Glutamine Metabolism in Metabolic Acidosis

Alleyne, George A.O.; Lupiáñez, José A.; McFarlane‐Anderson, Norma; Hortelano, Paloma; Benjamin, Jacqueline M.; Barnswell, Jennifer; Scott, B.W.

doi:10.1002/9780470720691.ch6

Cited by 5 publications

(1 citation statement)

References 46 publications

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“…Mitochondrial glutamine metabolism was initially studied in renal, skeletal muscular, intestinal and brain physiology as a major player in nitrogen metabolism (Kovacevic and McGivan, 1983). For example, kidney proximal tubular epithelium upregulates glutaminolysis to extrude more NH 4 + as acid equivalent under pathological chronic metabolic acidosis (Alleyne et al, 1982). Recently, more research has focused on the increased glutaminolysis activity in cancer cells after metabolic reprogramming, as glutaminolysis provides an additional source of biosynthetic precursors as well as energy for rapidly dividing cancer cells (Jin et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Glutaminolysis is Essential for Energy Production and Ion Transport in Human Corneal Endothelium

Zhang

Ogando

et al. 2017

EBioMedicine

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Corneal endothelium (CE) is among the most metabolically active tissues in the body. This elevated metabolic rate helps the CE maintain corneal transparency by its ion and fluid transport properties, which when disrupted, leads to visual impairment. Here we demonstrate that glutamine catabolism (glutaminolysis) through TCA cycle generates a large fraction of the ATP needed to maintain CE function, and this glutaminolysis is severely disrupted in cells deficient in NH3:H+ cotransporter Solute Carrier Family 4 Member 11 (SLC4A11). Considering SLC4A11 mutations leads to corneal endothelial dystrophy and sensorineural deafness, our results indicate that SLC4A11-associated developmental and degenerative disorders result from altered glutamine catabolism. Overall, our results describe an important metabolic mechanism that provides CE cells with the energy required to maintain high level transport activity, reveal a direct link between glutamine metabolism and developmental and degenerative neuronal diseases, and suggest an approach for protecting the CE during ophthalmic surgeries.

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Section: Discussionmentioning

confidence: 99%

Glutaminolysis is Essential for Energy Production and Ion Transport in Human Corneal Endothelium

Zhang

Ogando

et al. 2017

EBioMedicine

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Metabolic adaptation of renal carbohydrate metabolism. V.In vivo response of rat renal-tubule gluconeogenesis to different diuretics

et al. 1994

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We have studied the effects of the diuretics mersalyl, furosemide and ethacrynic acid on renal gluconeogenesis is isolated rat-kidney tubules and on the activities of the most important gluconeogenic and glycolytic enzymes in both fed and fasted rats. Mersalyl (15 mg.kg-1 animal weight) significantly decreased the rate of gluconeogenesis in well-fed rats (68%) as well as in 24 and 48-h fasted ones (33 and 37% respectively). This inhibition occurred when lactate, pyruvate, glycerol or fructose were used as substrates. Ethacrynic acid at a dose of 50 mg.kg-1 animal weight provoked a transient inhibition of renal glucose production by almost 20% but only in fed rats with lactate as substrate, whereas the same dose of furosemide did not affect this metabolic pathway. Parallel to these changes, mersalyl caused a significant inhibition in the maximum activity of the most important gluconeogenic enzymes, phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase and glucose 6-phosphatase, in both fed and fasted rats. Neither ethacrynic acid nor furosemide produced any variations in the activities of these enzymes. The activity of the glycolytic enzymes phosphofructokinase and pyruvate kinase was not modified by these diuretics. Nevertheless, the activity of the thiol-enzyme glyceraldehyde 3-phosphate dehydrogenase was severely inhibited by mersalyl and to a lesser extent by the other diuretics. This inhibition was higher in fasted than fed rats. Hence, we conclude that the inhibitory effect of mersalyl on renal gluconeogenesis is due, at least partly, to a decrease in the flux through the gluconeogenic enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

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The regulation of phosphate-activated glutaminase activity and glutamine metabolism in the streptozotocin-diabetic rat

Watford

Smith

Erbelding

1984

Biochemical Journal

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The activity of phosphate-activated glutaminase was increased in the kidney, liver and small intestine of rats made diabetic for 6 days with injection of streptozotocin (75 mg/kg body wt.). Insulin prevented this increase in all three tissues. Treatment with NaHCO3, to correct the acidosis that accompanies diabetes, prevented the increase in renal glutaminase activity, but not that in liver or small intestine. Chemically induced acidosis (NH4Cl solution as drinking water) or alkalosis (NaHCO3 solution as drinking water) increased and decreased, respectively, glutaminase activity in the kidney, but were without significant effect on the activity in liver and small intestine. The increase in glutaminase activity in the small intestine during diabetes was due to an overall increase in the size of this organ, and was only detectable when activity was expressed in terms of whole organ, not mucosal scrapings or isolated enterocytes. Prolonged diabetes (40 days) resulted in an even greater increase in the size and glutaminase activity of the small intestine. Despite this marked increase in capacity for glutamine catabolism, arteriovenous-difference measurements showed a complete suppression of plasma glutamine utilization by the small intestine during diabetes, confirming the report by Brosnan, Man, Hall, Colbourne & Brosnan [(1983) Am. J. Physiol. 235, E261-E265].

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Glutamine Metabolism in Metabolic Acidosis

Cited by 5 publications

References 46 publications

Glutaminolysis is Essential for Energy Production and Ion Transport in Human Corneal Endothelium

Glutaminolysis is Essential for Energy Production and Ion Transport in Human Corneal Endothelium

Metabolic adaptation of renal carbohydrate metabolism. V.In vivo response of rat renal-tubule gluconeogenesis to different diuretics

The regulation of phosphate-activated glutaminase activity and glutamine metabolism in the streptozotocin-diabetic rat

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