Effects of chronic uraemia on the formation of glucose and urea plus ammonia from <scp>l</scp>-alanine, <scp>l</scp>-glutamine and <scp>l</scp>-serine in isolated rat hepatocytes

Klim, R; Albajar, Marta; Hems, R.; Williamson, Dermot H.

doi:10.1042/cs0700627

Cited by 11 publications

(8 citation statements)

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“…The physiological interpretation of this observation is not entirely clear. Klim et al (37) described increased urea production from alanine or glutamine in isolated hepatocytes from uremic rats, whereas Cano et al (16) reported decreased ureagenesis from these same substrates in isolated rat hepatocytes from their uremic animals (compared with controls in both cases). Even though the experimental designs differed, it is difficult to resolve the discrepancy between these results.…”

Section: R1584 Vampire Shrew Bear and Chronic Renal Failurementioning

confidence: 99%

Vampire bat, shrew, and bear: comparative physiology and chronic renal failure

Singer

2002

American Journal of Physiology-Regulatory, Integrative and Comp

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In the typical mammal, energy flux, protein metabolism, and renal excretory processes constitute a set of closely linked and quantitatively matched functions. However, this matching has limits, and these limits become apparent when animals adapt to unusual circumstances. The vampire bat and shrew have an extremely high protein intake, and the glomerular filtration rate (GFR) is not commensurate with the large urea load to be excreted. The vampire bat is chronically azotemic (blood urea concentration 27-57 mmol/l); yet there is no information as to how this animal has adjusted to such an azotemic internal environment. A high protein intake should also lead to chronic glomerular hyperfiltration; yet neither animal appears to develop progressive renal failure. The American black bear, on the other hand, has adapted to a prolonged period without intake or urine output. Despite continued amino acid catabolism with urea production, this mammal is able to completely salvage and reutilize urea nitrogen for protein synthesis, although the signals that initiate this metabolic adaptation are not known. The vampire bat, shrew, and bear are natural models adapted to circumstances analogous to chronic renal failure. Unraveling these adaptations could lead to new interventions for the prevention/treatment of chronic renal failure.

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Section: R1584 Vampire Shrew Bear and Chronic Renal Failurementioning

confidence: 99%

Vampire bat, shrew, and bear: comparative physiology and chronic renal failure

Singer

2002

American Journal of Physiology-Regulatory, Integrative and Comp

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“…In cultured hepatocytes from normal and diabetic rats a relationship was found between glucose production and the activity of serine dehydratase (Mak & Pitot, 1981). Klim et al (1986) reported that the activity of serine dehydratase increases with an increase in the plasma glucagon/insulin ratio in vivo. There is evidence, however, that the activities of both serine dehydratase and serine transaminase increase in diabetes (Rowsell et al, 1973;Snell, 1984).…”

Section: Turnover Of Glycine and Serinementioning

confidence: 99%

“…Seine was shown to be glycogenic in isolated rat hepatocytes, but whereas more alanine is taken up than serine, a larger fraction of utilized serine is converted into glucose (Klim et al, 1986). Two pathways of serine catabolism are glucogenic: conversion by deamination into pyruvate, catalysed by serine dehydratase, and into hydroxypyruvate by transamination, catalysed by serine: pyruvate aminotransferase.…”

Section: Turnover Of Glycine and Serinementioning

confidence: 99%

Gluconeogenesis from glycine and serine in fasted normal and diabetic rats

Hetenyi

Anderson

Raman

et al. 1988

Biochemical Journal

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1. Non-anaesthetized normal and diabetic rats were fasted for 1 day, and [U-14C]glycine, or [U-14C]serine, or [U-14C]- plus [3-3H]-glucose was injected intra-arterially. The rates of synthesis de novo/irreversible disposal for glycine, serine and glucose, as well as the contribution of carbon atoms by the amino acids to plasma glucose, were calculated from the integrals of the specific-radioactivity-versus-time curves in plasma. 2. The concentrations of both glycine and serine in blood plasma were lower in diabetic than in fasted normal animals. 3. The rates of synthesis de novo/irreversible disposal of both amino acids tended to be lower in diabetic animals, but the decrease was statistically significant only for serine (14.3 compared with 10.5 mumol/min per kg). 4. Of the carbon atoms of plasma glucose, 2.9% arose from glycine in both fasted normal and diabetic rats, whereas 4.46% of glucose carbon originated from serine in fasted normal and 6.77% in diabetic rats. 5. As judged by their specific radioactivities, plasma serine and glycine exchange carbon atoms rapidly and extensively. 6. It was concluded that the turnover of glycine remains essentially unchanged, whereas that of serine is decreased in diabetic as compared with fasted normal rats. The plasma concentration of both amino acids was lower in diabetic rats. Both glycine and serine are glucogenic. In diabetic rats the contribution of carbon atoms from glycine to glucose increases in direct proportion to the increased glucose turnover, whereas the contribution by serine becomes also proportionally higher.

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“…The key regulatory enzymes of ureagenesis and gluconeogenesis are located in the same zone of hepatic acinus, showing a parallel behavior of these pathways. Therefore, in the situations of high blood-urea concentrations, gluconeogenesis, in general (18), and from serine, in particular (27), are stimulated; meanwhile, when urea production is inhibited, gluconeogenesis (9) and even serine dehydratase also decrease. This relationship leads us to assume some degree of channeling between substrates and initial products of both pathways; for example, the carbon backbone of amino acids that give up their NH 3 group for urea synthesis is channelled to glucose production.…”

Section: Discussionmentioning

confidence: 99%

Downregulation in the expression of the serine dehydratase in the rat liver during chronic metabolic acidosis

López-Flores

Peragón²,

Valderrama³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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. Downregulation in the expression of the serine dehydratase in the rat liver during chronic metabolic acidosis. Am J Physiol Regul Integr Comp Physiol 291: R1295-R1302, 2006. First published June 22, 2006 doi:10.1152/ajpregu.00095.2006.-Blood pH controls the activity of important regulatory enzymes in the metabolism. Serine dehydratase (SerDH) transforms L-serine into pyruvate and ammonium and is involved in the regulation of gluconeogenesis from serine in the rat liver. In this work, we investigate the effect of chronic metabolic acidosis on the kinetics, specific protein level, tissue location, and mRNA levels of rat liver SerDH. Experimental acidosis was induced in rats by ingestion of 0.28 M ammonium chloride solution for 10 days. Acidosis significantly (P Ͻ 0.05) decreased SerDH activity at all substrate concentrations assayed. Moreover, the V max value was 38.50 Ϯ 3.51 mU/mg (n ϭ 7) of mitochondrial protein in the acidotic rats and 92.49 Ϯ 6.79 mU/mg (n ϭ 7) in the control rats. Western blot analysis revealed a significant reduction (14%) in the level of SerDH protein content in the rat liver during acidosis. Immunohistochemical analysis showed that SerDH location did not change in response to chronic metabolic acidosis and confirmed previous results on SerDH protein levels. Moreover, the SerDH mRNA level, estimated by RT-PCR, was also significantly 33.8% lower than in control. These results suggest that during experimental acidosis a specific repression of rat-liver SerDH gene transcription could result, lowering the amount and activity of this enzyme. The changes found in SerDH expression are part of an overall metabolic response of liver to maintain acid-base homeostasis during acidosis. NH 4Cl; reverse transcriptase-polymerase chain reaction; serine catabolism ACIDOSIS IS A METABOLIC STATE in which, for different causes, blood pH and bicarbonate fall. In these cases, the organism attempts to compensate for these imbalances by increasing the respiratory frequency or adapting its metabolism to facilitate the removal of protons via renal excretion and thus restore the serum-bicarbonate level. For this, major metabolic adaptations occur in liver and kidney. During this situation, liver metabolism helps maintain the acid-base balance by controlling the ammonium supply to kidney in the form of glutamine (1, 21, 50). In parallel, amino-acid breakdown (34, 42) and gluconeogenesis (9, 26) are also regulated. In this situation, the hepatic synthesis of urea and glucose are inhibited, and glutamine metabolism shifts to the net release of this amino acid to serum (1,21,50). In kidney, the fall in blood pH values intensifies the catabolism of glutamine and gluconeogenesis (26). The increased glutamine catabolism increases the renal excretion of protons in the form of ammonium and gluconeogenesis as one end pathway of the metabolism of the carbon backbone of glutamine. These changes are due to an induction of glutaminase, glutamate dehydrogenase, and phosphoenolpyruvate carboxykinase (PEPCK) during this situation ...

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Effects of chronic uraemia on the formation of glucose and urea plus ammonia from l-alanine, l-glutamine and l-serine in isolated rat hepatocytes

Cited by 11 publications

References 0 publications

Vampire bat, shrew, and bear: comparative physiology and chronic renal failure

Vampire bat, shrew, and bear: comparative physiology and chronic renal failure

Gluconeogenesis from glycine and serine in fasted normal and diabetic rats

Downregulation in the expression of the serine dehydratase in the rat liver during chronic metabolic acidosis

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