Glutamine‐dependent changes in gene expression and protein activity

Curi, Rui; Lagranha, Cláudia Jacques; Doi, Sonia Q.; Sellitti, Donald F.; Procópio, Joaquim; Pithon-Curi, Tânia Cristina

doi:10.1002/cbf.1165

Cited by 42 publications

(43 citation statements)

References 59 publications

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“…Moreover, depletion of particular amino acids could be a significant marker of specific cancer and therefore nutritional therapy providing deficient amino acids might be required [12][13][14]. Our results confirm the observation regarding plasma amino acids abnormalities in cancer patients [11,13].…”

Section: Discussionsupporting

confidence: 84%

Is Additional Enrichment of Diet in Branched-Chain Amino Acids or Glutamine Beneficial for Patients Receiving Total Parenteral Nutrition after Gastrointestinal Cancer Surgery?

et al. 2014

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Objectives. Total Parenteral Nutrition (TPN) is necessary in patients unable to receive oral or enteral feeding for a period of at least 7 days. branched-chain amino acids (bcaa): valine (Val), leucine (Leu), and isoleucine (Ile) are essential amino acids, which are important regulators in protein metabolism. They are also the main nitrogen source for glutamine synthesis in muscles. In this process they undergo irreversible degradation and cannot be reutilised for protein synthesis. In catabolic states, like cancers, glutamine demand increases and therefore also its utilisation, which can decrease the level of bcaa required for Gln synthesis. The purpose of this study was to evaluate the necessity of bcaa or glutamine-enriched TPN in patients after gastrointestinal cancers surgery. Material and Methods. Our aim was to investigate changes of plasma bcaa and glutamine concentrations in patients operated for colorectal, small intestine or pancreatic cancer and who are either receiving TPN or not in the postoperative period. free amino acids plasma concentrations were determined by the ion-exchange chromatography. Results. Surgery in the control group caused a decrease in Val, Ile and Leu concentrations in the postoperative period. In TPN patients this depression was inhibited beginning from the third day after surgery, except for Val and Leu in colorectal cancer group. In control and TPN patient groups, Gln concentration decreased after the surgery and subsequently increased beginning from the third day after the operation. ORIGINaL PaPeRS © copyright by Wroclaw Medical University a decrease in body mass and malnutrition are the most frequently appearing symptoms observed in gastrointestinal (GI) cancer patients with prolonged catabolic stress, and in over 60% of patients malnutrition increases with the progress of the disease. In the majority of untreated cancer patients, cachexia is observed, but the frequency of cachexia occurrence is dependent on the tumour type. as distinct from starvation, age-related loss of muscle mass, primary depression, malabsorption, and hyperthyroidism, cancerous cachexia is associated with increased morbidity [1,2]. Recent studies have shown positive effects of nutritional support in the postoperative period such as: improved protein balance, improved immune response, reduced morbidity and reduced length of hospitalization after operation [3,4].Total Parenteral Nutrition (TPN) is necessary in patients, in which postoperative complications caused an impairment in the gastrointestinal function and therefore are unable to receive and absorb oral or enteral feeding for a period longer

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Section: Discussionsupporting

confidence: 84%

Is Additional Enrichment of Diet in Branched-Chain Amino Acids or Glutamine Beneficial for Patients Receiving Total Parenteral Nutrition after Gastrointestinal Cancer Surgery?

et al. 2014

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“…Physiological concentrations of glutamine in the small intestine are reported to be ϳ1 mmol/l (11,16,27); supplementation of glutamine at 1 mmol/l showed a significant increase in RIE-1 cell proliferation and was therefore used for all subsequent experiments (data not shown).…”

Section: Glutamine Supplementation Stimulates Cell Growth and Preventmentioning

confidence: 99%

Molecular mechanisms contributing to glutamine-mediated intestinal cell survival

Larson¹,

Li²,

Chung³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…While PMA induces membrane translocation of p47 phox in control neutrophils, this agonist fails to activate p47 phox in G6pc3 Ϫ/Ϫ neutrophils. In conclusion, the decrease in the expression and activation of NADPH oxidase results in impairment of the respiratory burst activity in G6pc3 Ϫ/Ϫ neutrophils.The expression of NADPH oxidase subunits can be stimulated by glutamine 45,46 and peroxisome proliferators-activated receptoralpha (PPAR-␣). 47 In neutrophils, glutamine stimulates the expression of NADPH oxidase subunits gp91 phox , p22 phox , and p47 phox and is important for ROS production.…”

mentioning

confidence: 99%

Lack of glucose recycling between endoplasmic reticulum and cytoplasm underlies cellular dysfunction in glucose-6-phosphatase-β–deficient neutrophils in a congenital neutropenia syndrome

Jun

Lee

Cheung

et al. 2010

Blood

137

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G6PC3 deficiency, characterized by neutropenia and neutrophil dysfunction, is caused by deficiencies in the endoplasmic reticulum (ER) enzyme glucose-6-phosphatase-␤ (G6Pase-␤ or G6PC3) that converts glucose-6-phosphate (G6P) into glucose, the primary energy source of neutrophils. Enhanced neutrophil ER stress and apoptosis underlie neutropenia in G6PC3 deficiency, but the exact functional role of G6Pase-␤ in neutrophils remains unknown. We hypothesized that the ER recycles G6Pase-␤-generated glucose to the cytoplasm, thus regulating the amount of available cytoplasmic glucose/ G6P in neutrophils. Accordingly, a G6Pase-␤ deficiency would impair glycolysis and hexose monophosphate shunt activities leading to reductions in lactate production, adenosine-5-triphosphate (ATP) production, and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. Using annexin V-depleted neutrophils, we show that glucose transporter-1 translocation is impaired in neutrophils from G6pc3 ؊/؊ mice and G6PC3-deficient patients along with impaired glucose uptake in G6pc3 ؊/؊ neutrophils. Moreover, levels of G6P, lactate, and ATP are markedly lower in murine and human G6PC3-deficient neutrophils, compared with their respective controls. In parallel, the expression of NADPH oxidase subunits and membrane translocation of p47 phox are down-regulated in murine and human G6PC3-deficient neutrophils. The results establish that in nonapoptotic neutrophils, G6Pase-␤ is essential for normal energy homeostasis. A G6Pase-␤ deficiency prevents recycling of ER glucose to the cytoplasm, leading to neutrophil dysfunction. (Blood. 2010;116(15):2783-2792) IntroductionThere are 2 enzymatically active glucose-6-phosphatases (G6Pases), the liver/kidney/intestine-restricted G6Pase-␣ (or G6PC) 1,2 and the ubiquitously expressed G6Pase-␤ (also known as G6PC3). 3,4 Both enzymes are transmembrane endoplasmic reticulum (ER) proteins, with a similar topology, that places their active site on the luminal side of the ER membrane. 5,6 Both have similar kinetic properties 2,4 and hydrolyze glucose-6-phosphate (G6P) to glucose and phosphate when coupled with the ubiquitously expressed G6P transporter (G6PT) that translocates G6P from the cytoplasm into the lumen of the ER. 7,8 The primary role of the G6Pase/G6PT complex is to provide glucose and phosphate to the ER lumen. The G6Pase-␣/G6PT complex maintains blood glucose homeostasis between meals by hydrolyzing G6P to glucose in the terminal step of gluconeogenesis and glycogenolysis. 1,2 Deficiencies in G6Pase-␣ cause glycogen storage disease type Ia (GSD-Ia) and deficiencies in G6PT result in GSD type Ib (GSD-Ib). 1,2,9 Both GSD-Ia and GSD-Ib patients manifest a phenotype of disturbed blood glucose homeostasis with GSD-Ib patients also suffering neutropenia and neutrophil dysfunction, 1,9 reflecting a role of G6PT in tissues beyond the liver and kidney.The biologic roles of G6Pase-␤ and the G6Pase-␤/G6PT complex are poorly defined. Neutrophils, which express both G6Pase-␤ and G6PT, 10 are capable ...

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Glutamine‐dependent changes in gene expression and protein activity

Cited by 42 publications

References 59 publications

Is Additional Enrichment of Diet in Branched-Chain Amino Acids or Glutamine Beneficial for Patients Receiving Total Parenteral Nutrition after Gastrointestinal Cancer Surgery?

Is Additional Enrichment of Diet in Branched-Chain Amino Acids or Glutamine Beneficial for Patients Receiving Total Parenteral Nutrition after Gastrointestinal Cancer Surgery?

Molecular mechanisms contributing to glutamine-mediated intestinal cell survival

Lack of glucose recycling between endoplasmic reticulum and cytoplasm underlies cellular dysfunction in glucose-6-phosphatase-β–deficient neutrophils in a congenital neutropenia syndrome

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