Carbohydrate metabolism in the isolated perfused rat kidney

Abstract

1. Anaerobic formation of lactate from glucose by isolated perfused rat kidney (411mumol/h per g dry wt.) was three times as fast as in aerobic conditions (138mumol/h per g). 2. In aerobic or in anaerobic conditions, the ratio of lactate production to glucose utilization was about 2. 3. Starvation or acidosis caused a decline of about 30% in the rate of aerobic glycolysis. 4. The rate of formation of glucose from lactate by perfused kidney from a well-fed rat, in the presence of 5mm-acetoacetate (83mumol/h per g dry wt.), was of the same order as the rate of aerobic glycolysis. 5. During perfusion with physiological concentrations of glucose (5mm) and lactate (2mm) there were negligible changes in the concentration of either substrate. 6. Comparison of kidneys perfused with lactate, from well-fed or starved rats, showed no major differences in contents of intermediates of gluconeogenesis. 7. The tissue concentrations of hexose monophosphates and C(3) phosphorylated glycolytic intermediates (except triose phosphate) were decreased in anaerobic conditions. 8. Aerobic metabolism of fructose by perfused kidney was rapid: the rate of glucose formation was 726mumol/h per g dry wt. and of lactate formation 168mumol/h per g (dry wt.). Glycerol and d-glyceraldehyde were also released into the medium. 9. Aerobically, fructose generated high concentrations of glycolytic intermediates. 10. Anaerobic production of lactate from fructose (74mumol/h per g dry wt.) was slower than the aerobic rate. 11. In both anaerobic and aerobic conditions the ratio [lactate]/[pyruvate] in kidney or medium was lower during perfusion with fructose than with glucose. 12. These results are discussed in terms of the regulation of renal carbohydrate metabolism.

Metabolism of Isolated Kidney Tubules

“…Portenhauser and Wieland [22] demonstrated an activation of pyruvate dehydrogenase in liver mitochondria upon addition of ADP up to 60°/, ofthe total enzyme activity. Although a rapid fall in the ATP/ADP ratio has been found after large doses of fructose and glycerol in the kidney cortex in vivo [27] and after fructose in the perfused rat kidney [28] this could hardly explain the observed increase in pyruvate dehydrogenase activity after dihydroxyacetone and glucose, since almost no change in adenine nucleotides occured after addition of these substrates [27]. On the other hand fructose, glycerol and dihydroxyacetone but not glucose led to a 4 to 10-fold increase in intracellular pyruvate concentrations [27,28], which itself can increase pyruvate dehydrogenase activity [22, 23,26,29].…”

Biochemical Aspects of Renal Ammonia Formation in Metabolic Acidosis

“…It is not due to an increase in the concentration of glutamine in the arterial blood which reaches the kidney, and is thus intrinsic to the kidney, as was first shown in isolated kidney cortex preparations [36] and has been confirmed many times since [4], e.g., in the perfused rat kidney [15] (table I). Although isolated medulla preparations can produce ammonia, this process is more abundant in the cortex; medullary metabolism does not adapt during acidosis [37], although there is a moderate decline in the rate of glycolysis [38], The adaptation of cortical ammonia production in acidosis does not occur in herbivores, in which renal ammonia production is low [39][40][41].…”

Fuel selection by the kidney: adaptation to starvation

“…Under acidotic conditions, flux through glutamine synthetase has been found to be decreased in the rat kidney in vivo (Damian & Pitts, 1970) and glutamine synthesis from glutamate is also decreased in the isolated perfused rat kidney (Hems, 1972). Together with the stimulation of unidirectional glutamine utilization, this may contribute to the increased net glutamine utilization observed in the kidney of starved rats (Elhamri et al 1993).…”

“…1967; Bowman, 1970;Cohen et al 1977;Bartlett et al 1984). Also, rat kidney (Damian & Pitts, 1970;Hems, 1972) contains significant activities of both glutamine synthetase (Richterich & Goldstein, 1958;Lemieux et al 1976;Burch et al 1978a), the enzyme responsible for glutamine synthesis, and phosphate-activated glutaminase (Richterich & Goldstein, 1958;Curthoys & Lowry, 1973), which initiates the degradation of glutamine. Since the renal activity of P-hydroxybutyrate dehydrogenase is high (Robinson & Williamson, 1980), acetoacetate and P-hydroxybutyrate are readily interconverted in whole rat kidney (Goldstein et af.…”

“…Inhibition of glutamine utilization and, therefore, of glutamine oxidation by P-hydroxybutyrate in the fed state observed by Goldstein et al (1980Goldstein et al ( , 1982 is probably reduced in the starved state because, under ketotic conditions, the rat kidney does not appear to be sensitive to the inhibitory effects of ketone bodies. Since experimental evidence obtained in the isolated perfused rat kidney suggests that the extra glutamine taken up in acidosis is accounted for by the extra glucose formed (Hems, 1972), it is likely that the 3-fold stimulation of glutamine utilization observed in vivo in the kidney of starved rats (Elhamri et al 1993) was accompanied by an enhanced contribution of glutamine to the provision of energy in the proximal tubule. Despite the presence of the enzymic machinery for glutamine metabolism and the evidence for some glutamine oxidation (Klein et al 1981;Jung et al 1989), it remains unknown whether or not significant amounts of glutamine are taken up across the basolateral membrane and oxidized in other nephron segments in vivo.…”