GSH addition

Cleavage of the carbon backbone is reported to be mediated by hydrolases [63]. However, there are no indications that this side-reaction proceeds enzymatically. Instead formation of retro-Claisen products 12 and 13 proceeds via GSH addition to the carbonyl center in 2. The active role of GSH was demonstrated with GSH-depleted cells. After treatment with N-ethyl maleimide (NEM) [64] no retro-Claisen product was detectable. The same applied for NEM-treated cell liquor. 

GSH addition potentiates the action of adrenaline in relaxing smooth muscle (144). Under similar conditions cysteine is slightly less effective, whereas ascorbic acid is only one-ninth as effective (144). GSH, at a concentration of 25 mg. %, inhibits the in vitro oxidation of adrenaline (145, 144). Although ascorbic acid has a similar effect, on a molar basis, GSH was more than four times more effective (144). The potentiating effects of GSH have been attributed to this protection of adrenaline against oxidation (144). 

The methylation of As or MMA requires the presence of a normal intracellular (millimolar) concentration of GSH (Buchet and Lauwerys 1985). Methylation of arsenite or MMA did not occur in either rat or mouse liver or kidney homogenates without addition of GSH. Addition of GSH promoted both mono- and dimethylation in these homogenates. MMA... 

Recognition of the thio group s key role in biochemistry has led to studies of l,4-ben2oquinone with glutathione, a tripeptide 7-Glu-Cys-Gly (GSH). The cross-oxidation of the initial addition product by excess quinone leads, under physiological conditions, to all three isomeric products (46), ie, the 2,3-and 2,6-isomers as well as the 2,5-disubstituted l,4-ben2oquinone shown. 

DMPG, whereas combinations of DMPG with cysteine, glucan, GSH, or 5-hydtoxytryptamine are only additive (255). 

If the cardiac redox state (reflected by fluctuations in the ratio of GSH and GSSG) is important in the regulation of the function of some enzymes, the manipulation of this ratio may result in parallel changes in enzyme activity. Thus, a reduction of Na/K ATPase activity associated with the application of 1 mM GSSG has been shown to be reversed and completely overcome, in a concentration-dependent manner, by the subsequent addition of GSH (O.l-l.OmM) (Haddock et al., 1991) (see Fig. 4.10). 

Figure 4.9 Effect of reduced glutathione (GSH) (0.25-1.0 ihm) and oxidized glutathione (GSSG) (0.25-1.0 mM) on ouabain-sensitive Na/K ATPase activity. An isolated Na/K ATPase preparation was prepared from fresh bovine ventricular tissue. Na/K ATPase activity was determined and quantified by the ouabain-sensitive hydrolysis of ATP to yield Inorganic phosphate. The rate of inorganic phosphate production was compared prior to and following the addition of either GSH or GSSG to the Incubation mixture. The data are presented as...

The GSH reductase inhibitor l,3-bis(2-chloroethyl)-l-nitrosourea (BCNU) also promotes corneal swelling in the isolated cornea. The addition of GSH prevents the action of BCNU as the cornea needs a constant supply of NADPH for maintaining adequate concentrations of reduced glutathione for the detoxification of hydrogen peroxide. It has been shown that hydrogen peroxide and BCNU primarily affect the permeability of the endothelial cells rather than the active processes transporting sodium and chloride ions across the membrane (Riley, 1985). 

Necheles et al. (N4) first reported a genetically determined homozygous GSH-Px deficiency associated with neonatal jaundice and mild hemolysis. Spontaneous recovery from hemolysis was noted 3 months after birth. Thereafter, several cases with GSH-Px deficiency were reported. Newborn infants exhibit significantly lower red blood cell GSH-Px activity and serum selenium concentrations than adult control subjects, and a significantly positive correlation between selenium concentration and GSH-Px activity has been observed. Furthermore, the addition of selenium stimulates, both in vivo and in vitro, the GSH-Px activity. The neonatal red blood cell GSH-Px deficiency may be partially due to insufficient availability of selenium during pregnancy (P9). Therefore, the diagnosis of GSH-Px deficiency in newborn infants must be made carefully. 

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