Redox Control of Glutathione and Thioredoxin Reductases

  • Juan López-Barea
  • Jose Antonio Bárcena
Part of the NATO ASI Series book series (NSSA, volume 7)


Redox interconversion was discovered in the seventies, when activation of several photosynthetic enzymes by reduced thioredoxin (1), and redox control of NO 3 -, NO 2 -, and NADP+-reductases were first described (2). Regulation of many enzymes by -SH/-SS- exchange has been recently reported, either by direct reaction with low Mw thiols or disulfides, or in a process catalyzed by thiol-transferases (3). Glutathione and thioredoxin reductases are two FAD-containing NADP+-disulfide oxidoreductases, using NADPH to reduce the -SS- groups of glutathione and thioredoxin (1, 4, 5). Both enzymes and their reduced products connect the NADP+/NADPH couple with the pools of low and high Mw thiols and disulfides; then, a general regulatory mechanism could be envisaged if the activities of such enzymes were redox controlled.


Glutathione Reductase Mixed Disulfide Yeast Enzyme Full Reactivation Diaphorase Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    B. B. Buchanan, Role of light in the regulation of chloroplast enzymes, Annu Rev Plant Physiol. 31: 341 (1980).CrossRefGoogle Scholar
  2. 2.
    M. G. Guerrero, J. M. Vega, and M. Losada, The assimilatory NO3-reducing system and its regulation, Annu Rev Plant Physiol. 32: 169 (1981).CrossRefGoogle Scholar
  3. 3.
    D. M. Ziegler, Role of reversible oxidation-reduction of enzyme thiolsdisulfides in metabolic regulation, Annu Rev Biochem. 54: 305 (1985).PubMedCrossRefGoogle Scholar
  4. 4.
    A. Meister, and M. E. Anderson, Glutathione, Annu Rev Biochem. 52: 711 (1983).PubMedCrossRefGoogle Scholar
  5. 5.
    A. Holmgren, Thioredoxin, Annu Rev Biochem. 54: 237 (1985).PubMedCrossRefGoogle Scholar
  6. 6.
    J. López-Barea, and C. Y. Lee, Mouse-liver glutathione reductase. Purification, kinetics, and regulation, Eur J Biochem. 98: 487 (1979).PubMedCrossRefGoogle Scholar
  7. 7.
    M. C. Pinto, A. M. Mata, and J. López-Barea, Reversible inactivation of S. cerevisiae glutathione reductase under reducing conditions, Arch Biochem Biophys. 228: 1 (1984).PubMedCrossRefGoogle Scholar
  8. 8.
    M. C. Pinto, A. M. Mata, and J. López-Barea, The redox interconversion mechanism of S. cerevisiae glutathione reductase, Eur J Biochem. 151: 275 (1985).PubMedCrossRefGoogle Scholar
  9. 9.
    A. M. Mata, M. C. Pinto, and J. López-Barea, Redox interconversion of glutathione reductase from E. coli. A study with pure enzyme and cell-free extracts, Mol Cell Biochem. 67: 65 (1985).Google Scholar
  10. 10.
    A. M. Mata, M. C. Pinto, and J. L pez-Barea, Redox interconversion of E. E. coli glutathione reductase. A study with permeabilized and intact cells, Mol Cell Biochem. 68: 121 (1985).PubMedCrossRefGoogle Scholar
  11. 11.
    J. Peinado, A. Llobell, and J. López-Barea, Effect of EDTA and oxidizable substrates on the redox interconversion of glutathione reductase in S. cerevisiae cell-free extracts, submit. to Biochim Biophys Acta.Google Scholar
  12. 12.
    J. A. Barcena, E. Martinez-Galisteo, C. Gß-Alfonso, and J. Lpó ez-Barea, NADPH and oxidized thioredoxin mediate redox interconversion of calf-liver and E. coli thioredoxin reductase, submit. to Biochem J.Google Scholar
  13. 13.
    E. Martinez-Gâlisteo, “Ph. D. Dissertation,” Universidad de Cardoba, Spain (1987).Google Scholar
  14. 14.
    C. Garcia-Alfonso, “Ph. D. Dissertation,” Universidad de Córdoba, Spain (1987).Google Scholar
  15. 15.
    C. S. Tsai, and J. R. P. Godin, Multifunctional activities of yeast glutathione reductase, Int J Biochem. 19: 337 (1987).PubMedCrossRefGoogle Scholar
  16. 16.
    T. P. M. Akerboom, and H. Sies, Assay of glutathione, glutathione disulfide, and glutathione mixed disulfides in biological samples, Methods Enzymol. 77: 373 (1981).PubMedCrossRefGoogle Scholar
  17. 17.
    P. A. Karplus, and G. E. Schulz, Refined structure of glutathione reductase at 1.54 A resolution, J Mol Biol. 195: 701 (1987).PubMedCrossRefGoogle Scholar
  18. 18.
    E. F. Pal, and G. E. Schulz, The catalytic mechanism of glutathione reductase as derived from X-ray diffraction analyses of reaction intermediates, J Biol Chem. 258: 1752 (1983).Google Scholar
  19. 19.
    V. Massey, and S. Ghisla, Role of charge-transfer interactions in Reno-protein catalysis, Ann N Y Aced Sci. 227: 446 (1974).CrossRefGoogle Scholar
  20. 20.
    A. Llobell, V. M. Ferndndez, and J. Lapez-Barea, Electron transfer between reduced methyl viologen and GSSG: a new assay of S. cerevisiae glutathione reductase, Arch Biochem Biophys. 250:373 (1986)PubMedCrossRefGoogle Scholar
  21. 21.
    J. L. Plummer, B. R. Smith, H. Sies, and J. R. Bend, Chemical depletion of glutathione in vivo, Methods Enzymol 77: 50 (1981).PubMedCrossRefGoogle Scholar
  22. 22.
    H. Sies, Biochemistry of oxidative stress, Angew Chem. 25: 1058 (1986).CrossRefGoogle Scholar
  23. 23.
    A. Llobell, A. López-Ruiz, J. Peinado, and J. López-Barea, Glutathione reductase directly mediates the stimulation of yeast glucose-6-phosphate dehydrogenase by GSSG, Biochem J. 249: 293 (1988).PubMedGoogle Scholar
  24. 24.
    M. E. O’Donnell, and C. H. Williams Jr.,-Proton stoichiometry in the reduction of FAD and disulfide in Escherichia coli thioredoxin reductase. Evidence for a base at the active site, J Biol Chem. 258: 13795 (1983).PubMedGoogle Scholar
  25. 25.
    N. Lambert, and R. B. Freedman, The latency of rat liver microsomal protein disulphide isomerase, Biochem J. 228: 635 (1985).PubMedGoogle Scholar
  26. 26.
    K. Axelsson, S. Eriksson, and B. Mannervik, Purification and characterization of cytoplasmic thioltransferase (glutathione:disulfide oxidoreductase) from rat liver, Biochemistry 17: 2978 (1978).PubMedCrossRefGoogle Scholar
  27. 27.
    B. Rozell, H. A. Hansson, M. Luthman, and A. Holmgren, Iormunohistochemical localization of thioredoxin and thioredoxin reductase in adult rats, Eur J Cell Biol. 38: 79 (1985).PubMedGoogle Scholar
  28. 28.
    M. P. Czech, Differential effects of sulfhydryl reagents on activation and deactivation of the fat cell hexose transport system, J Biol Chem. 251: 1164 (1976).PubMedGoogle Scholar
  29. 29.
    C. C. Malbon, S. T. George, and C. P. Moxham, Intramolecular disulfide bridges: avenues to receptor activation?, Trends Biochem Sci. 12: 172 (1987).CrossRefGoogle Scholar
  30. 30.
    E. Hazum, K.- J. Chang, and P. Cuatrecasas, Role of disulfide and sulphydryl groups in clustering of enkephalin receptors in neuroblastoma cells, Nature. 282: 626 (1979).PubMedCrossRefGoogle Scholar
  31. 31.
    G. Thomas, V. A. Skrinska, and F. V. Lukas, The influence of glutathione and other thiols on human platelet aggregation, Thromb Res. 44: 859 (1986).PubMedCrossRefGoogle Scholar
  32. 32.
    P. N. Kao, and A. Karlin, Acetylcholine receptor binding site contains a disulfide cross-link between adjacent half cysteinyl residues, J Biol Chem. 261: 8085 (1986).PubMedGoogle Scholar
  33. 33.
    H. A. Jonas, and L. E. Harrison, Disulfide reduction alters the immunoreactivity and increases affinity of insulin-like growth-factor-I receptors in human placenta, Biochem J. 236: 417 (1986).PubMedGoogle Scholar
  34. 34.
    L. J. Pyke, A. T. Eakes, and E. G. Krebs, Characterization of affinity-purified insulin receptor/kinase. Effect of dithiothreitol on receptor/kinase function, J Biol Chem. 261: 3782 (1986).Google Scholar
  35. 35.
    N. Takeguchi, and Y. Yaniazaki, Disulfide cross-linking of H,K-ATPase opens Cl-conductance, triggering proton uptake in gastric vesicles. Studies with specific inhibitors, J Biol Chem. 261: 2560 (1986).PubMedGoogle Scholar
  36. 36.
    C. E. Olson, A. H. Soll,,*nd N. Kaplewitz, Modulating effect of thioldisulfide status on (4C)aminopyrine accumulation in the isolated parietal cell, J Biol Chem. 260: 8020 (1985).PubMedGoogle Scholar
  37. 37.
    B. Persson, and J. Rydst8m, Evidence for a role of a vicinal thiol in catalysis and proton pumping in mitochondrial nicotinamide nucleotide transhydrogenase, Biochem Biophys Res Commun. 142: 573 (1987).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Juan López-Barea
    • 1
  • Jose Antonio Bárcena
    • 1
  1. 1.Depto. de Bioquímica y Biología Molecular (F. Veterinaria)Universidad de CórdobaCórdobaEspaña

Personalised recommendations