Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.4.1.2 (glutamate dehydrogenase)
 4,380 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic metabolic alkalosis was induced in rats drinking 0.3 M NaHCO3 and receiving 1 mg furosemide/100 g body weight per day intraperitoneally. Another group of animals received a potassium supplement in the form of 0.3 M KHCO3. In this group, hypokalemia did not develop and muscle potassium fell by only 18% versus 50% in those not receiving potassium. In vitro renal production of ammonia and uptake of glutamine fell by 40% with a decrease in the activity of glutaminase I and glutamate dehydrogenase. Activity of phosphofructokinase, a major enzyme of glycolysis, rose only in the kidney of animals receiving a potassium supplement. Fructose-1,6-diphosphatase fell as well as phosphoenolpyruvate carboxykinase. Malate dehydrogenase also fell. The activity of phosphofructokinase also rose in the liver, heart, and leg muscle. The major biochemical changes in the renal cortex were the following: glutamate, alpha-ketoglutarate, malate, lactate, pyruvate, alanine, aspartate, and citrate rose as well as calculated oxaloacetate. The concentration of intermediates like 2-phosphoglycerate, 3-phosphoglycerate, and glucose-6-phosphate fell. The cytosolic redox potential (NAD+/NADH) decreased. In addition to the fall in ammoniagenesis, it could be demonstrated in vitro that the renal tubules incubated with glutamine showed decreased glucose production and increased production of lactate and pyruvate. The concentration of lactate was elevated in all tissues examined including liver, heart, and leg muscle. This study confirms in the rat that decreased renal ammoniagenesis takes place following decreased uptake of glutamine in metabolic alkalosis. All other changes are accounted for by the process of increased glycolysis, which appears to take place in all tissues in metabolic alkalosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal tissue metabolism in the rat during chronic metabolic alkalosis: importance of glycolysis. 294 66

To investigate the mechanisms of the antiammoniagenic effect of ketone bodies, acidotic dogs (NH4Cl) were infused with either beta-hydroxybutyrate or acetoacetate. Total blood ketones ranged from 2 to 4 mM. Renal ammoniagenesis fell by a mean of 53%, with a proportional decrease in glutamine extraction. Glutamate release in the renal vein rose, renal extraction of lactate fell, and aspartate and alanine production decreased. Study of the metabolite profile of the renal cortex by the freeze-clamp technique before and after ketone infusion showed that tissue glutamine concentration was unchanged, whereas glutamate, alpha-ketoglutarate, malate, and citrate rose. The intermediates of the gluconeogenic pathway, such as phosphoenolypyruvate, 2-phosphoglycerate, 3-phosphoglycerate, and glucose-6-phosphate, fell significantly. The redox state as calculated from the free NAD+/NADH ratios in the cytosolic (lactate dehydrogenase) and the mitochondrial (glutamate dehydrogenase and beta-hydroxybutyrate dehydrogenase) compartments was reduced. The present study suggests that ketone bodies inhibit renal ammoniagenesis through increased generation of alpha-ketoglutarate (metabolic or bicarbonate effect) and a decrease in the mitochondrial and cytosolic redox potentials in the kidney.
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PMID:Cellular mechanisms of the antiammoniagenic effect of ketone bodies in the dog. 743 17