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)

In a previous study we demonstrated thirteen amino acids to be essential and two to be partially essential for lymphocyte proliferation. Arginine is one of the essential amino acids, and the highly purified arginase strongly inhibited lymphocyte proliferation. The modulation of lymphocyte growth by various amino acid-degrading enzymes was studied. Peripheral lymphocytes were cultured in RPMI 1640 with or without amino acid-degrading enzyme for 72 h. A total of 17 commercial L-amino acid-degrading enzymes were studied. At 10 micrograms/ml, both lysine decarboxylase and asparaginase completely inhibited lymphocyte proliferation, arginase resulted in 78% inhibition and tyrosinase 57% inhibition. Other enzymes inhibited less than 20% lymphocyte proliferation; they included alanine dehydrogenase, arginine decarboxylase, aspartase, glutamic decarboxylase, glutamic dehydrogenase, glutaminase, histidase, histidine decarboxylase, leucine dehydrogenase, phenylalanine decarboxylase, phenylalanine hydroxylase, tryptophanase, and tyrosine decarboxylase. All four enzymes that strongly inhibited lymphocyte proliferation degraded amino acids that are essential for lymphocyte growth.
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PMID:Modulation of lymphocyte proliferation by enzymes that degrade amino acids. 212 55

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

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

Troglitazone is a peroxisome proliferator-activated receptor-gamma agonist that has been shown to halt mesangium expansion in experimental models of type 2 diabetes mellitus and to act directly on rat mesangial cells. Because glutamine serves as the precursor for cellular biosynthetic processes, we asked whether troglitazone would inhibit mesangial cell glutamine metabolism under these conditions. Confluent monolayers of rat mesangial cells were incubated in RPMI medium in the presence of troglitazone or vehicle (DMSO). Troglitazone effected a dose-dependent reduction in glutamine utilization and in alanine formation, associated with a decrease in monolayer collagen-glycosaminoglycan content. Despite the reduced glutamine uptake, ammonium formation did not decrease, consistent with increased glutamate flux through the deamination pathway. Assayable activity of the alanine aminotransferase decreased by 63%, whereas assayable glutamate dehydrogenase remained unchanged. In control monolayers, the sum of ammonium plus alanine plus glutamate nitrogen released accounted for <75% of the glutamine nitrogen uptake. In troglitazone-treated monolayers, all of the glutamine nitrogen taken up could be accounted for as ammonium nitrogen released into the medium. These results are consonant with troglitazone reducing glutamine metabolism and specifically the transamination pathway in rat mesangial cells associated with a reduction in collagen-glycosaminoglycan content.
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PMID:Troglitazone inhibits glutamine metabolism in rat mesangial cells. 1173 5