Glutamylcysteine synthetase

Li S, Thompson SA, Woods JS. 1996. Localization of gamma-glutamylcysteine synthetase mRNA expression in mouse brain following methyhnercury treatment using reverse transcription in situ PCR amplification. Toxicol Appl Pharmacol 140 180-187. 

G5. Gipp, J. J., Chang, C., and Mulcahy, R. T Cloning and nucleotide sequence of a full length cDNA for human liver -y-glutamylcysteine synthetase. Biochem Biophys. Res. Commun. 185, 29-35 (1992). 

The cycle is renewed after the cysteine formed in reaction 6 and the glutamate derived from reaction 6 are converted to y-glutamylcysteine via y-glutamylcysteine synthetase (reaction 1). 

Patients have metabolic acidosis caused by excessive formation of 5-oxoproline (pyroglutamic acid Fig. 40-6, reaction 2). This occurs because the diminution of intracellular glutathione relieves the feedback inhibition on the y-glutamylcysteine synthetase pathway (reaction 1), thereby augmenting the concentration of y-glutamylcys-teine and the subsequent conversion of this dipeptide to cysteine and 5-oxoproline in the cyclotransferase pathway (reaction 4). 

Arsenate reductase (and y-glutamylcysteine synthetase) Increased for arsenate, Cd Increased for arsenic, Cd ... 

Gullner, G., Komives, T., and Rennenberg, H., 2001, Enhanced tolerance of transgenic poplar plants overexpressing y-glutamylcysteine synthetase towards chloroacetanilide herbicides, / Exp. Bot. 52 971-979. 

Zhu, Y. L., Pilon-Smits, E. A. H., Tarun, A. S., Weber, S. U., Jouanin, L., and Terry, N., 1999b, Cadmium tolerance and accumulation in Indian mustard is enhanced by overexpressing y-glutamylcysteine synthetase. Plant Physiol. 121 1169-1177. 

ADP NADH Disappearance Pyruvate Kinase and Lactate Dehydrogenase Fructokinase, y-Glutamylcysteine Synthetase, Mannokinase, ATPase ... 

A three-substrate, three-product enzyme-catalyzed reaction scheme in which one particular substrate (A) is the only substrate that can bind to the free enzyme. After the EA binary complex has formed, the other two substrates (B and C) can bind in any order. Following the catalytic event, two of the products (P and Q) can be released in a random sequence, but the third product (R) has to be the last product released. Citrate cleavage enzyme and y-glutamylcysteine synthetase are reported to operate by this mechanism. See Multisubstrate Mechanisms... 

Ishikawa T, Bao J, Yamane Y, Akim am K, Frindrich K, Wright CD, et al. Coordinated induction of MRP/GS-X pump and gamma-glutamylcysteine synthetase by heavy metals in human leukemia cells. J Biol Chem 19967 271 14,981-14,988. 

Myhrstad, M.C.W. et ah, Flavonoids increase the intracellular glutathione level by transactivation of the y-glutamylcysteine synthetase catalytical subunit promoter. Free Radical Biol. Med., 32, 386, 2002. 

We have further investigated the dependency of HC "NO synthesis on cellular GSH levels and BH4 availability. Inhibition of GSH synthesis using the 7-glutamylcysteine synthetase inhibitor buthionine sulfoximine, which blocks de novo GSH synthesis, markedly reduced GSH levels in cultured HC, approximately 5% of control, but resulted in only a 40-50% reduction in NO2 biosynthesis in response to cytokines and LPS. More effective was the inhibition of GSH reductase with l,3-bis(chloroethyl)-l-nitrosurea, which prevents the recycling of GSSH back to GSH. GSH levels also fell in these cells, but a marked decrease in NO2" formation was seen, suggesting that GSH recycling was an important aspect of -NO formation. Similar results had been reported for con-... 

Purified preparations of y-glutamylcysteine synthetase can also catalyze the formation of pyrrolidone carboxylic acid (llla,b). This enzyme catalyzes the synthesis of y-glutamylcysteine according to the following reaction ... 

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