Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002063 (alkalosis)
 2,286 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied mechanism(s) by which adaptations of renal TCA cycle metabolism abet ammoniagenesis from glutamine in altered acid-base states. Renal tubules from control, acidotic, or alkalotic rats were incubated at pH 7.4 with 1 mM [3-13C,5-15N]glutamine or 2 mM [3-13C]pyruvate. In acidosis there was a significantly higher flux through glutaminase and through glutamate, 2-oxoglutarate, succinate and malate dehydrogenases as well as markedly enhanced 13C-glucose formation. Alkalosis was associated with little change in 13C flux from glutamine to TCA cycle intermediates compared with control but production of 15NH3 and 13C glucose was significantly diminished. The current studies indicate that renal ammoniagenesis might be regulated at the sites of citrate synthetase (CS) and/or alpha-ketoglutarate dehydrogenase (KGDH). Thus, in chronic metabolic acidosis decreased flux through CS and increased flux through KGDH resulted in enhanced flux through glutamate dehydrogenase and glutaminase pathway. The opposite occurred in alkalosis. The data suggest that in various acid-base states the rate of renal gluconeogenesis is linearly correlated with malate efflux from the mitochondria. In renal tissue, inhibition occurs at one site of the TCA cycle there is an augmentation of fluxes through pathways beyond that site in order to maintain the respiratory process and the redox state in the mitochondria.
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PMID:Adaptation of renal tricarboxylic acid cycle metabolism to various acid-base states: study with [3-13C,5-15N]glutamine. 177 Sep 13

The renal proximal tubule contains a variety of biochemical pathways, which can metabolize glutamine, the major substrate for renal ammoniagenesis. The intramitochondrially located phosphate-dependent glutaminase (PDG) pathway, rather than the various cytosolic pathways, appears to play the predominant role in regulating the rate of renal NH3 production. Acute acidosis stimulates NH3 production by activating alpha-ketoglutarate dehydrogenase and secondarily glutamate dehydrogenase; whereas the adaptation to chronic metabolic acidosis results primarily from enhanced glutamine transport into the mitochondria and possibly increased activity of PDG. There is no adaptation of ammoniagenesis to chronic respiratory acidosis, because the proximal tubular intracellular pH is not decreased. Alkalosis suppresses NH3 formation but the precise mechanism is not clarified. Ammoniagenesis can be modulated independent of acid-base status by a variety of factors including potassium homeostasis, TCA cycle intermediates, hormones which increase cAMP, prostaglandin F2 alpha, insulin, growth hormone, angiotensin II, corticosteroids, aldosterone, and tubular flow rate.
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PMID:Biochemical pathways and modulators of renal ammoniagenesis. 228 87

Exposure to hyperoxia (500-600 torr) or low pH (4.5) for 72 h or NaHCO(3) infusion for 48 h were used to create chronic respiratory (RA) or metabolic acidosis (MA) or metabolic alkalosis in freshwater rainbow trout. During alkalosis, urine pH increased, and [titratable acidity (TA) - HCO(-)(3)] and net H(+) excretion became negative (net base excretion) with unchanged NH(+)(4) efflux. During RA, urine pH did not change, but net H(+) excretion increased as a result of a modest rise in NH(+)(4) and substantial elevation in [TA - HCO(-)(3)] efflux accompanied by a large increase in inorganic phosphate excretion. However, during MA, urine pH fell, and net H(+) excretion was 3.3-fold greater than during RA, reflecting a similar increase in [TA - HCO(-)(3)] and a smaller elevation in phosphate but a sevenfold greater increase in NH(+)(4) efflux. In urine samples of the same pH, [TA - HCO(-)(3)] was greater during RA (reflecting phosphate secretion), and [NH(+)(4)] was greater during MA (reflecting renal ammoniagenesis). Renal activities of potential ammoniagenic enzymes (phosphate-dependent glutaminase, glutamate dehydrogenase, alpha-ketoglutarate dehydrogenase, alanine aminotransferase, phosphoenolpyruvate carboxykinase) and plasma levels of cortisol, phosphate, ammonia, and most amino acids (including glutamine and alanine) increased during MA but not during RA, when only alanine aminotransferase increased. The differential responses to RA vs. MA parallel those in mammals; in fish they may be keyed to activation of phosphate secretion by RA and cortisol mobilization by MA.
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PMID:Renal responses of trout to chronic respiratory and metabolic acidoses and metabolic alkalosis. 1044 55