Possible Interaction: Glutathione and Glutamic Acid

“Department of Pharmacology, Setsunan University, Hirakata, Osaka 573-01, and *Kinshukai School …, Osaka 558 Reduced (GSH) as well as oxidized (GSSG) forms of glutathione exhibited concentration-… of radiolabeled L-glutamic acid (Glu) in synaptic membrane preparations obtained from rat brain … that occurred in vivo (10 7-10-3 M).”

“Further, L-GA elevated glutathione levels and attenuated nitric oxide levels, but failed to restore ATP levels 72 h after ischemia-reperfusion.”

“ Glu increases intracellular reactive oxygen species (ROS) production and induces mitochondrial dysfunction as well as decreasing antioxidant defenses such as glutathione (GSH) and glutathione peroxidase activity.”

“Supplementation with both cystine and glutamic acid increases the synthesis of glutathione (GSH), which has a marked effect on immune cell function, as compared with supplementation with either amino acid alone in human macrophages in vitro.”

“The coupling of the glutathione adduct and the products from the mercapturic acid pathway with the glutamic acid led to unusual peptide conjugates.”

“…:Glutathione , both reduced (GSH) … binding of l‐[3H]‐glutamic acid (l‐[3H]Glu) and dl‐(E)‐2‐[3H]amino‐4‐propyl‐5‐phosphono‐3‐pentenoic acid ([3H]CGP‐39653) in … potent displacement of binding of dl‐α‐amino‐3‐hydroxy‐5‐[3H]‐methylisoxazole‐4‐propionic and [3H]kainic acids.”

“Antioxidants also prevented the delayed cell death caused by lowering the concentration of cystine in the medium to 5 microM. Incubation of the cells with 10 mM Glu caused a marked decrease in cellular GSH levels.”

“In contrast, the toxicity was suppressed by increasing the cystine concentration to 500 to 1000 microM. Reducing agents, cysteine (30-1000 microM), dithiothreitol (10-250 microM) and glutathione (GSH, 10-1000 microM) also protected the cells against the cytotoxicity of 10 mM Glu in a concentration-dependent manner.”

“Thus increases in glutamic acid uptake parallel increases in cellular glutathione, and glutamic acid may be a regulating factor in the increase in glutathione after exposure to hyperoxia.”

“Reduced as well as oxidized forms of glutathione exhibited a significant displacement of the specific binding of [3H]L-glutamic acid (Glu), a potential candidate for the central excitatory neurotransmitter, to the rat brain synaptic membranes.”

“Since the inhibitory effects of Cys on both the decrease in the ratio of GSH/GSSG and the induction of … inhibitors of gamma-glutamyl transpeptidase and gamma-glutamylcysteine synthetase, it is suggested that some of the inhibitory effects of Glu , Cys and Gly on … metabolism of the tripeptide GSH, ….”