Rapidly proliferating cancer cells require energy and cellular building blocks for their growth and ability to maintain redox balance. Many studies have focused on understanding how cancer cells adapt their nutrient metabolism to meet the high demand of anabolism required for proliferation and maintaining redox balance. Glutamine, the most abundant amino acid in plasma, is a well-known nutrient used by cancer cells to increase proliferation as well as survival under metabolic stress conditions. In this review, we provide an overview of the role of glutamine metabolism in cancer cell survival and growth and highlight the mechanisms by which glutamine metabolism affects cancer cell signaling. Furthermore, we summarize the potential therapeutic approaches of targeting glutamine metabolism for the treatment of numerous types of cancer.
Cell Survival ; Glutamine ; Metabolism ; Oxidation-Reduction ; Plasma ; Stress, Physiological

Wound is the most fundamental issue of burn injury, and its repair depends not only on effective wound treatment, but also on the good nutritional status of burned patients. Nutrition support is an important means to improve the nutritional status of patients and promote wound healing, and how to make it match the metabolism of burn wounds is a difficult task of nutrition therapy. In this paper, we analyzed the metabolic characteristics of different stages in burn wound healing, focused on the metabolic characteristics of glucose, protein, and glutamine in these stages, and proposed a nutritional strategy that is compatible with wound healing in order to maximize the role of nutrition therapy in wound repair.
Burns/therapy* ; Glutamine ; Humans ; Nutritional Support ; Proteins/metabolism* ; Wound Healing

Mouse follicular oocytes, denuded and intact, were cultured in pyruvate salt sol and glutamine salt sol supplemented bovine serum albumin to compare the maturation rate. Glutamine has no effect on maturation of the denuded mouse oocyte but has an effect on maturation of the intact oocyte by increasing the maturation rate, depending on the increased concentration of glutamine (0.4 mM to 2 mM). Changes in osmolarity of the operation medium from 280 mOsm to 310 mOsm has no discernible effect on the oocyte maturation. A high frequency of abnormal 1st polar bodies was observed in pyruvate salt sol. and this may be due to the increased energy source in the cytoplasm of the 1st polar body when the po1ar body was extruded into the perivitelline space after the 1st meiosis.
Animal ; Cell Division ; Female ; Glutamine/metabolism ; In Vitro ; Mice ; Oocytes/cytology ; Oocytes/metabolism* ; Ovum/metabolism* ; Pyruvates/metabolism

Mouse follicular oocytes, denuded and intact, were cultured in pyruvate salt sol and glutamine salt sol supplemented bovine serum albumin to compare the maturation rate. Glutamine has no effect on maturation of the denuded mouse oocyte but has an effect on maturation of the intact oocyte by increasing the maturation rate, depending on the increased concentration of glutamine (0.4 mM to 2 mM). Changes in osmolarity of the operation medium from 280 mOsm to 310 mOsm has no discernible effect on the oocyte maturation. A high frequency of abnormal 1st polar bodies was observed in pyruvate salt sol. and this may be due to the increased energy source in the cytoplasm of the 1st polar body when the po1ar body was extruded into the perivitelline space after the 1st meiosis.
Animal ; Cell Division ; Female ; Glutamine/metabolism ; In Vitro ; Mice ; Oocytes/cytology ; Oocytes/metabolism* ; Ovum/metabolism* ; Pyruvates/metabolism

OBJECTIVEEndotoxemia is a serious syndrome resulting in multi-organ failure. Once it happens, the penetration of small intestine epithelium increases, body liquid losses, then effective circulating blood decreases and serious metabolic acidosis, serious hypotension, systolic failure, and even shock may occur. In this pathological process, endotoxin, tumor necrosis alpha and systolic dysfunction play important roles. Nowadays, many studies have been done to resolve the systolic dysfunction, but too much attention had been paid to the followings: the depressions of myocardium caused by tumor necrosis alpha, other inflammatory factors, endotoxin and metabolic acidosis; the disturbance of blood vessel-nerve regulations; nitric oxide (NO)/inducible nitric oxide synthase (iNOS) over-synthesis and the decreased density of beta-receptors in the myocardium and/or their activities. Little attention has been paid to the relationship between alpha sarcmeric actin (alpha-SA) and systolic dysfunction during endotoxemia. Glutamine (Gln) can be metabolized into glutathione, an eliminator of free radical. It has been used in preventing myocardial damage from reperfusion. This study aimed to observe the dynamic changes of alpha-SA and mRNA expressions in rats with endotoxemia and examine the effects of Gln on them.

METHODSClassical rat model of endotoxemia was established by intraperitoneal injection of LPS (4 mg/kg, Escherichia coli O55:B5, Sigma). 121 Wistar 18-day-rats were divided into three groups randomly, (1) 0 h control group (normal saline: 1 ml/kg, n = 11). (2) LPS group (LPS: 4 mg/kg, n = 55). (3) Gln group (LPS: 4 mg/kg and immediately 13.64%; Gln: 1 ml/kg, Fresenus, n = 55), Furthermore, LPS and Gln groups were divided into 2, 4, 6, 24 and 72 h time points (n = 11). Each time point of LPS and Gln as well as control rats were anaesthetized at each time point with 1% chloral hydrate injected intraperitoneally at the dosage of 1 ml/kg. Then rats were sacrificed at appoint time, and the hearts were isolated. Eight of them were put in 76 degrees C liquid nitrogen and then frozen in minute 80 degrees C icebox in order to measure the expression of alpha-SA mRNA by RT-PCR. Three of them were fixed in 4% formaldehydum polymerisatum for 12 to 16 h, then the expression of alpha-SA was detected by immunohistochemistry.

RESULTS(1) Compared to 0 h, the expressions of alpha-SA and mRNA in LPS group were significantly depressed (P < 0.01). In LPS group, the lowest was at 6 - 24 h, while in Gln group, it was postponed to 24 h. At 72 h, there was no difference in expressions of alpha-SA between Gln and 0 h group (P > 0.05). (2) Comparing at same time point, the expressions of alpha-SA were significant higher in Gln group than those in LPS group, while the expressions of alpha-SA mRNA in Gln group were high at 4-72 h. There was, however, no significant difference at early phase (P > 0.05).

CONCLUSIONAlpha-SA and its mRNA expression were depressed in LPS-induced endotoxemia, especially from 6 to 24 h. It could damage the systolic function. alpha-SA decrease in endotoxemia was due to the inhibited synthesis other than the promoted degradation. Glutamine could inhibit the effects of LPS on both alpha-SA and its mRNA expressions.

Actins ; metabolism ; Animals ; Endotoxemia ; metabolism ; Glutamine ; pharmacology ; Lipopolysaccharides ; Myocardium ; metabolism ; RNA, Messenger ; metabolism ; Rats ; Rats, Wistar

Child ; Digestive System ; metabolism ; Glutamine ; metabolism ; Humans ; Immune System ; metabolism ; Nutritional Physiological Phenomena ; physiology

OBJECTIVETo study the feasibility of non-invasive magnetic resonance spectroscopy (MRS) in measuring glutamine (GLN) level in Zelanian rabbits' skeletal muscle.

METHODSNon-invasive MRS was used to get the data of peak height ratio of GLN + glutamic acid (GLx) at 3.8 ppm and creatine (Cr) at 3.0 ppm, peak area ratio of GLx at 3.8 ppm and Cr at 3.0 ppm. High performance liquid chromatography (HPLC) was used to examine the actual GLx levels of muscle from 22 Zelanian rabbits. The feasibility of MRS was then evaluated by HPLC method.

RESULTSThe ratio of peak height and peak area of GLx and Cr by means of MRS were 0.162 +/- 0.045 and 0.092 +/- 0.065, respectively. The average concentration of GLx in skeletal muscle by means of HPLC was (4.19 +/- 2.50) micromol/g. The ratio of GLx and plasma Cr level by means of HPLC was 4.576 -/+ 0.599. The ratio of peak height and peak area of GLx and Cr by means of MRS were correlated significantly with the ratio of concentration of GLx in skeletal muscle and plasma Cr by means of HPLC (r = 0.7, P = 0.001; r = 0.6, P = 0.001).

CONCLUSIONNon-invasive MRS is feasible to measure GLN level in skeletal muscle of rabbit.

Animals ; Feasibility Studies ; Glutamine ; metabolism ; Magnetic Resonance Spectroscopy ; Muscle, Skeletal ; metabolism ; Rabbits

MicroRNAs have been identified as a new class of regulatory molecules that affect many biological functions by interferring the target gene expressions. Latest studies demonstrate that microRNAs can influence many pivotal bio-processes and deeply involve in the metabolism of glucose, lipid and amino acid and biological oxidation. For glucose metabolism, microRNAs are related to insulin secretion, insulin sensitivity, glucose uptake, glycolysis, oxidation and mitochondrial function. For lipid matebolism, microRNAs can regulate the target genes related to lipid biosynthesis, catabolism and transportation. MicroRNAs can influence glutamine catabolism.
Animals ; Glucose ; metabolism ; Glutamine ; metabolism ; Humans ; Insulin ; metabolism ; Insulin Secretion ; Lipid Metabolism ; physiology ; Metabolism ; physiology ; MicroRNAs ; physiology

OBJECTIVETo study the transport of glutamine and glucose, expression of their transporters and tissue morphology in intestinal hypoperfusion.

METHODSSprague-Dawley rats were randomized to receive 60 min of intestinal hypoperfusion (superior mesenteric artery clamp) or serve as normoxic controls (celiotomy only). At the same time, jejunal loops were randomized to receive in situ perfusion of mannitol,glucose,or glutamine.Intestinal brush border membrane vesicles (BBMV) were prepared by calcium precipitation. Sodium-dependent uptake of glucose and glutamine into BBMV were quantitated by rapid mixing and filtration. Histologic examination and immunohistochemistry were performed by pathologists blinded to the groups.

RESULTSWhen compared with the control group, tissue lactate concentration of the hypoperfused group increased significantly (4.9+/-0.3 vs 3.1+/-0.2), especially in the glucose perfused groups (P<0.01). Transport and transporters of glucose in brush border, but not glutamine, decreased during hypoperfusion [(76+/-10) pmol d mg(-1) d 10 s(-1) vs (290+/-13)pmol d mg(-1) d 10 s(-1)]. Tissue structural damage was most severe in glucose perfused groups during hypoperfusion.

CONCLUSIONTransport and expression of transporters of glucose and glutamine in enteral nutrition are differently regulated under conditions of trauma and stress.

Animals ; Enteral Nutrition ; Glucose ; metabolism ; Glutamine ; metabolism ; Intestine, Small ; blood supply ; metabolism ; pathology ; Ischemia ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley

Stress conditions such as sepsis, trauma, burn, fracture, and major surgery are associated with hypermetabolism and hypercatabolism. Protein is mobilized for energy and uptake of amino acids by muscle tissue is decreased in stress conditions. The metabolic response to stress causes movement of amino acids (predominantly alanine and glutamine) from peripheral reserves to metabolically active tissues. Glutamine is a conditionally essential amino acid during stress. Glutamine plays a role in maintenance of intestinal immune function and reinforcement of wound repair. Supplementation of parenteral glutamine (0.3~0.5 g/kg/day) as a component of nutrition support may improve clinical outcomes in appropriate patients. In patients with multiorgan failure, supplementation with a high dose of glutamine (>0.5 g/kg/day) in the acute phase of critical illness is not recommended. In stress conditions, provision of adequate protein is essential and glutamine supplementation should be considered in patients without specific contraindications.
Alanine ; Amino Acids ; Burns ; Critical Illness ; Glutamine* ; Humans ; Metabolism* ; Sepsis ; Wounds and Injuries