Synthesis glutathione

Gotoh, N., Graham, A., Niki, E. anel Darley-Usmar, V.M. (1993). Inhibition of glutathione synthesis increases the toxicity of oxidised LDL to human monoctites and macrophages. Biochem. J. 296, 151-154. 

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. 

Aminoacid peptides (c.f. Z-/ -Ala-/ -Ala-OC2H5, 75% yield) have also been prepared by this pyrazolide method. 31 A glutathione synthesis was accomplished by the pyr-azolide method in the following way [32]... 

Lu, S.C. (1999) Regulation of hepatic glutathione synthesis current concepts and controversies. FASEB Journal, 13, 1169-1183. 

On the other hand, hydroquinone (3 pmol/L) prevented the staurosporine-induced apoptosis of HL-60 and the IL-3-dependent murine myeloblastic (32D) cell line it also prevented apoptosis of the 32D cells observed in the absence of IL-3. The myeloperoxidase inhibitor indomethacin opposed the effect of hydroquinone on staurosporine-induced apoptosis of HL-60 cells (Hazel et al., 1995, 1996b). Pretreatment of human leukaemia cells ML-1 with buthionine sulfoximine (100 pmol/L for 24 h), in order to decrease their glutathione content, increased the susceptibility of these cells to hydroquinone-induced inhibition of differentiation caused by phorbol acetate pretreatment with l,2-dithiole-3-thione, which induces reduced glutathione synthesis, prevented the differentiation inhibition of hydroquinone. Treatment of DBA/2 mice with 1,2-dithiole-3-thione, which increased the activity of quinone reductase of bone-marrow stromal cells by 50%, decreased the susceptibility of these cells towards hydroquinone (Trush et al., 1996). 

M. Runnegar, K. Shou-Ming, Z. Ya-Zhen and C. Shelly, Inhibition of reduced glutathione synthesis by cyanobacterial alkaloid cylindrospermopsin in cultured rat hepatocytes, Biochem. Pharmacol., 49 (1995) 219-255. 

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. 

Yoshida, K., J. Hirokawa, S. Tagami, Y. Kawakami, Y. Urata, and T. Kondo. 1995. Weakened cellular scavenging activity against oxidative stress in diabetes mellitus Regulation of glutathione synthesis and efflux. Diabetologia. 38 201-10. 

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. 

Glutathione synthesis is impaired in patients at the level of the GCL enzyme, as measured in fibroblasts. In addition, genetic analysis showed an association between schizophrenia and the two GCL subunits. These findings are consistent with low brain and cerebrospinal fluid (CSF) glutathione levels. 

A redox/antioxidant dysregulation due to an impairment of glutathione synthesis of genetic origin is a vulnerability factor for schizophrenia. 

Castagne V, Cuenod M, Do KQ. 2004a. An animal model with relevance to schizophrenia Sex-dependent cognitive deficits in osteogenic disorder-Shionogi rats induced by glutathione synthesis and dopamine uptake inhibition during development. Neuroscience 123 821-834. 

Gysin R, Kraftsik R, Sandell J, Bovet P, Chappuis C, et al. 2007. Impaired glutathione synthesis in schizophrenia Convergent genetic and functional evidence, Proc Natl Acad Sci USA 104 16621-16626. 

Shi ZZ, et al. 2000. Glutathione synthesis is essential for mouse development but not for cell growth in culture. Proc Natl Acad Sci USA 97 5101-5106. 

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

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