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C R Murthy

Publications and source records attributed to C R Murthy.

44 records · Page 3Linked to original sources
PubMed1983

Effects of methionine sulfoximine on the enzymes of glutamate metabolism in isolated astrocytes of rat brain.

The enzymes of glutamate metabolism were estimated in astrocytes isolated from brains of normal rats and those injected with the potent convulsant, methionine sulfoximine (MSO), which inhibits glutamine synthetase and induces Alzheimer type II astrocytosis. The wet weight, dry weight; contents of DNA, RNA, protein and the activities of glutamate dehydrogenase and aspartate aminotransferase were elevated following MSO administration. The metabolic effects of MSO were found to be different from those of ammonia wherein a fall in the activity of glutamate dehydrogenase and an increase in the activity of glutamine synthetase was noticed. Based on these results it is suggested that there might be an inverse relationship in the functioning of these two enzymes. Such a relationship would help in preventing the depletion of energy pools in a given cellular compartment during ammonia detoxification.

Alanine Transaminase↗
PubMed1983

Studies on acetylcholinesterase and gamma-glutamyltranspeptidase in mouse brain in ammonia toxicity.

Short- and long-term ammonia toxicity was induced in mice by intraperitoneal injection, respectively, of single and six doses of 0.6 mM ammonium acetate per 100 g of body weight. The animals were sacrificed half an hour after either the single injection or after the last injection of six doses. Under these experimental conditions the ammonia levels were found to be elevated twofold in cerebral cortex, brain stem, and basal ganglia after the administration of a single dose of ammonium acetate. A fourfold increase in the content of ammonia was observed in cerebral cortex, brain stem, and basal ganglia after six injections. An elevation in the activity of pseudocholinesterase (enzyme localized in brain capillaries and glial cells) in all the above four regions resulted as a short-term effect of ammonia toxicity. True acetylcholinesterase was found to be elevated in all the four regions in short-term and in long-term ammonia toxicity. Gamma-glutamyltranspeptidase (GGTP), another enzyme localized in cerebral capillaries and glial cells, was found to be depressed in all the regions of the brain in both short- and long-term ammonia toxicity. The implications of these results are discussed in relation to glial cell function.

Acetylcholinesterase↗
PubMed1983

Calcium-dependent release of acetyl-coenzyme A from liver mitochondria.

Calcium ions (10 microM) enhance the permeability of the hepatic inner mitochondrial membrane to acetyl-CoA (and CoA). This effect is suppressed by the absence of phosphate ions or by the presence of EGTA, La3+, or ruthenium red. Exposure of mitochondria to Ca2+ for short intervals of time (e.g., 10 min) results in a reversible permeability change with release of acetyl-CoA and retention of sensitivity to EGTA. It is suggested that conditions resulting in an increase of the calcium ion concentration in the cytoplasm may thereby increase the rate of transfer of acetyl-CoA from the mitochondria to the cytoplasm.

Acetyl Coenzyme A↗
PubMed1980

Studies on AMP deaminase and 5'-nucleotidase in rat brain under different experimental conditions.

Adenosine monophosphate (AMP) deaminase and 5'-nucleotidase, the two enzymes involved in the disposal of AMP, have been detected in different regions of normal rat brain and in animals subjected to heightened neuronal activity (leptazol-induced convulsions) and to depression of the central nervous system (CNS) by the administration of barbiturates. They have also been estimated in the CNS of animals subjected to anoxia or treated with lithium and ammonium salts. The AMP deaminase activity was found to be highest in cerebellum and lowest in cerebral cortex, while the 5'-nucleotidase activity was found to be highest in brain stem and lowest in cerebellum. The AMP deaminase activity was elevated in all the regions of brain during the preconvulsive and convulsive periods. The activity returned to normal during recovery. The activity of 5'-nucleotidase was found to be depressed in the preconvulsive and post-convulsive periods. The enzyme was also found to be depressed in all the three regions after the administration of barbiturates. Administration of lithium or ammonium salts of induction of anoxic states resulted in an increase in the activity of AMP deaminase in all the three regions of brain. These results are discussed in relation to the probable production of cyclic AMP and cyclic guanosine monophosphate (GMP) which may have depressive and excitatory roles, respectively, in brain. It appears that increased AMP deaminase activity is associated with increased neuronal activity while depression of 5'-nucleotidase activity is associated with conditions of decreased CNS excitability.

AMP Deaminase↗
PubMedDate not supplied

Some metabolic effects of ammonia on astrocytes and neurons in primary cultures.

Some metabolic effects on primary cultures of neurons or astrocytes were studied following acute or chronic exposure to pathophysiological concentrations (usually 3 mM) of ammonia. Three parameters were investigated: (1) 14CO2 production from 14C-labeled substrates [glucose, pyruvate, branched-chain amino acids (leucine, valine, isoleucine), and glutamate]; (2) interconversion between glutamate and glutamine; and (3) incorporation of label from labeled branched-chain amino acids into proteins. Neither acute nor chronic exposure to ammonia had any effect on 14CO2 production from [U-14C]glucose in astrocytes and neurons, whereas under certain conditions 14CO2 production from [1-14C]pyruvate in astrocytes was inhibited by ammonia. Production of 14CO2 from [1-14C]branched-chain amino acids was inhibited by acute, but stimulated by chronic, exposure to ammonia (3 mM) in astrocytes, with less effect in neurons. Production of 14CO2 from [1-14C]glutamate in both astrocytes and neurons was inhibited by acute exposure to ammonia. In astrocytes, glutamate levels tended to decrease and glutamine levels tended to increase following acute exposure to ammonia; in neurons, both glutamine and glutamate levels decreased. Protein content (per culture dish) increased in astrocytes but not in neurons, after chronic exposure to ammonia, possibly as a result of enhanced protein synthesis and/or by inhibition of protein degradation.

Amino Acids↗
PubMedDate not supplied

Elevation of glutathione levels by ammonium ions in primary cultures of rat astrocytes.

It is well established that ammonia is detoxified in the brain to form glutamine and that astrocytes play a major role in this process. The synthesis of glutamine requires glutamate and ATP. Since glutamate and ATP are also required for the synthesis of glutathione (GSH), we examined the effect of pathophysiological concentrations of ammonia on levels of GSH in primary cultures of astrocytes. GSH content in the medium increased in a dose- and time-dependent manner in the presence of ammonia. After an initial decrease, cellular GSH content increased in a similar manner. The levels of glutathione disulfide (GSSG) were also increased. A linear relationship was observed between ammonia concentration and the increase in GSH levels. An increase in the efflux of GSH from cells into medium was also observed under these conditions. Buthionine sulfoximine and acivicin, but not methionine sulfoximine, blocked the ammonia induced increase in GSH levels. No, or minor, changes in the activities of enzymes (gamma-glutamyl transpeptidase, GSH reductase and GSH-peroxidase) that might influence GSH levels were identified and thus could not account for the ammonia induced increase in GSH levels in astrocytes. These findings indicate that pathophysiological concentrations of ammonium ions result in increased astroglial levels of GSH which may affect the metabolism and function of astrocytes.

Ammonia↗