The thiol-disulphide interchange reaction is important in maintaining the thiol status of cells (Figure 1, reaction 10):
The activation parameters for the thiolate-disulphide exchange reactions resemble those for other nucleophilic displacement reactions of thiols, suggesting that the exchange is a nucleophilic displacement on sulphur.
The thiol status of a biological system may be described as the distribution of thiols, exogenous or endogenous, among different chemical forms, including thiols (GSH, protein thiols), thiol esters (acyl-CoA) and disul-phides (GSSG, CoASSCoA, protein-GS mixed disulphides, and proteinprotein disulphides).
A quantitative expression of thiol status can be given as follows:
Thiol status (TS): thiol, directly measurable forms, mM / total, all forms of thiols and disulphides, mM. (The total includes all types of SH and SS equivalents.) The experimental methods for both quantities must be specified. Thus, for human red blood cells: TS = 3.5 / 4.0.
The relationship of thiol status to enzyme function, metabolic regulation, and cellular structure is not well understood. An enzyme that may be important in regulating thiol status is thiol-transferase.
The redox status of GSH (the ratio GSH/GSSG) is closely related to the thiol status. It is an important parameter for the antioxidant defence and is always markedly shifted in favour of the reduced form. Thus, in spinach chloroplasts, where the activity of glutathione reductase is high while glu-tathione peroxidase is absent, the ratio and in Neuro-
spora crassa (moderate glutathione reductase level; glutathione peroxidase absent) the reduced form is even more dominating
In plant cells GSH fulfils several functions. As an antioxidant GSH protects cell constituents against oxidative stress, e.g. GSH - in cooperation with ascorbate - removes reactive oxygen species which are formed as byproducts of the photosynthesis. Furthermore, GSH accomplishes protective functions by conjugation of xenobiotics and as starting material for the synthesis of phytochelatins for the detoxification of heavy metals. Additionally, GSH serves as storage compound for organic sulphur. Through enzymatic degradation cysteine can be recovered if needed. Novel functions of GSH are emerging (Sies 1999). One is the hopping of nitric oxide between thiol groups in a process known as trans-nitrosation (Al-Mustafa et al. 2001). A major focus of current research is directed to the role of thiols in signalling, i.e. the control and modulation of pathways leading to gene expression (Sies 2001).
Currently, the prospects for the molecular enhancement of glutathione are being explored (Foyer 2001, Anderson 1997). GSH biosynthesis has been studied extensively in plants by overexpressing cysteine syn-
thetase and glutathione synthetase, and a substantial constitutive increase in tissue GSH has thereby been achieved. However, such molecular genetic approaches are not acceptable to the consumer and alternative approaches have to be found. The possibilities for using the plants' own defences against oxidative stress to improve the antioxidant content of plant foods will be explored using GSH and ascorbate as models. The signals involved in triggering high antioxidant accumulation are only poorly understood. Leaves have a high capacity for production of one well-known signal, H202. Intracellular H202 concentrations are low, however, because of control by the antioxidant system. Mutants and transformed plants with specific decreases in key components offer the opportunity to dissect the complex system that maintains redox homeostasis and determines the antioxidant responses.
Further information of importance may be found in several books and reviews, e.g. references (Meister and Anderson 1983, Lamoureux and Rusness 1989, Meister 1983, Sies 1999, Anderson 1997, Wonisch et al. 1997, Heldt and Heldt 1996).
Al-Mustafa A., Sies H., Stahl W. 2001. Sulfur-to-nitrogen transnitrosation: transfer of nitric oxide from S-nitroso compounds to diethanolamine and the role of intermediate sulfur-to-sulfur tansnitrosation. - Toxicology, in press.
Anderson M. E. 1985. Determination of glutathione and glutathione disulfide in biological samples. - Methods Enzymol. 113: 548-555.
Anderson M. E. 1997. Glutathione and glutathione delivery compounds. - In: Sies H. (Ed.), Antioxidants in disease mechanisms and therapy. - Advances in Pharmacology 38: 65-78. - Academic Press.
Berthe-Corti L., Hulsch R., Nevries U., Eckardt-Schupp F. 1992. Use of batch and fed-batch fermentation for studies on the variation of glutathione content and it's influence on the genotoxicity of methyl-nitro-nitrosoguanidine in yeast. - Mutagenesis 7: 25-30.
Esterbauer H., Zollner H., Scholz N. 1975. Reaction of glutathione with conjugated carbon-yls. - Z. Naturfosch. 30c: 466-473.
Esterbauer H., Schaur R. J.. Zollner H. 1991. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. - Free Rad. Biol. Med. 11: 81-128.
Fahey R. C., Newton G. L. 1987. Determination of low-molecular-weight thiols using mono-bromobimane fluorescent labeling and high-performance liquid chromatography. -Methods Enzymol. 143: 85-96.
Foyer Ch. 2001. Prospects for enhancement of soluble antioxidants. - Meeting of the Society for Free Radical Research Europe, Rome 22-24 June 2001, Abstract Volume OC 4.
Griffith O. W., Mulcahy R. T. 1999. The enzymes of glutathione synthesis: gamma-glutamylcysteine synthetase. - Adv. Enzymol. Relat. Areas Mol. Biol. 73: 209267.
Heldt W., Heldt F. 1996. Pflanzenbiochemie. - Spektrum Akademischer Verlag Heidelberg.
Jamieson D. J. 1998. Oxidative stress responses of the yeast Saccharomyces cerevisiae. -Yeast 14: 1511-1527.
Kosower E. M. 1989. Structure and reactions of thiols with special emphasis on glutathione. -In: Dophin D., Avramovic O., Poulson R. (Eds.), Glutathione - Chemical, biochemical, and medical aspects, pp. 103-146, Part A, Wiley, New York.
Lamoureux G. L., Rusness D. G. 1989. The role of glutathione and glutathione-S-transferases in pesticide metabolism, selectivity, and mode of action in plants and insects.- In: Dolphin D., Avramovi O., Poulson R. (Eds.), Glutathione - Chemical, biochemical and medical aspects - Part B. - John Wiley & Sons.
Lau E. P., Niswander L., Watson D., Fall R. R. 1980. Glutathione-S-transferase is present in a variety of microorganisms. - Chemosphere 9: 565-569.
Meister A. 1983. Selective modification of glutathione metabolism. - Science 220: 472-477.
Meister A., Anderson M. E. 1983. Glutathione. - Ann. Rev. Biochem. 52: 711-760.
Newton G. L., Dorian R., Fahey R. C. 1981. Analysis of biological thiols: derivatization with monobromobimane and separation by reverse-phase high-performance liquid chromatography. - Anal. Biochem: 114: 383-387.
Prestera T., Zhang Y., Spencer S. R., Wilczak C. A., Talalay P. 1993. The electrophile counterattack response: protection against neoplasia and toxicity. - Adv. Enzyme Regul. 33: 281-296.
Sies H. 1999. Glutathione and its role in cellular functions. - Free Radic. Biol. Med. 27: 916921.
Sies H. 2001. The thiol connection: an introductory overview. - Meeting of the Society for Free Radical Research Europe, Rome 22-24 June 2001, Abstract Volume OC 32.
Talalay P., Fahey J. W., Holtzclaw W. D., Prestera T., Zhang Y. 1995. Chemoprotection against cancer by phase 2 enzyme induction. - Toxicol. Lett. 82-83: 173-179.
Wonisch W., Hayn M., Schaur R. J., Tatzber F., Kranner I., Grill D., Winkler R., Bilinski T., Kohlwein S. D., Esterbauer H. 1997. Increased stress parameter synthesis in the yeast Saccharomyces cerevisiae after treatment with 4-hydroxy-2-nonenal. -FEBS Lett. 405: 11-15.
Was this article helpful?
Our internal organs, the colon, liver and intestines, help our bodies eliminate toxic and harmful matter from our bloodstreams and tissues. Often, our systems become overloaded with waste. The very air we breathe, and all of its pollutants, build up in our bodies. Today’s over processed foods and environmental pollutants can easily overwhelm our delicate systems and cause toxic matter to build up in our bodies.