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)

The effect of chloroquine on gluconeogenesis in isolated hepatocytes and kidney-cortex tubules of rabbit has been studied. The inhibitory action of 200 microM chloroquine was the highest in hepatocytes and renal tubules incubated with glutamine and glutamate+glycerol+octanoate, respectively, while in the presence of other substrates the drug action was less pronounced. With amino acids as substrates, the inhibition of gluconeogenesis was accompanied by a decreased glutamine production, resulting from a decline of glutamate dehydrogenase activity. A decrease in the urea production by hepatocytes incubated with chloroquine in the presence of glutamine but not NH4Cl as the source of ammonium is in agreement with this suggestion. The degree of inhibition by chloroquine of the rate of gluconeogenesis in renal tubules isolated from control rabbits was similar to that determined in diabetic animals. Chloroquine-induced changes in levels of intracellular gluconeogenic intermediates indicate a decrease in phosphoenolpyruvate carboxykinase and glucose-6-phosphatase activities probably due to increased concentration of 2-oxoglutarate, an inhibitor of these two enzymes. In view of the data, it is likely that inhibition by chloroquine of glucose formation in liver and kidney may contribute to the hypoglycaemic action of this drug. The importance of the inhibitory effect of chloroquine on glutamate dehydrogenase activity in the antihyperglycaemic action of the drug is discussed.
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PMID:The inhibition of gluconeogenesis by chloroquine contributes to its hypoglycaemic action. 1168 98

Human glutamate dehydrogenase exists in hGDH1 (housekeeping isozyme) and in hGDH2 (nerve-specific isozyme), which differ markedly in their allosteric regulation. In the nervous system, GDH is enriched in astrocytes and is important for recycling glutamate, a major excitatory neurotransmitter during neurotransmission. Chloroquine has been known to be a potent inhibitor of house-keeping GDH1 in permeabilized liver and kidney-cortex of rabbit. However, the effects of chloroquine on nerve-specific GDH2 have not been reported yet. In the present study, we have investigated the effects of chloroquine on hGDH2 at various conditions and showed that chloroquine could inhibit the activity of hGDH2 at dose-dependent manner. Studies of the chloroquine inhibition on enzyme activity revealed that hGDH2 was relatively less sensitive to chloroquine inhibition than house-keeping hGDH1. Incubation of hGDH2 was uncompetitive with respect of NADH and non-competitive with respect of 2-oxoglutarate. The inhibitory effect of chloroquine on hGDH2 was abolished, although in part, by the presence of ADP and L-leucine, whereas GTP did not change the sensitivity to chloroquine inhibition. Our results show a possibility that chloroquine may be used in regulating GDH activity and subsequently glutamate concentration in the central nervous system.
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PMID:Inhibitory properties of nerve-specific human glutamate dehydrogenase isozyme by chloroquine. 1804 6