The conversion of alanine into glutamine in guinea-pig renal cortex. Essential role of pyruvate carboxylase

Forissier, M; Baverel, Gabriel

doi:10.1042/bj2000027

Cited by 21 publications

(10 citation statements)

References 15 publications

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“…Hepatic glutamine synthetase is restricted to the perivenous hepatocytes (22). Conceivably, glutamine may be entirely formed from alanine in these cells, as it is in the guinea pig kidney (23). Alternatively, glutamate produced in the periportal cells may be released and taken up by the high affinity glutamate transporter in the perivenous hepatocytes (24).…”

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confidence: 99%

Alanine Metabolism in the Perfused Rat Liver

Brosnan¹,

Brosnan²,

Nissim³

et al. 2001

Journal of Biological Chemistry

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We have utilized [15 N]alanine or 15 NH 3 as metabolic tracers in order to identify sources of nitrogen for hepatic ureagenesis in a liver perfusion system. Studies were done in the presence and absence of physiologic concentrations of portal venous ammonia in order to test the hypothesis that, when the NH 4 ؉ :aspartate ratio is >1, increased hepatic proteolysis provides cytoplasmic aspartate in order to support ureagenesis. When 1 mM [ 15 N]alanine was the sole nitrogen source, the amino group was incorporated into both nitrogens of urea and both nitrogens of glutamine. However, when studies were done with 1 mM alanine and 0.3 mM NH 4 Cl, alanine failed to provide aspartate at a rate that would have detoxified all administered ammonia. Under these circumstances, the presence of ammonia at a physiologic concentration stimulated hepatic proteolysis. In perfusions with alanine alone, ϳ400 nmol of nitrogen/min/g liver was needed to satisfy the balance between nitrogen intake and nitrogen output. When the model included alanine and NH 4 Cl, 1000 nmol of nitrogen/min/g liver were formed from an intra-hepatic source, presumably proteolysis. In this manner, the internal pool provided the cytoplasmic aspartate that allowed the liver to dispose of mitochondrial carbamyl phosphate that was rapidly produced from external ammonia. This information may be relevant to those clinical situations (renal failure, cirrhosis, starvation, low protein diet, and malignancy) when portal venous NH 4 ؉ greatly exceeds the concentration of aspartate. Under these circumstances, the liver must summon internal pools of protein in order to accommodate the ammonia burden.

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confidence: 99%

Alanine Metabolism in the Perfused Rat Liver

Brosnan¹,

Brosnan²,

Nissim³

et al. 2001

Journal of Biological Chemistry

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“…In previous studies [1,2], we have shown that, although they contain high activities ofgluconeogenic enzymes [3] and although they form large amounts of oxaloacetate from alanine and aspartate, which are metabolized at high rates, guinea-pig kidneycortex tubules do not synthesize glucose from these substrates even after 48 h of starvation. Since glucose has been shown to be synthesized from other substrates such as lactate and pyruvate in guinea-pig renal cortex [4], this led us to consider the possibility that the synthesis of glucose from alanine or aspartate in kidney tubules could be balanced by a simultaneous high glycolytic activity.…”

Section: Introductionmentioning

confidence: 78%

Glutamine synthesis from glucose and ammonium chloride by guinea-pig kidney tubules

Michoudet¹,

Chauvin²,

Baverel³

1994

Biochemical Journal

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1. At a physiological concentration (5 mM), glucose was found to be metabolized by isolated kidney cortex tubules prepared from fed guinea pigs. 2. The release of 14CO2 from [U-14C]glucose indicated that oxidation of the glucose carbon skeleton represented about 50% of the glucose removed; significant amounts of lactate and glutamine also accumulated. 3. Addition of 0.1-10 mM NH4Cl led to a dose-dependent stimulation of glucose metabolism which was accompanied by a large increase in lactate and glutamine accumulation and, to a lesser extent, in glucose oxidation. 4. Comparison of the release of 14CO2 from [1-14C]- and [6-14C]glucose indicates that, in both the absence and the presence of NH4Cl, the pentose phosphate shunt was only a minor pathway of glucose metabolism. 5. The central role of pyruvate carboxylase in the conversion of glucose carbon into glutamine carbon was demonstrated by using a bicarbonate-free medium and measuring the fixation of 14CO2 from [14C]bicarbonate, which was recovered mostly at C-1 of glutamine plus glutamate. 6. The NH4Cl-induced stimulation of glucose removal was secondary not only to increased glutamine synthesis, as shown by the effect of methionine sulphoximine, an inhibitor of glutamine synthetase, but also to the stimulation of phosphofructokinase activity by NH4Cl. 7. Renal arterio-venous difference measurements revealed that, in vivo, the guinea-pig kidney removed glucose from the circulating blood, which suggests that glucose carbon may contribute to the carbon skeleton of the glutamine released by this organ.

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“…This coupling of gluconeogenesis to ammoniagenesis seems unique for the kidney, since renal gluconeogenesis increases in metabolic acidosis in parallel to ammoniagenesis, whereas hepatic gluconeogenesis decreases (40,41). On the other hand glutamine nitrogen can be recovered äs alanine and vice versa (42). This seems remarkable since alanine, the major hepatic glucogenic amino acid, is not used äs a glucogenic precursor by the kidney (40).…”

Section: Regulation Of Renal Ammoniagenesis and Ammonium Transportmentioning

confidence: 99%

Renal and Hepatic Nitrogen Metabolism in Systemic Acid Base Regulation

Guder

Häussinger²,

Gerok³

1987

Clinical Chemistry and Laboratory Medicine

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Summary:Renal and hepatic nitrogen metabolism are linked by an interorgan glutamine flux, coupling both renal ammoniagenesis and hepatic urea production to systemic acid-base regulation. Reconsideration of established pathways and recent observations led to a conceptional change with a movement from a twoorgan concept (lungs and kidney) of acid-base balance to a three-or-more organ concept (lungs, kidney, liver). This development implies new regulatory sites of systemic pH control and consequently a new pathophysiological understanding of derangements of acid-base homeostasis.In this new concept the urea cycle regulates the removal of metabolically generated bicarbonate during a protein load in a pH-and bicarbonate-dependent manner. This is related to a switch of hepatic ammonium detoxication from urea to glutamine synthesis in metabolic acidpsis, and vice versa in alkalosis. An adaptive increase in the renal capacity for glutamine deamidation and deamination and for ammonium excretion leads to a proportional decrease in renal urea excretion at the expense of ammonium in acidotic conditions.

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The conversion of alanine into glutamine in guinea-pig renal cortex. Essential role of pyruvate carboxylase

Cited by 21 publications

References 15 publications

Alanine Metabolism in the Perfused Rat Liver

Alanine Metabolism in the Perfused Rat Liver

Glutamine synthesis from glucose and ammonium chloride by guinea-pig kidney tubules

Renal and Hepatic Nitrogen Metabolism in Systemic Acid Base Regulation

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