At high glutamate concentration (5 mM), glucose, lactate and alanine were additional products of glutamate metabolism. 3. At neither concentration of glutamate was there accumulation of ammonia. 4. Nitrogen-balance calculations and the release of 14CO2 from L-[ 1-_4C]glutamate (which gives an estimation of the flux of glutamate carbon skeleton through a-oxoglutarate dehydrogenase) clearly indicated that, despite the absence of ammonia accumulation, glutamate metabolism was initiated by the action of glutamate dehydrogenase and not by transamination reactions as suggested by Klahr, Schoolwerth & Bourgoignie [(1972) Am. J. Physiol. 222,[813][814][815][816][817][818][819][820] and Preuss [(1972) Am. J. Physiol. 222, 1395-13971. Additional evidence for this was obtained by the use of (i) amino-oxyacetate, an inhibitor of transaminases, which did not decrease glutamate removal, or (ii) L-methionine DL-sulphoximine, an inhibitor of glutamine synthetase, which caused an accumulation of ammonia from glutamate. 5. Addition of NH4Cl plus glutamate caused an increase in both glutamate removal and glutamine synthesis, demonstrating that the supply of ammonia via glutamate dehydrogenase is the rate-limiting step in glutamine formation from glutamate. NH4Cl also inhibited the flux of glutamate through glutamate dehydrogenase and the formation of glucose, alanine and lactate. 6. The activities of enzymes possibly involved in the glutamate conversion into pyruvate were measured in guinea-pig renal cortex. 7. Renal arteriovenousdifference measurements revealed that in vivo the guinea-pig kidney adds glutamine and alanine to the circulating blood.Since the initial work of Krebs (1935), it is known that, in contrast with kidney-cortex slices of dog, cat, pig, rat, sheep and pigeon, slices of guinea pig and rabbit do not release ammonia when incubated with glutamate. Krebs concluded that this was so in both the latter species because the ammonia formed by the deamination of glutamate via glutamate dehydrogenase was used for glutamine synthesis (see Krebs, 1935). However, the role of glutamate dehydrogenase in the metabolism of glutamate by guinea-pig and rabbit kidney slices has been questioned by and Preuss (1972), because these authors observed that glucose was formed from glutamate without concomitant accumulation of Vol. 188 ammonia; they concluded that the initial step in glutamate metabolism was transamination rather than oxidative deamination. So the pathways of renal metabolism of glutamate in these species remain uncertain.In an attempt to clarify this subject, we studied glutamate metabolism in isolated guinea-pig kidney tubules. The data obtained support the view of Krebs (1935) that glutamate dehydrogenase plays a central role in the renal metabolism of glutamat...

1 The pharmacological actions of piretanide, a new high efficiency diuretic, were studied in sixteen patients with GFR (inulin clearance) varying from 0.1 -2.5 ml/s. 2 After hydration and following two control periods, a single dose of 6 mg piretanide was ingested. Thereafter, urine was collected every 30 min for 2 h and every hour for the next 4 h. Fluid losses were replaced. 3 The following measurements were made: urine flow rate, clearances of inulin, PAH, urea, creatinine, uric acid, osmolar and free water clearances, excretion rates of sodium, chloride, potassium, calcium, phosphate, bicarbonate, ammonium, titratable acidity and urine pH. 4 Main results showed piretanide was efficient in the group with normal GFR (inulin clearance > 1.5 ml/s) and in the group with slightly decreased GFR (1.0 < inulin clearance < 1.4 ml/s), in terms of diuresis, natriuresis, kaliuresis and calciuresis. It was inefficient in the group with severe renal insufficiency (inulin clearance < 0.3 ml/s). 5Free water clearance showed preservation of diluting ability to a large extent. 6 In the three groups, no significant change in inulin clearance and PAH clearance occurred.