Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.4.1.2 (glutamate dehydrogenase)
 4,380 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is well established that caloric restriction extends life span and significantly retards the rate of occurrence of most age-associated degenerative disease processes. A paucity of data exists relative to the mechanisms by which caloric restriction accomplishes these events. We have examined the effect of caloric restriction in rats on several hepatic enzymes of intermediary metabolism. The activities of glycolytic and supporting enzymes including lactate dehydrogenase, pyruvate kinase, sorbitol dehydrogenase, and alcohol dehydrogenase were all decreased in response to caloric restriction. Fructose 1-phosphate aldolase and creatine phosphokinase were not altered. Likewise, enzymes associated with lipid metabolism (malic enzyme and glycerokinase) were reduced (fatty acid synthetase was reduced, but not to a statistically significant degree). Activities of enzymes supporting gluconeogenesis (glutamate oxaloacetate transaminase, tyrosine aminotransferase, glutamate pyruvate transaminase, glutamate dehydrogenase, amino acid oxidase, malate dehydrogenase, and glucose 6-phosphatase) were either unchanged or increased significantly by caloric restriction. Glucagon levels were decreased. Comparisons between young ad libitum fed and older calorically restricted rats revealed similar but not identical metabolic activity. These results suggest that caloric restriction produces an effect on intermediary metabolism, favoring the role of glucagon and glucose synthesis; but limiting the role of insulin and glucose catabolism in the liver. The former observation provides for the efficient support of peripheral tissues and the latter a level of energy production necessary only for self maintenance. Limited lipid metabolism suggests decreased potential for fatty acid epoxide formation and free radical damage to cellular macromolecules. Additionally, caloric restriction may delay the progressive age associated changes in the activities of some of the enzymes investigated.
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PMID:Effect of chronic caloric restriction on hepatic enzymes of intermediary metabolism in the male Fischer 344 rat. 266 33

The early stages of insulin-dependent diabetes mellitus are characterized by a selective inability to secrete insulin in response to glucose, coupled to a better response to nonnutrient secretagogues. The deficient glucose response may be a result of the autoimmune process directed toward the beta-cells. Interleukin-1 (IL-1) has been suggested to be one possible mediator of immunological damage of the beta-cells. In the present study we characterized the sensitivity of beta-cells to different secretagogues after human recombinant IL-1 beta (rIL-1 beta) exposure. Furthermore, experiments were performed to clarify the biochemical mechanisms behind the defective insulin response observed in these islets. Rat pancreatic islets were isolated and kept in tissue culture (medium RPMI-1640 plus 10% calf serum) for 5 days. The islets were subsequently exposed to 60 pM human recombinant IL-1 beta during 48 h in the same culture conditions as above and examined immediately after IL-1 exposure. The rIL-1 beta-treated islets showed a marked reduction of glucose-stimulated insulin release. Stimulation with arginine plus different glucose concentrations, and leucine plus glutamine partially counteracted the rIL-1 beta-induced reduction of insulin release. The activities of the glycolytic enzymes hexokinase, glucokinase, and glyceraldehyde 3-phosphate dehydrogenase, were similar in control and IL-1-exposed islets. Treatment with IL-1 also did not impair the activities of NADH+- and NADPH+-dependent glutamate dehydrogenase, glutamate-aspartate transaminase, glutamate-alanine transaminase, citrate synthase, and NAD+-linked isocitrate dehydrogenase. The oxidation of D-[6-14C]glucose and L-[U-14C]leucine were decreased by 50% in IL-1-treated islets. Furthermore, there was a significant decrease in the ratios of [2-14C]pyruvate oxidation/[1-14C]pyruvate decarboxylation and L-[U-14C]leucine oxidation/L-[1-14C]leucine decarboxylation, indicating that IL-1 decreases the proportion of generated acetyl-coenzyme-A residues undergoing oxidation. However, in the presence of IL-1 there was a significant increase in L-[U-14C]glutamate oxidation. These combined observations suggest that exposure to IL-1 induces a preferential decrease in glucose-mediated insulin release and mitochondrial glucose metabolism. This mitochondrial dysfunction seems to reflect an impairment in proximal steps of the Krebs cycle. It is conceivable that the IL-1-induced suppression and shift in islet metabolism can be an explanation for the beta-cell insensitivity to glucose observed in the early phases of human and experimental insulin-dependent diabetes mellitus.
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PMID:Differential sensitivity to beta-cell secretagogues in cultured rat pancreatic islets exposed to human interleukin-1 beta. 266 6

The injection of sodium nitroprusside (SNP) into mice induced a hyperglycemic response which was reduced by pretreatment with acetylsalicylate (ASA). The activity of glutamate dehydrogenase was significantly increased in islets from pancreases removed after SNP injection. This effect was prevented by pretreatment with ASA. Isolated mouse islets incubated with SNP exhibited stimulated activity of glutamate dehydrogenase both in the presence of low and high glucose concentrations, whereas the release of insulin was stimulated at low but inhibited at high glucose concentrations. These changes were abolished in the additional presence of ASA. The findings indicate that the hyperglycemic action of SNP may be related to changes in the generation of cyclooxygenase products.
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PMID:Inhibition by acetylsalicylate of the hyperglycemic response induced in mice by sodium nitroprusside. 269 44

The hybridoma, 62H3, which secretes a monoclonal IgG2b with anti-HLA-DR specificity, was expanded in pristane-primed BALB/c mice and the antibody was isolated from the ascitic fluid by affinity chromatography on Protein A-Sepharose. The purified IgG2b antibody was tested by an enzyme immunoassay for antibody activity against a panel of 40 self and non-self antigens. It was found to react strongly with beta-galactosidase, actin, glutamate dehydrogenase, rabbit and human IgG and di- and trinitrophenyl groups; and moderately with tubulin, insulin and phosphorylcholine; but it did not react with various other self and non-self antigens, such as DNA, albumin, keyhole limpet hemocyanin, hen lysozyme and horseradish peroxidase. Fab and Fc fragments were prepared from this IgG2b by papain proteolysis. The Fab fragment possessed the same spectrum of polyreactivities as the native IgG2b, whereas no activity was detected with the Fc fraction. In order to investigate the properties of the antigen binding site, the actin, TNP and rabbit IgG antibody activities were studied in more detail by enzyme immunoassay, Western blot and immunocytochemistry. The monomolecular nature of this multireactivity was confirmed by immunoabsorption analysis. Furthermore, 62H3 monoclonality was also verified by comparative isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis with other monospecific antibodies. The dissociation constants (Kd) of antigen-antibody equilibria in solution were measured. The Kd for actin was 1.11 +/- 0.24 x 10(-5) M and the Kd for TNP-BSA was 8.7 +/- 0.51 x 10(-7) M. No interaction with rabbit IgG could be detected in solution. These findings raise the question of the possible implication in autoimmune pathology or in normal physiology of IgG class polyspecific antibodies with solid-phase restricted cross-reactive rheumatoid factor activity.
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PMID:Immunochemical studies of a murine polyreactive IgG2b autoantibody with rheumatoid factor activity. 277 Jul 48

High aminotransferase activities catalyzing the reactions between L-glutamate and L-glutamine and the aliphatic ketomonocarboxylic acids 2-ketoisocaproate, 2-ketocaproate, and 2-ketoisovalerate were observed in pancreatic B-cell mitochondria. While maximal rates of transamination with L-glutamate were observed in the presence of micromolar concentrations of keto acid, maximal rates of transamination with L-glutamine were recorded only in the presence of millimolar concentrations of keto acid. The insulin secretagogue 2-ketoisocaproate was the most effective transamination partner for L-glutamate, while the insulin secretagogue 2-ketocaproate was the most effective transamination partner for L-glutamine. Since B-cell mitochondria are well supplied with L-glutamate and L-glutamine, 2-ketoglutarate generation in the presence of these two neutral 2-keto acids may be an important prerequisite for their insulin secretory potency. High rates of transamination of 2-ketoglutarate were observed in the pancreatic B-cell mitochondria with the branched-chain amino acids L-leucine and L-valine, but not with L-norleucine. In connection with the ability of L-leucine to activate glutamate dehydrogenase, this high activity of the branched-chain amino acid aminotransferase in pancreatic B-cell mitochondria may provide an explanation for the insulin secretory potency of this amino acid.
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PMID:Transamination of neutral amino acids and 2-keto acids in pancreatic B-cell mitochondria. 286 44

The effect of physiological concentrations of insulin (2 and 20 ng/ml) on glutamine synthetase (GS) and glutamate dehydrogenase (GDH) activities were compared in mouse and chick glial cells in culture. Addition of insulin to serum-containing medium increased the level of GS and GDH activities in glial cells prepared from 14-15-day-old embryonic mice. A similar but less pronounced effect was observed with glia derived from newborn mouse brain. In absence of serum, addition of insulin had no effect on the tested enzymes. The effects of insulin on enzymatic activities of glial cells from 14-15-day-old embryonic chick brain hemispheres were, in contrast, quite different. A significant decrease of GS activity was induced by the hormone, only in the absence of serum. Conversely, the presence of serum enhanced an inhibitory effect of insulin toward chick GDH. The different effects of insulin and the different serum dependence observed for the mammalian and the avian model could reflect fundamental chemical differences between both species as indicated by immunoelectrophoretic analysis. However, it can be concluded that insulin may be a physiological factor regulating glial maturation and amino acid neurotransmitter metabolism in the central nervous system.
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PMID:Differential modulation of glutamate metabolizing enzymes in mouse and chick cultured glial cells by insulin. 290 31

This study provides explanation for conflicting evidence in the literature relating to changes in mitochondrial function and metabolic parameters during chemically induced diabetes. Diabetes of 3 days' duration (early ketosis) did not alter heart, kidney, or liver mitochondrial respiratory rates with glutamate or succinate even though serum glucose and triglycerides were elevated. Diabetes of 5 weeks' duration did not alter kidney or liver mitochondrial function in the fed adult rat although weight gain was depressed. The amount of kidney mitochondrial protein isolated per gram of tissue was increased by 30% in the diabetic. This increase was reversed by insulin treatment as were the other biochemical modalities measured. Superimposition of a 24-hr fast resulted in enhanced gluconeogenesis as measured by an animal weight loss of 17% within 24 hr (liver weight loss, 21%) and an elevation of serum urea nitrogen by 180% compared to fasted control. Respiratory rates of diabetic kidney mitochondria with glutamate were unaffected in the fasted animal whereas diabetic liver mitochondrial respiratory rates during succinate oxidation were reduced by 43%. Respiratory control was unchanged in the fasted diabetic rat. All the observed changes were reversed by insulin. Variation in the serum and liver metabolic indices (urea nitrogen, creatinine, glycerol, free fatty acids, free amino acids, triglycerides, and glucose) and liver mitochondrial responses to 7 weeks of chemically induced diabetes was affected by the rat strain, Sprague-Dawley versus Sherman, and rat weight, 72 g versus 222 g. Liver mitochondrial respirations in fed Sherman rats were not depressed by diabetes. Both rat strains had elevated liver free fatty acids and glutamate dehydrogenase activity in the diabetic state. Serum leucine, isoleucine, and valine were more elevated and serum lysine and arginine were more depressed in the diabetic Sprague-Dawley rat than in the Sherman rat. Conjectures on these results are presented in the text.
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PMID:Metabolic and mitochondrial disturbances in streptozotocin-treated Sprague-Dawley and Sherman rats. 293 62

We recently described a preferential reduction of the secretory response to nutrient secretagogues (glucose; leucine plus glutamine) in islets maintained in culture after in vitro exposure to streptozotocin (SZ). The present study is an attempt to further clarify the biochemical mechanisms behind this defective insulin response. Mouse pancreatic islets were collagenase isolated and, after 4-5 days in culture, exposed during 30 min at 37 C to 1.8 mM SZ or vehicle alone (controls). The islets were subsequently cultured for 7 days in medium RPMI 1640 plus 10% calf serum, before the enzymatic and metabolic studies were performed. The activities of the glycolytic enzymes, hexokinase, glucokinase, and glyceraldehyde 3-phosphate dehydrogenase, were similar in the control and SZ-exposed islets. The relative amount of cytosolic and mitochondria-bound hexokinase was also unaffected by SZ. However, there was a 30-40% decrease in the activity of NAD+- and NADP+-dependent glutamate dehydrogenase and glutamate-aspartate transaminase in the SZ-treated islets. This coincided with a 40% decrease in L-[U-14C]glutamine oxidation in the SZ-treated islets. The D-glucose catabolism was further examined in the presence of D-[5-3H] and D-[6-14C] glucose. There was no difference between control and SZ islets in terms of glucose utilization at either 1.7 or 16.7 mM glucose. The oxidation of D-[6-14C]glucose was nevertheless decreased by more than 50% in SZ islets incubated at 16.7 mM (but not 1.7 mM) glucose. Altogether, these converging observations suggest a perturbation of distal regulatory processes, apparently at the mitochondrial level, in the D-glucose and L-glutamine catabolism of SZ-exposed islets. Whether this reflects a primary action of SZ on the islet mitochondria, or an inhibitory effect of SZ on the synthesis of mitochondrial enzymes, as a result of nuclear DNA damage, remains to be elucidated.
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PMID:Defective catabolism of D-glucose and L-glutamine in mouse pancreatic islets maintained in culture after streptozotocin exposure. 296 23

An atypical creatine kinase (CK) isoenzyme migrating cathodically to CK-MM in the electrophoresis was observed as response to the embolization of the right hepatic artery in two patients with liver metastasis. The time course of the atypical CK release was compared to that of tumor secretion products, i.e., insulin and 5-hydroxy-in-dol-acetic acid. The CK isoenzyme probably reflects a mitochondrial breakdown of the metastasis in question. The influence of the treatment on liver function was characterized by a marginal augmentation of ASAT and ALAT and by a small but significant leakage of mitochondrial glutamate dehydrogenase. In addition to the atypical CK, CK-BB, and CK-MB isoenzymes were found in the serum of the patient with primary carcinoid carcinoma.
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PMID:Creatine kinase isoenzymes: biochemical findings after therapeutical embolization of the hepatic artery in two patients with liver metastasis of an islet cell carcinoma or a carcinoid tumor. 298 64

Rat pancreatic endocrine tumours were induced by administration of streptozotocin plus nicotinamide. Fifteen to eighteen months later tumours with wet weights of 0.1 to 224 mg were isolated. These tumours were compared with normal rat pancreatic islets. Insulin release from perifused tumours was stimulated by D-glucose, L-leucine, 2-ketoisocaproate, and D-glyceraldehyde, potentiated by theophylline and inhibited by norepinephrine. Compared with isolated rat pancreatic islets, however, insulin secretory responsiveness to glucose stimulation and insulin content were reduced in tumour tissue. Hypoglycaemia in tumour bearing rats and impaired diffusion of insulin out of the tumours may explain this difference. The pattern of enzyme activities observed in tumour tissue was typical for pancreatic endocrine tissue. The activities of succinate dehydrogenase, the two types of the monoamine oxidase, and alpha-glucosidase were in the normal range in tumour tissue. Only the activities of 5'nucleotidase and glutamate dehydrogenase were decreased. Immunocytochemical analysis of the tumours revealed that they contained an average of 91% B-cells. In addition 8% of D-cells were encountered. Proportions of A-cells and PP-cells ranged below 1%. Thus this endocrine tumour of the pancreas with a high proportion of functionally intact B-cells is an interesting model for studying regulation of secretion and endocrine tumour development.
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PMID:Secretory, enzymatic, and morphological characterization of rat pancreatic endocrine tumours induced by streptozotocin and nicotinamide. 299 5


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