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)

In the rat liver acinus area synthesis and glutaminase activity are predominantly localized in the periportal area, whereas glutamine synthetase activity and the transport system for glutamate in the plasma membrane are perivenous. Detoxification of ammonium ions at low concentrations occurs exclusively by glutamine synthesis, but not by urea formation. Therefore, the two pathways of ammonia detoxification in the liver acinus represent the sequence of a low-affinity, but high-capacity system (urea synthesis) and a high-affinity system (glutamine synthesis). In agreement with this finding, obtained in experiments with the metabolically- and structurally-intact perfused rat liver, is also an almost complete inhibition of perivenous glutamine synthesis without impairment of periportal urea synthesis. This was shown after induction of a perivenous liver cell necrosis following CCl4 pretreatment with the consequence of a diminished hepatic ammonia extraction. Periportal glutaminase and perivenous glutamine synthetase are simultaneously active, resulting in an intercellular (as opposed to intracellular) glutamine cycle, being under the control of hormones, pH and portal ammonia and glutamine concentrations. The intercellular glutamine cycle provides an effective means for almost complete conversion of portal ammonium ions to urea by additional substrate supply of periportal urea synthesis, by periportal glutamine degradation and by the perivenous re-synthesis of glutamine from ammonia which escaped urea synthesis. Because urea synthesis, in contrast to glutamine synthesis, is a major pathway for the removal of bicarbonate, the switching of ammonia detoxification from urea synthesis to glutamine synthesis in acidosis or vice versa in alkalosis points to an important role of the liver in maintaining pH homeostasis. The acid-base-induced changes of the route of hepatic ammonia detoxification and therefore bicarbonate removal are performed by the regulatory properties of the enzymes of the intercellular glutamine cycle.
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PMID:Functional hepatocyte heterogeneity in ammonia metabolism. The intercellular glutamine cycle. 286 84

Catabolism of protein produces CO2, NH4+, and HCO3-. Mammals readily lose CO2 through the lungs, but the bicarbonate produced in metabolism of a typical diet (in humans, approximately 1 mol/day from approximately 100 g of protein) would cause alkalosis if not disposed of. Air-breathing animals solve this problem by incorporating NH4+ into organic compounds in which N is not protonated; thus each NH4+ ion loses a proton in the course of the synthesis. These protons serve to titrate HCO3-. In mammals, ureagenesis is the pathway by which protons are liberated from NH4+. The rate of ureagenesis therefore determines the rate of disposal of bicarbonate, and must be an important factor in the maintenance of pH homeostasis. Ammonium ion that is not needed for urea synthesis is packaged into glutamine by the liver. Hepatic glutamine synthetase is localized in the last rank of cells around the pericentral venule; thus glutamine synthetase cannot compete for NH4+ or interfere with the control of pH by urea synthesis. Ammonium excretion in the urine does not represent excretion of acid, and is not stoichiometrically related to renal generation of bicarbonate. The quantitatively major processes by which the HCO3-/CO2 ratio, and hence the pH, is regulated in blood and interstitial fluid are excretion of CO2 through the lungs and disposal of HCO3- as a consequence of ureagenesis in the liver.
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PMID:Metabolic aspects of the regulation of systemic pH. 329 86

This study was performed to evaluate the effect of lactose induced diarrhea on the key enzymes of glutamine metabolism in skeletal muscle and small intestine, in rats. As compared to weight paired controls, animals with diarrhea presented higher muscle glutamine synthetase activity associated with reduced skeletal muscle glutamine concentration with a fall in arterial glutamine and an increased intestinal glutaminase activity. These alterations are similar to those reported by others in conditions in which accelerated muscle proteolysis is likely to occur such as in sepsis and after surgery. Besides the data suggestive of an overall alterations in glutamine metabolism, an important finding of this study was the increase in specific activity of intestinal phosphate dependent glutaminase in rats with diarrhea. This enzyme has been shown not to respond to many conditions such as acidosis, alkalosis or increased glutamine ingestion through drinking water or diet.
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PMID:Effect of lactose induced diarrhea on intestinal glutaminase and muscle glutamine synthetase activities in rats. 790 81

The metabolism of (5-15N)glutamine and (2-15N) glutamine has been studied by isolated hepatocytes obtained from either control, chronically acidotic, or alkalotic rats. The main goal was to elucidate the mechanism(s) by which altered acid-base state affects hepatic ureagenesis from glutamine. Isolated hepatocytes were incubated in Krebs buffer (pH 7.4) supplemented with 0.1 mM ornithine plus either 1 mM (5-15N)glutamine or (2-15N)glutamine. To elucidate the role of glutamine cycling in net ammonia metabolism, a separate series of experiments were performed with 1 mM unlabeled glutamine plus 1 mM (15N)H4Cl. Net glutamine utilization was significantly lower in hepatocytes obtained from chronically acidotic rats compared with control or alkalotic rats. The sum of the rates of 15NH3 and (15N)urea production from (5-15N)glutamine was decreased in acidosis compared with alkalosis. After incubations of 50 min, approximately 75, 65, or 90% of the N in carbamoyl-phosphate was derived from the 5-N of glutamine in control, acidosis, or alkalosis respectively. In experiments with (2-15N)glutamine, the production of singly and doubly labeled (15N)urea as well as (15N)aspartate and (15N)H3 was significantly smaller in acidosis compared with alkalosis. Furthermore, a correlation was observed between production rates of (15N)aspartate and (15N)urea, suggesting that alterations in urea production may depend on aspartate formed from glutamine. However, the production of (15N)alanine was higher in acidosis compared with alkalosis with apparent correlation between the production of (15N)alanine and 2-oxoglutaramate, a product of the glutamine aminotransferase pathway. In addition, the rate of glutamine recycling was significantly higher in acidosis compared with control or alkalosis, indicating that both flux through glutamine aminotransferase and flux through glutamine synthetase were elevated in acidosis compared with alkalosis. These data suggest that decreased formation of aspartate from glutamine may limit ureagenesis in chronic metabolic acidosis. The formation of aspartate may depend on the availability of oxaloacetate rather than diminished flux through transaminase reaction. The enhancement of alanine production and glutamine synthesis may provide an alternate route of N disposal in cases of diminished urea formation.
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PMID:Acid-base regulation of hepatic glutamine metabolism and ureagenesis: study with 15N. 843 54

Experimental metabolic alkalosis is known to stimulate whole-animal urea production and active ion secretion by the rectal gland in the dogfish shark. Furthermore, recent evidence indicates that a marked alkaline tide (systemic metabolic alkalosis) follows feeding in this species and that the activities of the enzymes of the ornithine-urea cycle (OUC) for urea synthesis in skeletal muscle and liver and of energy metabolism and ion transport in the rectal gland are increased at this time. We therefore evaluated whether alkalosis and/or NaCl/volume loading (which also occurs with feeding) could serve as a signal for activation of these enzymes independent of nutrient loading. Fasted dogfish were infused for 20 h with either 500 mmol L(-1) NaHCO3 (alkalosis + volume expansion) or 500 mmol L(-1) NaCl (volume expansion alone), both isosmotic to dogfish plasma, at a rate of 3 mL kg(-1) h(-1). NaHCO3 infusion progressively raised arterial pH to 8.28 (control = 7.85) and plasma [HCO3-] to 20.8 mmol L(-1) (control = 4.5 mmol L(-1)) at 20 h, with unchanged arterial P(CO2), whereas NaCl/volume loading had no effect on blood acid-base status. Rectal gland Na+,K+-ATPase activity was increased 50% by NaCl loading and more than 100% by NaHCO3 loading, indicating stimulatory effects of both volume expansion and alkalosis. Rectal gland lactate dehydrogenase activity was elevated 25% by both treatments, indicating volume expansion effects only, whereas neither treatment increased the activities of the aerobic enzymes citrate synthase, NADP-isocitrate dehydrogenase, or the ketone body-utilizing enzyme beta-hydroxybutyrate dehydrogenase in the rectal gland or liver. The activity of ornithine-citrulline transcarbamoylase in skeletal muscle was doubled by NaHCO3 infusion, but neither treatment altered the activities of other OUC-related enzymes (glutamine synthetase, carbamoylphosphate synthetase III). We conclude that both the alkaline tide and salt loading/volume expansion act as signals to activate some but not all of the elevated metabolic pathways and ionoregulatory mechanisms needed during processing of a meal.
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PMID:Is the alkaline tide a signal to activate metabolic or ionoregulatory enzymes in the dogfish shark (Squalus acanthias)? 1841 54