Abstract
Many biological oxidations proceed via formation of radicals and/or peroxides. The tripeptide γ-glutamylcysteinylglycine or reduced glutathione (GSH) is known to protect cells against oxidative damage. This function can be executed in three different ways:
-
1.
GSH, like other thiols, can act as a radical acceptor1, thereby forming the disulphide GSSG (oxidized glutathione):
$$GSH + R. \to GS.RH2GS. \to GSSG$$ -
2.
Peroxides may be eliminated either by catalase (in case of hydrogen (peroxide) or by GSH in the glutathione peroxidase reaction2:
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3.
Oxidative reactions may also give rise to formation of disulphide bridges in proteins, often leading to unfolding and denaturation of these proteins. Glutathione is able to restore the function of these proteins by reduction of such disulphides, with formation of mixed disulphides as intermediates3,4:
$$GSH + R - S - S - R' \rightleftharpoons G - S - S - R + R' - SHGSH + G - S - S - R \rightleftharpoons GSSG + R - SH$$
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References
Kossower, E. M. (1976). Chemical properties of glutathione. In I. M. Arias and W. B. Jakoby (eds.). Glutathione, Metabolism and Function, p. 1 (New York: Raven Press)
Flohé, L. and Giinzler, W. A. (1974). Glutathione peroxidase. In L. Flohé, H. Ch. Benöhr, H. Sies, H. D. Waller and A. Wendel (eds.). Glutathione. Proc. 16th Conf. German Soc. Biol. Chem., p. 132 (Stuttgart: Georg Thieme Publishers)
Flohé, L. and Giinzler, W. A. (1976). Glutathione-dependent enzymatic oxidoreduction reactions. In I. M. Arias and W. B. Jakoby (eds.). Glutathione, Metabolism and Function, p. 17. (New York: Raven Press)
Hartter, P. and Weber, U. (1974). The thiol-disulfide exchange reactions of asymmetric disulfides of cysteine and cyclic cysteine peptides with G-SH. In L. Flohé, H. Ch. Benöhr, H. Sies, H. D. Waller and A. Wendel (eds.). Glutathione. Proc. 16th Conf. German Soc. Biol. Chem., p. 29. (Stuttgart: Georg Thieme Publishers)
Beutler, E. and Srivastava, S. K. (1974). G-SH metabolism of the lens. In L. Flohé, H. Ch. Benöhr, H. Sies, H. D. Waller and A. Wendel (eds.). Glutathione. Proc. 16th Conf. German Soc. Biol. Chem., p. 201. (Stuttgart: Georg Thieme Publishers)
Srivastava, S. K. and Beutler, E. (1970). Glutathione metabolism of the erythrocyte. The enzymic cleavage of glutathione-haemoglobin preparations by glutathione reductase. Biochem. J., 119, 353
Beutler, E. (1974). Glutathione reductase. In L. Flohé, H. Ch. Benöhr, H. Sies, H. D. Waller and A. Wendel (eds.). Glutathione. Proc. 16th Conf. German Soc. Biol. Chem., p. 109. (Stuttgart: Georg Thieme Publishers)
Kossower, E. M. and Kossower, N. S. (1976). Chemical basis of the perturbation of glutathione-glutathione disulfide status of biological systems by diazenes. In I. M. Arias and W. B. Jakoby (eds.). Glutathione, Metabolism and Function, p. 139. (New York: Raven Press)
Kossower, E. M. and Kossower, N. S. (1974). Manifestations of changes in the G-SH — G-S-S-G status of biological systems. In L. Flohé, H. Ch. Benöhr, H. Sies, H. D. Waller and A. Wendel (eds.). Glutathione. Proc. 16th Conf. German Soc. Biol. Chem., p. 287. (Stuttgart: Georg Thieme Publishers)
Hochberg, A., Rigby, M. and Dimant, E. (1961). The incorporation in vitro of glycine and L-glutamic acid into glutathione of human erythrocytes. Biochim. Biophys. Acta, 90, 464
Boivin, P. and Galand, C. (1965). La synthèse du glutathion au cours de l’anémie hémolytique congénitale avec déficit en glutathion réduit. Déficit congénital en glutathion synthétase érythrocytaire? Nouv. Rev. Franç Hématol., 5, 707
Meister, A. (1974). Biosynthesis and utilization of glutathione; the γ- glutamyl cycle and its function in amino acid transport. In L. Flohé, H. Ch. Benöhr, H. Sies, H. D. Waller and A. Wendel (eds.). Glutathione. Proc. 16th Conf. German Soc. Biol. Chem., p. 56. (Stuttgart: Georg Thieme Publishers)
Meister, A. (1976). Glutathione and the γ-glutamyl cycle. In I. M. Arias and W. B. Jakoby (eds.). Glutathione, Metabolism and Function, p. 35. (New York: Raven Press)
Chasseaud, L. F. (1974). Glutathione S-transferases. In L. Flohé, H. Ch. Benöhr, H. Sies, H. D. Waller and A. Wendel (eds.). Glutathione. Proc. 16th Conf. German Soc. Biol. Chem., p. 90. (Stuttgart: Georg Thieme Publishers)
Chasseaud, L. F. (1976). Conjugation with glutathione and mercapturic acid excretion. In I. M. Arias and W. B. Jakoby (eds.). Glutathione, Metabolism and Function, p. 77. (New York: Raven Press)
Srivastava, S. K. and Beutler, E. (1969). The transport of oxidized glutathione from human erythrocytes. J. Biol. Chem., 244, 9
Srivastava, S. K. and Beutler, E. (1969). Cataract produced by tyrosinase and tyrosine systems in rabbit lens in vitro. Biochem. J., 112, 421
Sies, H., Gerstenecker, C., Menzel, H. and Flohé, L. (1972). Oxidation in the NADP system and release of GSSG from hemoglobin-free perfused rat liver during peroxidatic oxidation of glutathione by hydroperoxides. FEBS Lett., 27, 171
Smith, J. E. (1974). Relationship of in vivo erythrocyte glutathione flux to the oxidized glutathione transport system. J. Lab. Clin. Med., 83, 444
Misra, H. P. and Fridovich, I. (1972). The generation of superoxide radical during the autoxidation of hemoglobin. J. Biol. Chem., 247, 6960
Jacob, H. S., Ingbar, S. H. and Jandl, H. S. (1965). Oxidative hemolysis and erythrocyte metabolism in hereditary acatalasia. J. Clin. Invest., 44, 1187
Aebi, H. and Suter, H. (1974). Protective function of reduced glutathione (G-SH) against the effect of prooxidative substances and of irradiation in the red cell. In L. Flohé, H. Ch. Benöhr, H. Sies, H. D. Waller and A. Wendel (eds.). Glutathione. Proc. 16th Conf. German Soc. Biol. Chem., p. 192. (Stuttgart: Georg Thieme Publishers)
Gross, R. T., Bracci, R., Rudolph, N., Schroeder, E. and Kochen, J. A. (1967). Hydrogen peroxide toxicity and detoxification in the erythrocytes of newborn infants. Blood, 29, 481
Zeller, E. A. (1953). Contribution to the enzymology of the normal and cataractous lens. III. On the catalase of the crystalline lens. Am. J. Ophthalmol., 36, 51
Strauss, R. R., Paul, B. B., Jacobs, A. A. and Sbarra, A. J. (1969). The role of the phagocyte in host-parasite interactions. XIX. Leukocytic glutathione reductase and its involvement in phagocytosis. Arch. Biochem. Biophys., 135, 265
Konrad, P. N., Richards, F., Valentine, W. N. and Paglia, D. E. (1972). γ-Glutamyl cysteine synthetase deficiency; a cause of hereditary hemolytic anemia. N. Engl. J. Med., 286, 557
Oort, M., Loos, J. A. and Prins, H. K. (1961). Hereditary absence of reduced glutathione in the erythrocytes. A new clinical and biochemical entity. Vox Sang., 6, 370
Prins, H. K., Oort, M., Loos, J. A., Zürcher, C. and Beckers, T. A. (1966). Congenital non-spherocytic hemolytic anaemia associated with glutathione deficiency of the erythrocytes. Hematologic, biochemical and genetic studies. Blood. 27, 145
Boivin, P., Galand, C., André, R. and Debray, J. (1966). Anémies hémo- lytiques congénitales avec déficit isolé en glutathion réduit par déficit en glutathion synthétase. Nouv. Rev. Franç. Hématol., 6, 859
Boivin, P., Galand, C. and Bernard, J. F. (1974). Deficiencies in G-SH biosynthesis. In L. Flohé, H. Ch. Benöhr, H. Sies, H. D. Waller and A. Wendel (eds.). Glutathione. Proc. 16th Conf. German Soc. Biol. Chem., p. 146. (Stuttgart: Georg Thieme Publishers)
Mohler, D. N., Majerus, P. W., Minnich, V., Hess, C. E. and Garrick, M. D. (1970). Glutathione synthetase deficiency as a cause of hereditary hemolytic disease. N. Engl. J. Med., 283, 1253
Larsson, A., Zetterström, R., Hagenfeldt, L., Andersson, R., Dreborg, S. and Hornell, H. (1974). Pyroglutamic aciduria (5-oxoprolinuria), an inborn error of glutathione metabolism. Pediatr. Res., 8, 852
Larsson, A., Zetterström. R., Hörnell, H. and Porath, U. (1976). Erythrocyte glutathione synthetase in 5-oxoprolinuria: Kinetic studies of the mutant enzyme and detection of heterozygotes. Clin. Chim. Acta. 73, 19
Marstein, S., Jellum, E., Halpern, B., Eldjarn, L. and Perry, T. L. (1976). Biochemical studies of erythrocytes in a patient with pyroglutamic acidemia (5-oxoprolinemia). N. Engl. J. Med., 295, 406
Spielberg, S. P., Kramer, L. I., Goodman, S. I., Butler, J., Tietze, F., Quinn, P. and Schulman, J. D. (1977). 5-Oxoprolinuria: biochemical observations and case report. J. Pediatr., 91, 237
Necheles, T. F., Maldonado, N., Barquet-Chediak, A. and Allen, D. M. (1969). Homozygous erythrocyte glutathione-peroxidase deficiency: clinical and biochemical studies. Blood, 33, 164
Necheles, T. F. (1974). The clinical spectrum of glutathione-peroxidase deficiency. In L. Flohé, H. Ch. Benöhr, H. Sies, H. D. Waller and A. Wendel (eds.). Glutathione. Proc. 16th Conf. German Soc. Biol. Chem., p. 173. (Stuttgart: Georg Thieme Publishers)
Necheles, T. F., Boles, T. A. and Allen, D. M. (1968). Erythrocyte glutathione peroxidase deficiency and hemolytic disease of the newborn infant. J. Pediatr., 72, 319
Boivin, P., Galand, C., Hakim, J. and Guéroult, N. (1969). Anémie hémolytique avec déficit en glutathione peroxydase chez un adulte. Enzym. Biol. Clin., 10, 68
Boivin, P., Galand, C., Hakim, J. and Blery, M. (1970). Déficit en glutathionperoxidase érythrocytaire et anémie hémolitique médicamenteuse. Presse Med., 78, 171
Benedetti, P. (1966). Glutathione peroxidase deficiency. Symposium on Problems of Fetal Distress. (Siena, Italy)
Beutler, E. (1971). Abnormalities of the hexose monophosphate shunt. Semin. Hematol., 8, 311
Beutler, E. (1969). Effect of flavin compounds on glutathione reductase activity: in vivo and in vitro studies. J. Clin. Invest., 48, 1957
Löhr, G. W., Blume, K. G., Rüdiger, H. W. and Arnold, H. (1974). Genetic variability in the enzymatic reduction of oxidized glutathione. In L. Flohé, H. Ch. Benöhr, H. Sies, H. D. Waller, and A. Wendel (eds.). Glutathione. Proc. 16th Conf. German Soc. Biol. Chem., p. 165. (Stuttgart: Georg Thieme Publishers)
Staal, G. E. J., Helleman, P. W., de Wael, J. and Veeger, C. (1969). Purification and properties of an abnormal glutathione reductase from human erythrocytes. Biochim. Biophys. Acta, 185, 39
Loos, J. A., Roos, D., Weening, R. S. and Houwerzijl, J. (1976). Familial deficiency of glutathione reductase in human blood cells. Blood, 48, 53
Brewer, G. J. (1969). 6-Phosphogluconate dehydrogenase and glutathione reductase. In J. J. Yunis (ed.). Biochemical Methods in Red Cell Genetics, p. 139. (New York and London: Academic Press)
Lausecker, C., Heidt, P., Fischer, D., Hartleyb, H. and Löhr, G. W. (1965). Anémie hémolytique constitutionnelle avec déficit en 6-phosphogluconate deshydrogénase. Arch. Franç. Pediatr., 22, 789
Scialom, C., Najean, Y. and Bernard, J. (1966). Anémie hémolytique congénital non-sphérocytaire avec déficit incomplet en 6-phosphogluconate deshydrogénase. Nouv. Rev. Franç. Hématol., 6, 452
Dern, R. J., Brewer, G. J., Tashian, R. E. and Shows, T. B. (1966). Hereditary variation of erythrocytic 6-phosphogluconate dehydrogenase. /. Lab. Clin. Med., 67, 255
Kinoshita, J. H. and Merola, L. O. (1973). Oxidation of thiol groups of the human lens. In The Human Lens — in Relation to Cataract. Ciba Foundation Symposium 19 (new series), p. 173. (Amsterdam: Associated Scientific Publishers)
Truscott, R. J. W. and Augusteyn, R. C. (1977). Oxidative changes in human lens proteins during senile nuclear cataract formation. Biochim. Biophys. Acta, 492, 43
Zinkham, W. H. (1961). A deficiency of glucose-6-phosphate dehydrogenase activity in lens from individuals with primaquine-sensitive erythrocytes. Bull. Johns Hopkins Hosp., 109, 206
Westring, D. W. and Pisciotta, A. V. (1966). Anemia, cataracts, and seizures in patients with glucose-6-phosphate dehydrogenase deficiency. Arch. Intern. Med., 118, 385
Helge, H. and Borner, K. (1966). Kongenitale nichtsphärozytäre hämolytische Anämie, Kataract und Glukose-6-phosphat-dehydrogenase Mangel. Deutsch. Med. Wochenschr., 91, 1584
Cooper, M. R., De Chatelet, L. R., McCall, C. E., La Via, M. F., Spurr, C. L. and Baehner, R. L. (1972). Complete deficiency of leukocyte glucose- 6-phosphate dehydrogenase with defective bactericidal activity. J. Clin. Invest., 51, 769
Johnston, R. B., Jr. and Baehner, R. L. (1970). Improvement of leukocyte bactericidal activity in chronic granulomatous disease. Blood, 35, 350
Patriarca, P., Cramer, R., Moncalvo, S., Rossi, F. and Romeo, D. (1971). Enzymatic basis of metabolic stimulation in leukocytes during phagocytosis: The role of activated NADPH oxidase. Arch. Biochem. Biophys., 145, 255
Hohn, D. C. and Lehrer, R. I. (1975). NADPH oxidase deficiency in X- linked chronic granulomatous disease. J. Clin. Invest., 55, 707
Curnutte, J. T., Kipnes, R. S. and Babior, B. M. (1975). Defect in pyridine nucleotide dependent superoxide production by a particulate fraction from the granulocytes of patients with chronic granulomatous disease. N. Engl. J. Med., 293, 628
Segal, A. W. and Peters, T. J. (1976). Characterisation of the enzyme defect in chronic granulomatous disease. Lancet, i, 1363
Briggs, R. T., Karnovsky, M. L. and Karnovsky, M. J. (1977). Hydrogen peroxide production in chronic granulomatous disease. A cytochemical study of reduced pyridine nucleotide oxidase. J. Clin. Invest., 59, 1088
Baehner, R. L., Johnston, R. B., Jr. and Nathan, D. G. (1972). Comparative study of the metabolic and bactericidal characteristics of severely glucose- 6-phosphate dehydrogenase-deficient polymorphonuclear leukocytes and leukocytes from children with chronic granulomatous disease. J. Reticuloendothel. Soc., 12, 150
Gray, G. R., Klebanoff, S. J., Stamatoyannopoulos, G., Austin, T., Naiman, S. C., Yoshida, A., Kliman, M. R. and Robinson, G. S. F. (1973). Neutrophil dysfunction, chronic granulomatous disease and nonspherocytic haemo- lytic anaemia caused by complete deficiency of glucose-6-phosphate dehydrogenase. Lancet, ii, 530
Rodey, G. E., Jacob, H. S., Holmes, B., McArthur, J. R. and Good, R. A. (1970). Leucocyte G-6-PD levels and bactericidal activity. Lancet, i, 355
Holmes-Gray, B. and Good, R. A. (1971). Chronic granulomatous disease of childhood. In R. A. Good and D. W. Fisher (eds.). Immunobiology, Current Knowledge of Basic Concepts in Immunology and their Clinical Applications, p. 55. (Stanford: Sinauer Associates, Inc.)
Reed, P. W. (1969). Glutathione and the hexose monophosphate shunt in phagocytizing and hydrogen peroxide-treated rat leukocytes. J. Biol. Chem., 244, 2459
Noseworthy, J. Jr. and Karnovsky, M. L. (1972). Role of peroxide in the stimulation of the hexose monophosphate shunt during phagocytosis by polymorphonuclear leukocytes. Enzym., 13, 110
Vogt, M. T., Thomas, C., Vassallo, C. L., Basford, R. E. and Gee, J. B. L. (1971). Glutathione-dependent peroxidative metabolism in the alveolar macrophage. J. Clin. Invest., 50, 401
Mandell, G. L. (1972). Functional and metabolic derangements in human neutrophils induced by a glutathione antagonist. J. Reticuloendothel. Soc., 11, 129
Oliver, J. M., Albertini, D. F. and Berlin, R. D. (1976). Effects of glutathione- oxidizing agents on microtubule assembly and microtubule-dependent surface properties of human neutrophils. J. Cell. Biol., 71, 921
Holmes-Gray, B., Haseman, J., Buron, S., Saccoccia, P. and Good, R. A. (1971). The relationship of glutathione levels and metabolism of human leukocytes. Fed. Proc., 30, 693Abs.
Holmes, B., Park, B. H., Malawista, S. E., Quie, P. G., Nelson, D. L. and Good, R. A. (1970). Chronic granulomatous disease in females. A deficiency of leukocyte glutathione peroxidase. N. Engl. J. Med., 283, 217
Baehner, R. L., Gilman, N. and Karnovsky, M. L. (1970). Respiration and glucose oxidation in human and guinea-pig leukocytes: comparative studies. J. Clin. Invest., 49, 692
Rossi, F., Romeo, D. and Patriarca, P. (1972). Mechanism of phagocytosis- associated oxidative metabolism in polymorphonuclear leukocytes and macrophages. J. Reticuloendothel. Soc., 12, 127
Burchill, B. R., Oliver, J. M., Pearson, C. B., Leinbach, E. D. and Berlin, R. D. (1977). Microtubule dynamics and glutathione metabolism in phago- cytizing human polymorphonuclear leukocytes. J. Cell. Biol., 76, 439
Quie, P. G., Kaplan, E. L., Page, A. R., Gruskay, F. L. and Malawista, S. E. (1968). Defective polymorphonuclear leukocyte function and chronic granulomatous disease in two female children. N. Engl. J. Med., 278, 976
Johnston, R. B. Jr. and Newman, S. L. (1977). Chronic granulomatous disease. In The Pediatric Clinics of North America, Vol. 24. p. 365. (Philadelphia: W. B. Saunders)
Windhorst, D. B. and Katz, E. D. (1972). Normal enzyme activities in chronic granulomatous disease leukocytes. J. Reticuloendothel. Soc., 11, 400
De Chatelet, L. R., Shirley, P. S. and McPhail, L. C. (1976). Normal leukocyte glutathione peroxidase activity in patients with chronic granulomatous disease. J. Pediatr., 89, 598
Malawista, S. E. and Gifford, R. H. (1975). Chronic granulomatous disease of childhood (GCD) with leukocyte glutathione peroxidase (LPG) deficiency in a brother and sister: a likely autosomal recessive inheritance. Clin. Res., 23, 416Abs
Matsuda, I., Oka, Y., Taniguchi, N., Furuyama, M., Kodama, S., Arashima, S. and Mitsuyama, T. (1976). Leukocyte glutathione peroxidase deficiency in a male patient with chronic granulomatous disease. J. Pediatr., 88, 581
Serfass, R. E. and Ganther, H. E. (1975). Defective microbicidal activity in glutathione peroxidase-deficient neutrophils of selenium-deficient rats. Nature (London), 255, 640
Babior, B. M., Kipnes, R. S. and Curnutte, J. T. (1973). Biological defense mechanisms. The production by leukocytes of superoxide, a potential bactericidal agent. J. Clin. Invest., 52, 741
Weening, R. S., Roos, D., Van Schaik, M. L. J., Voetman, A. A., De Boer, M. and Loos, J. A. (1978). The role of glutathione in the oxidative metabolism of phagocytic leukocytes. Studies in a family with glutathione reductase deficiency. In F. Rossi, P. L. Patriarca and D. Romeo (eds.). Movement, Metabolism and Bactericidal Mechanisms of Phagocytes, p. 277. (Padova: Piccin Medical Books)
Spielberg, S. P., Boxer, L. A., Oliver, J. M., Butler, E. J. and Schulman, J. D. (1977). Altered phagocytosis and microtubule function in leukocytes from a patient with severe glutathione synthetase deficiency (5-oxoprolinuria). In Proc. Intern. Symp. Inborn Errors of Metabolism in Man. (Basel: S. Karger) (In press)
Oliver, J. M., Spielberg, S. P., Pearson, C. B. and Schulman, J. D. (1978). Microtubule assembly and function in normal and glutathione synthetase- deficient polymorphonuclear leukocytes. J. Immunol., 120, 1131
Roos, D. Unpublished observations
Aebi, H. and Suter, H. (1969). Catalase. In J. J. Yunis (ed.). Biochemical Methods in Red Cell Genetics, p. 255. (New York: Academic Press)
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Roos, D., Weening, R.S., Loos, J.A. (1979). The protective role of glutathione. In: Güttler, F., Seakins, J.W.T., Harkness, R.A. (eds) Inborn Errors of Immunity and Phagocytosis. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-6197-8_18
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