Theoretical Analysis of the Built-in Metabolic Pathway Effect on the Metabolism of Erythrocyte-Bioreactors That Neutralize Ammonium

The limitations of the efficiency of ammonium-neutralizing erythrocyte-bioreactors based on glutamate dehydrogenase and alanine aminotransferase reactions were analyzed using a mathematical model. At low pyruvate concentrations in the external medium (below about 0.3 mM), the main limiting factor is the rate of pyruvate influx into the erythrocyte from the outside, and at higher concentrations, it is the disappearance of a steady state in glycolysis if the rate of ammonium processing is higher than the critical value (about 12 mM/h). This rate corresponds to different values of glutamate dehydrogenase activity at different concentrations of pyruvate in plasma. Oxidation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) by glutamate dehydrogenase decreases the fraction of NADPH in the constant pool of nicotinamide adenine dinucleotide phosphates (NADP + NADPH). This, in turn, activates the pentose phosphate pathway, where NADP reduces to NADPH. Due to the increase in flux through the pentose phosphate pathway, stabilization of the ATP concentration becomes impossible; its value increases until almost the entire pool of adenylates transforms into the ATP form. As the pool of adenylates is constant, the ADP concentration decreases dramatically. This slows the pyruvate kinase reaction, leading to the disappearance of the steady state in glycolysis.

Evaluation of Glutamate Dehydrogenase Activity and Insulin Secretion in Mice Exposed to Dexamethasone

Background and Aims: Diabetes is one of the most important endocrine disrupters and is associated with various hormones, including those that can lead to diabetes. Glucocorticoid use may lead to insulin resistance. Dexamethasone is one of these glucocorticoid compounds. Glutamate dehydrogenase plays a key role in the production of glutamate in the secretion of insulin. Based on these hormonal interactions, the aim of this study was to determine the activity of glutamate dehydrogenase and insulin secretion in dexamethasone-exposed mice. Materials and Methods: Twenty eight mice were divided into 4 experimental groups. Group 1 received standard normal saline as a control. Group 2 received standard food and received 1 mg / kg dexamethasone per day. Group 3 received standard diet and dexamethasone 3 mg / kg / day and group 4 with standard diet 5 mg / kg dexamethasone per day. After 21 days, the animals were killed, the pancreas and glutamate dehydrogenase, insulin, and serum glucose levels were determined. Results: Dexamethasone increased serum glucose levels significantly (P <0.05). Dexamethasone increased the glutamate dehydrogenase activity and insulin levels in dexamethasone treated mice (p<0.05) Conclusions: These results suggestd that dexamethasone increases glucose which leads to elevating glutamate dehydrogenase activity, and then increasing insulin. However, insulin was not enough to normalize glucose levels and led to hyperglycemia. Therefore, it is suggested to reduce dexamethasone administration.

Platelet glutamate dehydrogenase activity and efficacy of antipsychotic therapy in patients with schizophrenia

Summary Background Evaluation of possible relationship between platelet glutamate dehydrogenase (GDH) activity and mental state of schizophrenia patients after antipsychotic pharmacotherapy. Methods Patients (n = 50) with chronic paranoid schizophrenia (F20.0) initially in acute psychotic state were examined before and after a treatment course with antipsychotics. When assessing the patients’ states using PANSS, the »responder« category was attributed to those patients who had not less than 30% reduction in the score for the corresponding PANSS »subscale«. The control group (n = 48) was age- and gender-matched with the patient group. Platelet glutamate dehydrogenase (GDH) activity was measured in patients twice, before and after the treatment course, and once in controls. Results Significantly reduced GDH activity was found in patients compared with controls. The patient group was divided into two subgroups according to median GDH activity at baseline: above and below the median GDH, subgroup 1 and subgroup 2, respectively. GDH activity significantly increased from its level at baseline after antipsychotic treatment in subgroup 2. Distribution of non-responders / responders to antipsychotic treatment (by PANSS scores) was significantly uneven among subgroups 1 and 2. In subgroup 1, GDH activity levels significantly correlated with PANSS scores after the treatment course. Conclusions Baseline platelet GDH activity might serve as a predictor of antipsychotic therapy efficacy in schizophrenia patients.