glutaminase and Body-Weight

The liver plays a critical role in maintaining ammonia homeostasis. Urea cycle defects, liver injury, or failure and glutamine synthetase (GS) deficiency result in hyperammonemia, serious clinical conditions, and lethality. In this study we used a mouse model with a defect in the urea cycle enzyme ornithine transcarbamylase (Otcspf-ash) to test the hypothesis that glucagon receptor inhibition using a monoclonal blocking antibody will reduce the hyperammonemia and associated lethality induced by a high-protein diet, which exacerbates disease. We found reduced expression of glutaminase, which degrades glutamine and increased expression of GS in livers of Otcspf-ash mice treated with the glucagon receptor blocking antibody. The gene expression changes favor ammonia consumption and were accompanied by increased circulating glutamine levels and diminished hyperammonemia. Otcspf-ash mice treated with the glucagon receptor-blocking antibody gained lean and body mass and had increased survival. These data suggest that glucagon receptor inhibition using a monoclonal antibody could reduce the risk for hyperammonemia and other clinical manifestations of patients suffering from defects in the urea cycle, liver injury, or failure and GS deficiency.

Topics: Amino Acids; Ammonia; Animals; Antibodies, Monoclonal; Body Weight; Gene Expression Regulation; Glutamate-Ammonia Ligase; Glutaminase; Hyperammonemia; Male; Mice; Ornithine Carbamoyltransferase; Ornithine Carbamoyltransferase Deficiency Disease; Receptors, Glucagon

As a highly toxic environmental pollutant, methylmercury (MeHg) can cause neurotoxicity in animals and humans. Considering the antioxidant property of grape seed proanthocyanidin extracts (GSPE), this study was aimed to evaluate the effect of GSPE on MeHg-induced neurotoxicity in rats. Rats were exposed to MeHg by intraperitoneal injection (4, 12 μmol/kg, respectively) and GSPE was administered by gavage (250 mg/kg) 2 h later. After a 4-week treatment, phosphate-activated glutaminase, glutamine synthetase, glutathione peroxidase and superoxide dismutase activities, glutamate, glutamine, malondialdehyde and glutathione contents in cerebral cortex were measured. Reactive oxygen species (ROS) and apoptosis were also estimated in cells. The results showed that the MeHg-induced neurotoxicity was significantly attenuated. GSPE significantly decreased the production of ROS, counteracted oxidative damage and increased the antioxidants and antioxidant enzymes activities in rats prior to MeHg exposure. Moreover, the effects on the rate of apoptotic cells and the disturbance of glutamate homeostasis were correspondingly modulated. These observations highlighted the potential of GSPE in offering protection against MeHg-induced neurotoxicity.

Topics: Animals; Antioxidants; Apoptosis; Body Weight; Cells, Cultured; Cerebral Cortex; Flow Cytometry; Glutamate-Ammonia Ligase; Glutaminase; Glutathione; Glutathione Peroxidase; Grape Seed Extract; Injections, Intraperitoneal; Malondialdehyde; Methylmercury Compounds; Neurotoxicity Syndromes; Proanthocyanidins; Rats; Rats, Wistar; Reactive Oxygen Species; Superoxide Dismutase; Weight Gain

Protein-glutaminase (PG) is a protein-deamidating enzyme produced from the microorganism Chryseobacterium proteolyticum strain 9670. Food safety studies were conducted on both the enzyme and the production organism. The strain was evaluated for pathogenicity and toxigenicity by intravenous and oral inoculation studies in Slc:ICR male SPF mice. The results demonstrate that the tested C. proteolyticum strain is of very low pathogenicity comparable to known food source bacterial strains and is very unlikely to demonstrate any pathogenicity in animals or humans. The level of endotoxin is very low and typical of the endotoxin levels in drinking water and teas. A 90-day study of PG, conducted in Sprague-Dawley rats, showed no adverse effects due to the enzyme up to dose levels of 2500 mg/kg-bw/day (NOAEL). Details of the study are presented, including, organ and body weights, histological findings, and blood and urine chemistry. Additionally, bacterial reverse mutation test (Ames test) and chromosomal aberration test using mammalian established cell line were conducted, resulting in the absence of mutagenicity in PG.

Topics: Administration, Oral; Animals; Bacterial Proteins; Blood Chemical Analysis; Body Weight; CHO Cells; Chromosome Aberrations; Chryseobacterium; Cricetinae; Cricetulus; Dose-Response Relationship, Drug; Female; Glutaminase; Hematologic Tests; Injections, Intravenous; Longevity; Male; Mice; Mice, Inbred ICR; Mutagenicity Tests; Mutagens; No-Observed-Adverse-Effect Level; Rats; Rats, Sprague-Dawley; Salmonella typhimurium

A better knowledge of intestinal adaptation after resection is required to improve the nutritional support that is given to patients. The aim of this study was to understand the metabolic changes underlying early adaptation after massive intestinal resection.. Rats were assigned to either 80% intestinal resection or transection. All animals received the same intragastric nutrition. On day 8, plasma glutamine turnover was measured. Substrate use was determined on isolated enterocytes that were incubated in the presence of D-[U-(14)C] glucose (2 mmol/L), L-[U-(14)C] glutamine (2 mmol/L), L-[U-(14)C] arginine (1 mmol/L), or L-[1-(14)C] ornithine (1 mmol/L).. Plasma glutamine turnover was similar in both groups. The rate of enterocyte glutamine use was significantly increased in the resection group, although the maximal glutaminase activity was unchanged. Glutathione generation was enhanced 3-fold in remnant intestine as compared with transected intestine (P <.05). L-ornithine decarboxylation was increased markedly in resected animals (P <.05), without any detectable change of maximal ornithine decarboxylase activity.. The early phase of intestinal adaptation after resection induces changes in enterocyte glutamine and ornithine metabolism that may be related, in part, to increased de novo polyamine synthesis. This observation suggests that a supplementation of artificial nutrition by nutrients that lead to the generation of trophic agents may be of potential interest.

Topics: Adaptation, Physiological; Animals; Arginine; Arteries; Body Weight; Cell Separation; Citrulline; Decarboxylation; Enterocytes; Glutaminase; Glutamine; Glutathione; Intestine, Small; Intestines; Male; Ornithine; Ornithine Decarboxylase; Rats; Rats, Wistar

In this study the enzyme glutaminase, purified from the ascites fluid of ovarian cancer patients, was analysed for its antiangiogenic activity. Intraperitoneal administration of this enzyme reduces the number of tumor directed capillaries in solid and ascites tumor bearing Swiss mice induced by transplantation of Ehrlich ascites cells. The enzyme has a critical role in regulating the secretion of vascular endothelial growth factor (VEGF) from tumor cell and in turn tumor growth. Glutamine analogue like 6-diazo, 5- oxo L-norleucine (DON) is also found to be effective in regulating vascular endothelial growth factor (VEGF) secretion from tumor cells in vitro. Treatment with enzyme reduced serum VEGF levels of the tumor induced animals. In vitro VEGF production by EAC cells was reduced in a concentration dependent manner in presence of glutamine analogue.

Topics: Animals; Antineoplastic Agents; Body Weight; Carcinoma, Ehrlich Tumor; Cell Line, Tumor; Cell Proliferation; Diazooxonorleucine; Dose-Response Relationship, Drug; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; Glutaminase; Glutamine; Mice; Neoplasm Transplantation; Neoplasms; Neovascularization, Pathologic; Ovarian Neoplasms; Time Factors; Vascular Endothelial Growth Factor A

After synaptic release, glutamate is taken up by the nerve terminal via a plasma membrane-associated protein termed excitatory amino acid transporter 3 (EAAT3). Following entry into the nerve terminal, glutamate is pumped into synaptic vesicles by a vesicular transport system. Three different vesicular glutamate transporter proteins (VGLUT1-3) representing unique markers for glutamatergic neurons were recently characterized. The presence of EAAT3, glutaminase and VGLUT1-3 was examined in mouse, rat and rabbit species at mRNA and protein levels in hypothalamic neurons which are involved in the regulation of body weight using in situ hybridization and immunohistochemistry. EAAT3 and glutaminase mRNAs were demonstrated in all parts of the arcuate nucleus in the dorsomedial and ventromedial hypothalamic nuclei and lateral hypothalamic area. VGLUT1 mRNA was present in the magnocellular lateral hypothalamic nucleus. VGLUT2 mRNA was demonstrated in a subpopulation of neurons in the arcuate nucleus and in the ventromedial and dorsomedial hypothalamic nuclei and lateral hypothalamic area. Few VGLUT3 mRNA expressing neurons were scattered throughout the medial and lateral hypothalamus. EAAT3-like immunoreactivity (-li) was demonstrated in glutamate, neuropeptide Y (NPY), agouti-related peptide (AGRP), pro-opiomelanocortin (POMC), cocaine and amphetamine-regulated transcript (CART), melanin-concentrating hormone and orexin-immunoreactive (-ir) neurons. VGLUT2-li could only be demonstrated in POMC- and CART-ir neurons of the ventrolateral arcuate nucleus. The results show that key neurons involved in regulation of energy balance are glutamatergic and/or densely innervated by glutamatergic nerve terminals. Whereas orexigenic NPY/AGRP neurons situated in the ventromedial part of the arcuate nucleus are mainly GABAergic, it is shown that several anorexigenic POMC/CART neurons of the ventromedial arcuate nucleus are most likely glutamatergic [corrected].

Topics: Agouti-Related Protein; Amino Acid Transport System X-AG; Amino Acid Transport Systems, Acidic; Animals; Body Weight; Carrier Proteins; Cell Membrane; Cyclohexanes; DNA-Binding Proteins; Excitatory Amino Acid Transporter 3; Glutamate Plasma Membrane Transport Proteins; Glutaminase; Hypothalamus; Immunohistochemistry; In Situ Hybridization; Intercellular Signaling Peptides and Proteins; Intracellular Signaling Peptides and Proteins; Male; Membrane Transport Proteins; Mice; Mice, Inbred C57BL; Nerve Tissue Proteins; Neurons; Neuropeptide Y; Neuropeptides; Orexins; Pro-Opiomelanocortin; Proteins; Rabbits; Rats; Rats, Sprague-Dawley; RNA, Messenger; Species Specificity; STAT3 Transcription Factor; Symporters; Synaptic Vesicles; Trans-Activators; Vesicular Glutamate Transport Protein 1; Vesicular Glutamate Transport Protein 2; Vesicular Glutamate Transport Proteins; Vesicular Transport Proteins

Glutamine is the major respiratory fuel and energy source of the rapidly proliferating tumor cells and that is why glutamine clearance by glutaminase therapy provides an opportunity to fight against the neoplasm. Glutaminase from bacterial source was tried on experimental models but had to be excluded because of its limited efficacy. Search for a better glutaminase continued exploiting the mammalian sources. In the present study, glutaminase purified from human ovarian cancer ascites fluid was used in experimental solid and ascites mice model alone and in combination with Cu-Sulphate and heparin. Cumulative findings indicate that the enzyme alone is quite effective in lowering tumor burden and reducing not only the tumor induced angiogenesis, but also an angiogenic inducer, heparin mediated angiogenesis. However, the presence of Cu with the enzyme, amplified the antineoplastic response by improving anti-angiogenic potential and hematological status of the tumor bearing host. Therefore, Cu-glutaminase combination strengthened the hypothesis that together they may provide a better therapeutic regimen in experimental mice tumor model.

Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Ascitic Fluid; Blood Cell Count; Body Weight; Copper; Drug Therapy, Combination; Female; Glutaminase; Heparin; Humans; Male; Mice; Neoplasms, Experimental; Neovascularization, Pathologic; Ovarian Neoplasms; Spleen

The consumption of soy and soy products (including soy sauce) has been increasing in Western countries due to purported health benefits of soy (cancer protective, estrogenic effects). In addition to providing soy proteins and isoflavones, soy sauce also functions as a flavor enhancer and is able to impart a "umami" taste. Glutaminases are used in the production of soy sauce and enzymatically hydrolyzed protein. The glutaminases described herein were produced from the cultured broth of Cryptococcus albidus (ATCC-20293) which is designated as CK, a mutant of C. albidus (ATCC-20293) which is designated as CK-D10 and the newly isolated Cryptococcus sp. NISL-3771 which is designated as TK. All three preparations (CK, CK-D10 and TK) were evaluated for pathogenicity and virulence in mice and were found to be non-pathogenic. The acute LD(50)s for CK in male mice was greater than 4.8 g/kg body weight and for female mice was greater than 6.5 g/kg body weight. Acute LD(50)s for CK and CK-D10 in male and female rats was greater than 7.5 g/kg body weight, and that for TK was greater than 10 g/kg body weight. Subchronic (90-day) feeding studies (wherein the glutaminases were presented as dietary admixtures) were conducted in mice and rats. The NOAEL for CK in mice was 7.5 g/kg body weight/day. The NOAELs in rats were as follows: for CK, 9 g/kg body weight/day; for CK-D10, 1.2 g/kg body weight/day, and for TK, 8 g/kg body weight/day. Mice received CK as a dietary admixture at levels of 0, 1.0 and 10.0% for 1 year. The NOAEL was 13 g/kg body weight/day. The glutaminases from C. albidus described herein demonstrate very low toxicity.

Topics: Animals; Body Weight; Cryptococcosis; Cryptococcus; Female; Glutaminase; Lethal Dose 50; Male; Mice; No-Observed-Adverse-Effect Level; Rats; Rats, Inbred F344; Rats, Wistar; Survival Rate

Chronic treatment of rats from postnatal day 6 to 25 with drugs that interact with the N-methyl-D-aspartate (NMDA) receptor induced a differential effect on the activity of some enzymes involved in neurotransmitter synthesis. Two of these drugs ((5R,10S)-(+)-5-methyl-10,11 -dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine hydrogen maleate (MK-801) and 3-(2-carboxypiperazin-4-yl)propyl-1phosphonic acid (CPP)) caused a marked reduction (20-40%) of glutaminase and aspartate aminotransferase activity in the cerebellum. These changes were observed only at a very precise time of development (i.e. 10 to 19 postnatal day). The competitive antagonist, amino phosphonovaleric acid (APV), did not affect any of the enzymes studied at all tested ages. When animals were treated with NMDA only a slight, but significant, increase in the activity of glutaminase was observed at 9-11 postnatal day only. Any of the agonists or antagonists tested significantly affected the activity of lactate dehydrogenase as compared to control animals. Histologic observations of cerebella treated with the indicated drugs showed that only MK-801, and CPP to a lesser extent, induced a small reduction in the width of the internal granule layer. The body weight of animals treated with MK-801 was clearly reduced, but only in more mature rats (> 16 postnatal day), when animals did not show any alteration in the enzymes tested. These results support the suggestion that presynaptic influences, particularly from glutamatergic neurons, are critical to promote cerebellar granule neurons differentiation during critical periods of the cerebellar development.

Topics: 2-Amino-5-phosphonovalerate; Age Factors; Animals; Aspartate Aminotransferases; Body Weight; Cell Differentiation; Cerebellum; Cerebral Cortex; Dizocilpine Maleate; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Female; Glutaminase; L-Lactate Dehydrogenase; Male; Nerve Fibers; Nerve Tissue Proteins; Neurons; Organ Specificity; Piperazines; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Synaptic Transmission

Chronic renal failure (CRF) is associated with a sundry of abnormalities in pancreatic islets including a rise in their cytosolic calcium, reduced ATP content, and impaired glucose-induced insulin secretion. The latter is also stimulated by amino acids (such as leucine), and the cellular processes involved in leucine-induced insulin secretion are different from those responsible for glucose-induced insulin release. The present study examined whether leucine-induced insulin secretion is also impaired in CRF and investigated the cellular derangements for such a potential abnormality. The results showed that leucine-induced insulin secretion is markedly reduced by islets from CRF animals, and this defect was prevented by parathyroidectomy (PTX) of the CRF animals or by their treatment with verapamil, an agent that blocks the action of parathyroid hormone (PTH) on the pancreatic islets. Both leucine uptake and alpha-ketoisocaproic acid-induced insulin secretion by islets from CRF rats are normal; however, both the activation of glutamate dehydrogenase (GLDH) by leucine or by 2-aminobicyclo-[2-2-1]-haptene and the utilization of alpha-ketoglutarate are impaired, and the maximal reaction rate (Vmax) of glutaminase is reduced. These derangements are corrected by PTX of CRF rats or by their treatment with verapamil. The data demonstrate that 1) CRF is associated with impaired leucine-induced insulin secretion, 2) this defect is due to the state of secondary hyperparathyroidism of CRF, and 3) the cellular derangements responsible for this defect involve abnormalities in the metabolism of leucine and derangements in the leucine-GLDH-alpha-ketoglutarate-glutaminase pathway of the islets.

Topics: Animals; Body Weight; Bridged Bicyclo Compounds; Creatinine; Glutamate Dehydrogenase; Glutaminase; In Vitro Techniques; Insulin; Insulin Secretion; Islets of Langerhans; Keto Acids; Kidney Failure, Chronic; Kinetics; Leucine; Nephrectomy; Parathyroid Hormone; Parathyroidectomy; Rats; Rats, Sprague-Dawley; Reference Values; Time Factors; Verapamil

Previous reports of our laboratory have shown that w-6 PUFA-rich diets (UC) given to rats during 6 weeks causes important changes of the metabolism of the lymphoid organs. In this study, the effect of saturated fatty acids-rich diet (SC) and also the persistence of the changes caused by (UC) were investigated during ageing (14 months). The major changes previously reported for UC fed rats, during 6 weeks, fully persisted when this feeding condition was maintained for 14 months. Moreover, the SC group also showed modifications of the activities of key enzymes of glucose and glutamine metabolism of the lymphoid organs with ageing. Both groups fed fatty acids-rich diets markedly reduced the rate of lipogenesis in the liver, spleen, and thymus in contrast to slight changes reported for 6 weeks. These results suggest that fatty acids-rich diets, by causing important metabolic alterations, may pronounce the impairment of the immune function observed during ageing.

Topics: Aging; Animals; Blood Glucose; Body Weight; Cholesterol; Citrate (si)-Synthase; Fatty Acids; Fatty Acids, Unsaturated; Glucosephosphate Dehydrogenase; Glutaminase; Hexokinase; Immune Tolerance; Lipids; Lymph Nodes; Lymphatic System; Male; Organ Size; Rats; Rats, Wistar

Intramuscular glutamine falls with injury and disease in circumstances associated with increases in blood corticosteroids. We have investigated the effects of corticosteroid administration (0.44 mg/kg dexamethasone daily for 8 days, 200 g female rats) on intramuscular glutamine and Na+, muscle glutamine metabolism and sarcolemmal glutamine transport in the perfused hindlimb. After dexamethasone treatment intramuscular glutamine fell by 45% and Na+ rose by 25% (the respective muscle/plasma distribution ratios changed from 8.6 to 4.5 and 0.12 to 0.15); glutamine synthetase and glutaminase activities were unchanged at 475 +/- 75 and 60 +/- 19 nmol/g muscle per min. Glutamine output by the hindlimb of anaesthetized rats was increased from 31 to 85 nmol/g per min. Sarcolemmal glutamine transport was studied by paired-tracer dilution in the perfused hindlimb: the maximal capacity (Vmax) for glutamine transport into muscle (by Na(+)-glutamine symport) fell from 1058 +/- 310 to 395 +/- 110 nmol/g muscle per min after dexamethasone treatment, accompanied by a decrease in the Km (from 8.1 +/- 1.9 to 2.1 +/- 0.4 mM glutamine). At physiological plasma glutamine concentration (0.75 mM) dexamethasone appeared to cause a proportional increase in sarcolemmal glutamine efflux over influx. Addition of dexamethasone (200 nM) to the perfusate of control rat hindlimbs caused acute changes in Vmax and Km of glutamine transport similar to those resulting from 8-day dexamethasone treatment. The reduction in muscle glutamine concentration after dexamethasone treatment may be primarily due to a reduction in the driving force for intramuscular glutamine accumulation, i.e., in the Na+ electrochemical gradient. The prolonged increase in muscle glutamine output after dexamethasone treatment (which occurs despite a reduction in the size of the intramuscular glutamine pool) appears to be due to a combination of (a) accelerated sarcolemmal glutamine efflux and (b) increased intramuscular synthesis of glutamine.

Topics: Amino Acids; Animals; Biological Transport, Active; Body Weight; Dexamethasone; Female; Glutamate-Ammonia Ligase; Glutaminase; Glutamine; Muscles; Perfusion; Rats; Rats, Inbred Strains; Regional Blood Flow; Sarcolemma; Sodium

The changes in the activities of ammonia-metabolizing enzymes in liver and brain after ethanol intoxication has been investigated in rats. After administration of ethanol 30% (w/v) 6g kg-1 for 4 weeks we found an increase in liver glutamate dehydrogenase and glutaminase activity. In brain tissue the glutaminase activity was significantly higher and glutamate dehydrogenase was significantly lower. Glutamine synthetase activity in liver and brain was practically unchanged. The reasons for these changes in the activities of some ammonia-metabolizing enzymes in liver and brain after ethanol ingestion have been discussed.

Topics: Ammonia; Animals; Appetite; Body Weight; Brain; Ethanol; Glutamate Dehydrogenase; Glutamate-Ammonia Ligase; Glutaminase; Liver; Male; Rats; Rats, Inbred Strains; Reference Values

Forty-eight tumor-free mice and 32 mice bearing Ehrlich ascites tumor were randomized into 2 treatments, Acinetobacter glutaminase-asparaginase (AGA) (600 IU/kg/day for 7 days) and 0.9% NaCl controls, and into 2 or 3 isocaloric diets, normal protein (NP) (20 g protein/100 g diet), high protein (HP) (58 g protein/100 g diet), and zero protein (ZP) (tumor-free mice only). In tumor-free, NP-fed mice, AGA caused percentage reductions (P less than 0.01) in the nitrogen content of liver (50%), intestine (42%), thymus (89%), spleen (75%), and carcass (20%), but HP prevented this effect on intestine and carcass and caused percentage increases in the nitrogen content of liver (53%), intestine (36%), thymus (122%), and carcass (25%). In Ehrlich ascites tumor mice (NP or HP fed) AGA caused markedly lower (P less than 0.01) tumor burdens and increased nitrogen content of intestine (HP), kidney (NP and HP), and spleen (NP and HP). Ehrlich ascites tumor, AGA-treated, HP-fed mice ate 31% less food (P less than 0.01) (compared to NP) but HP resulted in percentage increases in the nitrogen content of liver (18%; P = 0.05), intestine (25%; P less than 0.05), and thymus (164%; P less than 0.01). In the Ehrlich ascites tumor, AGA group the HP diet caused higher hematocrit and serum total protein (both, P less than 0.05). Adverse nutritional effects of AGA seen in normal mice were markedly diminished in tumor-bearing animals. The observed nitrogen-sparing effects of the high protein: energy ratio may be relevant to humans and to other forms of neoplasia and chemotherapy.

Topics: Acinetobacter; Animals; Asparaginase; Body Weight; Carcinoma, Ehrlich Tumor; Dietary Proteins; Eating; Female; Glutaminase; Leukocyte Count; Mice; Mice, Inbred Strains; Nitrogen

Topics: Amino Acids; Animals; Body Weight; Brain; DNA; Female; Glutamate Decarboxylase; Glutamate-Ammonia Ligase; Glutamates; Glutaminase; Glutamine; Nerve Tissue Proteins; Organ Size; Pregnancy; Protein Deficiency; Rats; RNA

In order to study the influence of hypercapnia on the content of glutamate and glutamine in the developing brain, pregnant rats and their offspring were kept in CO2 rich (6-10%) atmosphere and the litters were killed at different ages between 4 and 28 days. In the hypercapnic rats the content of both amino acids in the brain increases with age with almost the same time course as in normocapnic rats. At any age the glutamate content is lower in the hypercapnic animals than in control rats, whereas the glutamine content, beyond the first 8 days of life is increased. Both effects are rapidly reversible on return to air breathing. Although the glutamate-glutamine system is in full development, the influence of hypercapnia can be compared to that observed in adult rats. Hypercapnia did not change the glutaminase and the glutamine synthetase activity of the brain.

Topics: Aging; Animals; Animals, Newborn; Body Weight; Brain; Carbon Dioxide; Glutamate-Ammonia Ligase; Glutamates; Glutaminase; Glutamine; Hypercapnia; Organ Size; Rats

The activities of renal lactate and malate dehydrogenases, glutaminase, and Na-K-ATPase were determined in aging male C57BL/6 mice. Urine concentrating ability in these mice and renal response to metabolic acidosis were also studied. Total enzyme activities were measured in vitro in tissue homogenates from mice that were 120, 400, 500, 600, 700, and 800 days old. Urine concentrating ability was determined in these mice prior to sacrifice. Lactate and malate dehydrogenase activities decreased between 120 and 700 days with only male dehydrogenase activity increasing between 700 and 800 days. Age did not affect glutaminase or Na-K-ATPase activities and urine concentrating ability was decreased only at 700 days. Both urine ammonia excretion and renal glutaminase activity increased at 120 and 600 days in response to metabolic acidosis. However, only 5 of 12 animals tested at 600 days survived the acid stress for a full 7 days.

Topics: Acidosis; Adenosine Triphosphatases; Aging; Ammonia; Animals; Body Weight; Glutaminase; Kidney; Kidney Concentrating Ability; L-Lactate Dehydrogenase; Liver; Magnesium; Malate Dehydrogenase; Male; Mice; Mice, Inbred C57BL; Organ Size; Potassium; Sodium; Testis

Acinetobacter glutaminase-asparaginase (AGA) and Escherichia coli asparaginase were compared for their effects on plasma and tissue levels of amino acids, ammonia, and glutamyl transferase activity in the mouse. Free asparagine was depleted similarly in plasma and tissues by both enzymes. AGA treatment produced partial depletion of glutamine concentrations in muscle, spleen, small intestine, and liver. Brain and kidney glutamine concentrations actually rose with treatment. Despite over 100-fold increase in plasma glutamate, only the kidney showed a substantial increase in free glutamate levels during AGA treatment. Glutamine biosynthesis measured by glutamyl transferase activity showed an appreciable increase only in the kidney. Ammonia levels in tissues and plasma rose 1.3- to 4.3-fold. In general, E. coli asparaginase treatment had much less effect on these measurements than did AGA. The changes in these levels are discussed in relation to sites of possible toxicity and antitumor effects.

Topics: Acetyltransferases; Acinetobacter; Amino Acids; Ammonia; Animals; Asparaginase; Asparagine; Aspartic Acid; Body Weight; Brain; Escherichia coli; Female; Glutamates; Glutaminase; Glutamine; Kidney; Mice; Organ Size; Serine; Spleen; Threonine

Topics: Acetates; Amino Acid Metabolism, Inborn Errors; Ammonia; Animals; Body Weight; Dietary Proteins; Disease Models, Animal; Glutaminase; Liver; Lysine; Quaternary Ammonium Compounds; Time Factors

Topics: Alanine; Alcaligenes; Amino Acid Isomerases; Amino Acid Oxidoreductases; Animals; Aspartate Aminotransferases; Bacillus; Body Weight; Carcinoma, Ehrlich Tumor; Cattle; Glutamate Dehydrogenase; Glutaminase; Isoenzymes; Ketoglutaric Acids; Kinetics; Leucine; Liver; Lysine; Mice; Pseudomonas; Pseudomonas aeruginosa; Time Factors; Transaminases

Topics: Acute Disease; Amino Acids; Animals; Asparaginase; Blood; Body Weight; Chromatography, Ion Exchange; Chronic Disease; Diet; Escherichia coli; Female; Glutaminase; Glutamine; L-Lactate Dehydrogenase; Leukemia, Experimental; Mice; Neoplasm Transplantation; RNA Viruses; Virus Diseases

Topics: Adrenal Glands; Adrenalectomy; Alcohol Oxidoreductases; Animals; Body Weight; Diet; Dietary Carbohydrates; Fructose; Fumarates; Glucose; Glucose-6-Phosphatase; Glutaminase; Glycerolphosphate Dehydrogenase; Hydro-Lyases; Hypophysectomy; Isomerases; L-Lactate Dehydrogenase; L-Serine Dehydratase; Liver; Liver Glycogen; Lyases; Malate Dehydrogenase; Male; Nucleoside Diphosphate Sugars; Organ Size; Oxidoreductases; Pentosephosphates; Pituitary Gland; Proteins; Rats; Transferases; Uracil Nucleotides

Topics: Alanine Transaminase; Amino Acids; Animals; Animals, Newborn; Aspartate Aminotransferases; Biological Assay; Body Weight; Brain; Brain Chemistry; Carboxy-Lyases; Discrimination Learning; DNA; Glutamate Dehydrogenase; Glutaminase; Nutrition Disorders; Organ Size; Rats; RNA; Transaminases

Topics: Animals; Body Weight; Carbonates; Chlorides; Glutaminase; Growth; Hydrochloric Acid; Magnesium; Potassium; Poultry; Sodium

Topics: Ammonia; Biochemical Phenomena; Biochemistry; Body Weight; Cold Temperature; Fluids and Secretions; Glutaminase; Kidney; Organ Size; Rats; Research; Urine

Topics: Alanine Transaminase; Arginase; Body Weight; Cold Temperature; Feeding and Eating Disorders; Glucose-6-Phosphatase; Glutaminase; Hyperphagia; Hypothalamus; Liver; Organ Size; Physiology; Rats; Research

Topics: Animals; Arginase; Body Weight; Cold Temperature; Glutaminase; Growth Hormone; Liver; Nitrogen; Oxidoreductases; Rats; Transaminases

Topics: Alanine Transaminase; Aspartate Aminotransferases; Body Weight; Cold Temperature; D-Alanine Transaminase; Glucose-6-Phosphatase; Glutaminase; Liver; Pharmacology; Rats; Research; Thyroid Gland; Thyroid Hormones