Glutathione GSH synthetase

During the protein engineering of E. coll B glutathione synthetase (GSH) (22), we happened to find that a sequence segment of the amino acid sequence of GSH, from Arg-55 to Ile-96, Is similar to those of mammalian and bacterial dlhydrofolate reductases (DHFRs)... 

Table I. Local Amino Acid Sequence Similarities between E. coli B Glutathione Synthetase (GSH) and Other Enzymes...

Glutathione, which is synthesized by two ATP molecules requiring synthetase enzymes (y glutamate cysteine synthetase and glutathione synthetase), is present at a concentration of about 2 mM in a red cell. To be an effective redox buffer , the ratio of GSH to GSSG must be kept high. This is achieved by the reduction of GSH by NADPH and glutathione reductase ... 

GSH is synthesized by two enzymes, y-glutamyl cysteine is formed from cysteine and glutamate by y-glutamyl synthetase. GSH is formed from y-glutamyl cysteine and glycine by glutathione synthetase. Both enzymes are found in the brain (Figure 13.7). 

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

Glutathione synthetase (EC 6.3.2.3 GSH-S) mediates the second step in the synthesis of GSH, by the addition of glycine to the dipeptide y-glutamylcysteine. The protein is a homodiraer of 52kDa. ... 

Glutathione (8.20) y-glutamylcysteinylglycine, is biosynthesised in a stepwise manner from the A -terminus but not by the ribosomal route. Instead, each peptide bond is formed under the control of a specific enzyme, glutamyl-cysteine synthetase and glutathione synthetase, respectively, with ATP as a substrate to form an acyl phosphate as an unsymmetrical anhydride. Reduced glutathione (GSH) with a thiol... 

The first step is catalysed by y-glutamylcysteine synthetase (GCS) and is ratelimiting for GSH biosynthesis [ 14]. The second step is catalysed by glutathione synthetase. 

Equation (18), catalyzed by glutathione synthetase (E.C. 6.3.2.3), has been demonstrated in acetone powders of bean seedlings (Webster, 1953). Activity required Mg " ", and was stimulated by K+. The stoichiometry and the mechanism of this reaction have not been studied in plants. Studies with purified GSH synthetase from other systems indicate that the reaction proceeds through enzyme-bound y-glutamylcysteinyl phosphate (Meister, 1974). 

The major antioxidant molecule, glutathione (GSH), is a tripeptide that is generated within the cytosol via glutamate-cysteine ligase and glutathione synthetase (Valko et al. 2007). This molecule has several... 

The therapeutic efficacy of oral administration of seed powder of M. oleifera (500 mg/kg, orally, once daily) post arsenic exposure (100 ppm in drinking water for 4 months) in rats has been investigated (49). Animals exposed to arsenic(lll) shows a significant inhibition of 8-aminolevulinic acid dehydratase (ALAD) activity, decrease in reduced glutathione (GSH) level and an increase in reactive oxygen species (ROS) in blood. On the other hand, a significant decrease in hepatic ALAD, and an increase in 8-aminolevulinic acid synthetase (ALAS) activity is observed after arsenic exposure. These changes... 

Glutamylcysteine synthetase, cysteine, or methionine was 100 times more reactive to hypochlorous acid in comparison with amino acids that did not contain thiol groups (Folkes et al., 1995). Sublethal exposures to HOCl decreased GSH levels in several cell types (Vissers and Winterboum, 1995 Pullar et al., 1999). In a study by Pullar et al. (1999) using human umbilical vein endothelial cells, doses of 25 nmol of HOCl and less were sublethal when the exposure was done over 10 min, there was a concentration-dependent loss of intracellular GSH. Tissue exposure to HOCl resulted in a reduction of GSH. The metabolite of the HOCl interaction with GSH was an unexpected cyclic sulfonamide that was exported from the cell. The expected metabolites of glutathione disulfide (GSSH) and GSH sulfonic acid were actually minimal (Pullar et al., 2001). Inactivation of acetylcholinesterase by HOCl could be a contributory cause of airway hyperreactivity (den Hartog et al., 2002). 

It should be noted that L-BSO (buthionine sulfoximine) is a strong inhibitor against y-glutamylcysteine synthetase, the enzyme that catalyzes the first reaction of glutathione (GSH) biosynthesis. L-BSO has been accepted as an anticancer medicine. ... 

In addition to phase 1 and phase 2 enzymes, several other nonenzymatic and enzymatic proteins more or less involved in xenobiotic metabolism have been shown to be induced by OPZ these include y-glutamylcysteine synthetase (a rate-limiting enzyme involved in GSH synthesis), glutathione conjugate efflux pumps [50, 70], heme oxygenase 1, heavy... 

Figure 9. ArsC and y-ECS catalyzed reactions. The bacterial arsenate reductase (ArsC) catalyzes the electrochemical reduction of arsenate to arsenite. The bacterial y-glutamylcysteine synthetase (y-ECS) catalyzes the formation of y-glutamylcysteine (y-EC) from the amino acids glutamate and cysteine and is the committed step in the synthesis of glutathione (GSH) and phytochelatins, PCs (indicated by three arrows). Reduced arsenite can bind organic thiols (RS) such as those in y-EC, GSH, and PCs through the replacement of oxygen by organic sulfttr species.

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