Y-glutamylcysteine synthetase

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... 

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. 

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 ... 

Fig. 1. The y-glutamyl cycle. I, y-Glutamylcysteine synthetase II, glutathione synthetase III, y-glutamyl transpeptidase IV, y-glutamyl cyclotransferase V. peptidase. PCA = pyrrolidone carboxylic acid AA = amino acid.

As noted above, the X-ray sensitization of cells using MGd has been investigated extensively and appears to operate at least in part in an oxygen dependent manner, with cytotoxic activity that is substantially enhanced upon the addition of ascorbate to the media [69], The cytotoxic activity of MGd can also be enhanced with L-buthionine-S,R-sulfoximine (BSO), an irreversible inhibitor of an enzyme involved in glutathione biosynthesis (y-glutamylcysteine synthetase), that serves to suppress the synthesis of ROS-protective glutathione. Presumably, this activity is responsible for the in vitro radiation enhancing effect of BSO [66,71],... 

Figure 13.5. y-Glutamylcysteine synthetase (y-GCS), a rate-limiting and key enzyme in glutathione synthesis. 

Through the action of y-glutamylcysteine synthetase (GLC) and glutathione synthetase (GS), GSH can be synthesized in the cytosol of most mammalian cells. 

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