Cysteine glutathione synthesis

Williamson, J.M., Boettcher, B. and Meister, A. (1982). Intracellular cysteine delivery system that protects against toxicity by promoting glutathione synthesis. Proc. Natl Acad. Sci. USA 79, 6246-6249. 

This is followed by removal of the glutamic acid and the glycine residues, which is followed by acetylation of the remaining cysteine. Essential amino acids are required for the synthesis of the proteins involved, pantothenic acid for coenzyme A synthesis, and phosphorus for synthesis of the ATP needed for glutathione synthesis. Similar scenarios can be developed for glucuronide and sulfate formation, acetylation, and other phase II reaction systems. 

Studies indicated that cysteine supplementation is beneficial in restoring glutathione levels in children with severe edematous malnutrition (Badaloo et al., 2002). If the reduced rate of glutathione synthesis in kwashiorkor is convincingly attributed to a shortage of protein in the... 

Badaloo A, Reid M, Forrester T, et al. Cysteine supplementation improves the erythrocyte glutathione synthesis rate in children with severe edematous malnutrition. Am J Clin Nutr 76 646-652,2002. 

The hormonal regulation of GCS expression has special physiological relevance. Phenylephrine, glucagon or dibutyryl cAMP inhibit GCS activity, which decreases glutathione synthesis and leads to glutathione depletion in rat hepatocytes [26,27]. The loss of GCS activity induced by these stress hormones is mediated by phosphorylation of the catalytic GCS subunit due to activation of protein kinase A, protein kinase C or Ca -calmoduhn kinase [28]. Consequently, the stress response diminishes GSH synthesis, which may increase the availability of cysteine for the synthesis of stress proteins [14]. 

The rapid turnover of the soluble cysteine used for glutathione synthesis in... 

Chromophoric markers were afforded by the synthesis, through Bt technology, of azo dye-labeled terpenes, sugars, and steroids (2009S1708), and fluorescent detection of biological thiols such as L-cysteine, glutathione, and L-penicillamine was achieved by reaction with N-coumarin-3-carbonyl benzotriazoles (2011S1494). 

The GSH content of freshly isolated rabbit Clara cells was 2.0310.59 nmol/10 cells it was depleted to 0.7510.06 nmol/10 cells by incubating with 200 (JiM diethyl maleate for 20 min (Horton et al. 1987). Cysteine was best able to support resynthesis of GSH. There was no evidence for participation of a cystathionine pathway for glutathione synthesis. In steady-state conditions, the GSH measured in isolated mouse Clara cells was in the femtomole range, but varied 4-fold between individual cells (West et al. 2000). Clara cells analysed in situ and in vitro confirmed this heterogeneity. The response of these cells to compounds that modulate GSH was also variable. Dimethyhnaleate depleted GSH, whereas GSH monoethylester augmented it. However, both acted nonuniformly in isolated Clara cells. The depletion of intracellular GSH caused a striking decrease in cell viability upon incubation with naphthalene. 

The GSH content of freshly isolated rabbit type II pneumocytes was 0.43 0.11 nmol/10 cells it was depleted to 0.15 0.03 nmol/10 cells by incubating with 200 fiM diethyl maleate for 20 min (Horton et al. 1987). Cysteine was best able to support resynthesis of GSH. There was no evidence for participation of a cystathionine pathway for glutathione synthesis. 

When glutathione synthesis was inhibited by bu-thionine sulfoximine so that were was a 50 % depletion of glutathione, the immortalised rat mesencephalic cell line CSM14.1.4 showed an enhanced synergistic toxicity of sulphite and peroxynitrite (Marshall et al. 1999). Because sulphite is present normally in the brain as a product of cysteine metabolism, and because increased peroxynitrite formation has been reported in Parkinson s disease, these events might contribute to neuronal death. 

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