Rat muscle branched-chain ketoacid dehydrogenase activity and mRNAs increase with extracellular acidemia

England, Brian K.; Greiber, S.; Mitch, William E.; Bowers, Blair; Herring, W J; McKean, Martha C.; Ebb, R. G.; Price, S. Russ; Danner, Dean J.

doi:10.1152/ajpcell.1995.268.6.c1395

Cited by 61 publications

(34 citation statements)

References 18 publications

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“…In our study, leucine oxidation rates across the kidney tended to be lower in acidemic subjects, indicating that amino acid oxidation is not increased by metabolic acidosis in the kidney, in agreement with studies showing no change in branched-chain ketoacid dehydrogenase activity in the kidneys of acidotic rats (30,31).…”

Section: Discussionsupporting

confidence: 92%

Kidney Protein Dynamics and Ammoniagenesis in Humans with Chronic Metabolic Acidosis

Garibotto

Asioli²,

Robaudo³

et al. 2004

Journal of the American Society of Nephrology

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Abstract. To evaluate the effects of chronic metabolic acidosis on protein dynamics and amino acid oxidation in the human kidney, a combination of organ isotopic ( 14 C-leucine) and mass-balance techniques in 11 subjects with normal renal function undergoing venous catheterizations was used. Five of 11 studies were performed in the presence of metabolic acidosis. In subjects with normal acid-base balance, kidney protein degradation was 35% to 130% higher than protein synthesis, so net protein leucine balance was markedly negative. In acidemic subjects, kidney protein degradation was no different from protein synthesis and was significantly lower (P Ͻ 0.05) than in controls. Kidney leucine oxidation was similar in both groups. Urinary ammonia excretion and total ammonia production were 186% and 110% higher, respectively, and more of the ammonia that was produced was shifted into urine (82% versus 65% in acidemic subjects versus controls). In all studies, protein degradation and net protein balance across the kidney were inversely related to urinary ammonia excretion and to the partition of ammonia into urine, but not to total ammonia production, arterial pH, , urinary flow, the uptake of glutamine by the kidney, or the ammonia released into the renal veins. The data show that response of the human kidney to metabolic acidosis includes both changes in amino acid uptake and suppression of protein degradation. The latter effect, which is likely induced by the increase in ammonia excretion and partition into the urine, is potentially responsible for kidney hypertrophy.Both in vitro and in vivo studies in animals have shown that metabolic acidosis causes several biochemical and morphologic changes in tubule cells, which are ultimately associated with kidney hypertrophy (1,2). Protein synthesis and degradation, the determinants of protein metabolism, are key factors in the hypertrophy process. However, information regarding the signals and mechanisms by which metabolic acidosis might cause kidney hypertrophy is still incomplete, and whether these effects take place in the human kidney is unknown. A further complicating element is that the effects of acidosis on protein turnover rates vary in different tissue types, with catabolic events occurring in peripheral tissues and splanchnic organs (3,4).Chronic acidosis causes several metabolic alterations in the renal proximal tubule, including increased H ϩ secretion (1,5), ammonia synthesis (6), and citrate reabsorption (6,7). These changes in tubule function are associated with changes in the activities of a number of proteins, including the apical membrane Na ϩ /H ϩ antiporter (7), glutaminase and glutamate dehydrogenase (8), and phosphoenolpyruvate carboxykinase (9), which may affect intracellular substrate availability for protein turnover, amino acid metabolism and/or transport, and gluconeogenesis. It has been shown that in tubule epithelial cells, the associated increase in ammonia production, rather than the acidosis per se, is responsible for favoring tubular hyper...

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Section: Discussionsupporting

confidence: 92%

Kidney Protein Dynamics and Ammoniagenesis in Humans with Chronic Metabolic Acidosis

Garibotto

Asioli²,

Robaudo³

et al. 2004

Journal of the American Society of Nephrology

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“…Metabolic acidosis causes accelerated proteolysis by enhancing the activity of ATP-dependent ubiquitin-proteasome system (28) and the enzyme branch-chain ketoacid dehydrogenase (29). However, we found that bicarbonate supplement improved SGA score for anorexia and NPNA.…”

Section: Discussioncontrasting

confidence: 58%

Oral Sodium Bicarbonate for the Treatment of Metabolic Acidosis in Peritoneal Dialysis Patients

Szeto

Wong

Chow

et al. 2003

Journal of the American Society of Nephrology

120

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“…The ingestion of 0.28 M of NH 4 Cl for 10 days markedly decreased aortic blood-pH values and serum-bicarbonate concentrations ( Table 1), indicating that a metabolic acidosis was caused by this treatment, like previous results in other experimental chronic acidosis experiments (2,15). No significant differences were detected in weight and intake between the two experimental groups.…”

Section: Resultssupporting

confidence: 79%

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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Rat muscle branched-chain ketoacid dehydrogenase activity and mRNAs increase with extracellular acidemia

Cited by 61 publications

References 18 publications

Kidney Protein Dynamics and Ammoniagenesis in Humans with Chronic Metabolic Acidosis

Kidney Protein Dynamics and Ammoniagenesis in Humans with Chronic Metabolic Acidosis

Oral Sodium Bicarbonate for the Treatment of Metabolic Acidosis in Peritoneal Dialysis Patients

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

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