Skip to main content
SpringerLink
Log in

Inhibitors of Glyceraldehyde 3-Phosphate Dehydrogenase and Unexpected Effects of Its Reduced Activity

  • Review
  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

The review describes the use of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) inhibitors to study the enzyme and to suppress its activity in various cell types. The main problem of selective GAPDH inhibition is a highly conserved nature of the enzyme active site and, especially, Cys150 environment important for the catalytic action of cysteine sulfhydryl group. Numerous attempts to find specific inhibitors of sperm GAPDH and enzymes from Trypanosoma sp. and Mycobacterium tuberculosis that would not inhibit GAPDH of somatic mammalian cells have failed, which has pushed researchers to search for new ways to solve this problem. The sections of the review are devoted to the studies of GAPDH inactivation by reactive oxygen species, glutathione, and glycating agents. The final section discusses possible effects of GAPDH inhibition and inactivation on glycolysis and related metabolic pathways (pentose phosphate pathway, uncoupling of the glycolytic oxidation and phosphorylation, etc.).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

DHAP:

dihydroxyacetone phosphate

GAPDH:

glyceraldehyde 3-phosphate dehydrogenase

GAPDS:

sperm-specific glyceraldehyde 3-phosphate dehydrogenase

GSH:

reduced glutathione

References

  1. Nagradova, N. K. (1956) Mechanism of action of carnosine on glycolytic oxidation reduction combined with phosphorylation, Biochemistry (Moscow), 21, 17–25.

    CAS  Google Scholar 

  2. Nagradova, N. K. (1965) The effect of histidine and other chelating agents on the activity of 3-phosphoglyceraldehyde dehydrogenase from rabbit muscles, Biochemistry (Moscow), 30, 50–57.

    CAS  Google Scholar 

  3. Schmalhausen, E. V., Nagradova, N. K., Boschi-Muller, S., Branlant, G., and Muronetz, V. I. (1999) Mildly oxidized GAPDH: the coupling of the dehydrogenase and acyl phosphatase activities, FEBS Lett., 452, 219–222.

    Article  CAS  PubMed  Google Scholar 

  4. Danshina, P. V., Schmalhausen, E. V., Avetisyan, A. V., and Muronetz, V. I. (2001) Mildly oxidized glyceraldehyde-3-phosphate dehydrogenase as a possible regulator of glycolysis, IUBMB Life, 51, 309–314.

    Article  CAS  PubMed  Google Scholar 

  5. Dan’shina, P. V., Schmalhausen, E. V., Arutiunov, D. Y., Pleten’, A. P., and Muronetz, V. I. (2003) Acceleration of glycolysis in the presence of the non-phosphorylating and the oxidized phosphorylating glyceraldehyde-3-phosphate dehydrogenases, Biochemistry (Moscow), 68, 593–600.

    Article  Google Scholar 

  6. Seidler, N. W. (2013) Basic biology of GAPDH, Adv. Exp. Med. Biol., 985, 1–36.

    Article  PubMed  Google Scholar 

  7. Sikand, K., Singh, J., Ebron, J. S., and Shukla, G. C. (2012) Housekeeping gene selection advisory: glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and β-actin are targets of miR-644a, PloS One, 7, e47510.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Caradec, J., Sirab, N., Revaud, D., Keumeugni, C., and Loric, S. (2010) Is GAPDH a relevant housekeeping gene for normalisation in colorectal cancer experiments? Br. J. Cancer, 103, 1475–1476.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Muronetz, V. I., Barinova, K. V., Stroylova, Y. Y., Semenyuk, P. I., and Schmalhausen, E. V. (2017) Glyceraldehyde-3-phosphate dehydrogenase: aggregation mechanisms and impact on amyloid neurodegenerative diseases, Int. J. Biol. Macromol., 100, 55–66.

    Article  CAS  PubMed  Google Scholar 

  10. Mazzola, J. L., and Sirover, M. A. (2002) Alteration of intracellular structure and function of glyceraldehyde-3-phosphate dehydrogenase: a common phenotype of neurodegenerative disorders? Neurotoxicology, 23, 603–609.

    Article  CAS  PubMed  Google Scholar 

  11. Tatton, W. G., Chalmers-Redman, R. M., Elstner, M., Leesch, W., Jagodzinski, F. B., Stupak, D. P., Sugrue, M. M., and Tatton, N. A. (2000) Glyceraldehyde-3-phosphate dehydrogenase in neurodegeneration and apoptosis signaling, J. Neural Transm. Suppl., 60, 77–100.

    Google Scholar 

  12. Cardon, J. W., and Boyer, P. D. (1982) Subunit interaction in catalysis. Some experimental and theoretical approaches with glyceraldehyde-3-phosphate dehydrogenase, J. Biol. Chem., 257, 7615–7622.

    CAS  PubMed  Google Scholar 

  13. Koshland, D. E. (1977) The specificity of subunit interactions, Biochem. Soc. Trans., 5, 605–606.

    Article  PubMed  Google Scholar 

  14. Malhotra, O. P., and Bernhard, S. A. (1973) Activation of a covalent enzyme—substrate bond by noncovalent interaction with an effector, Proc. Natl. Acad. Sci. USA, 70, 2077–2081.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Byers, L. D., and Koshland, D. E. (1975) The specificity of induced conformational changes. The case of yeast glyceraldehyde-3-phosphate dehydrogenase, Biochemistry, 14, 3661–3669.

    Article  CAS  PubMed  Google Scholar 

  16. Levitzki, A., and Koshland, D. E. (1976) The role of negative cooperativity and half-of-the-sites reactivity in enzyme regulation, Curr. Top. Cell. Regul., 10, 1–40.

    Article  CAS  PubMed  Google Scholar 

  17. Nagradova, N. K., Ashmarina, L. I., Asryants, R. A., Cherednikova, T. V., Golovina, T. O., and Muronetz, V. I. (1980) Glyceraldehyde-3-phosphate dehydrogenase: the role of subunit interactions in enzyme functioning, Adv. Enzyme Regul., 19, 171–204.

    Article  CAS  PubMed  Google Scholar 

  18. Nagradova, N. K. (2001) Interdomain interactions in oligomeric enzymes: creation of asymmetry in homooligomers and role in metabolite channeling between active centers of hetero-oligomers, FEBS Lett., 487, 327–332.

    Article  CAS  PubMed  Google Scholar 

  19. Nagradova, N. K. (2001) Study of the properties of phosphorylating D-glyceraldehyde-3-phosphate dehydrogenase, Biochemistry (Moscow), 66, 1067–1076.

    Article  CAS  Google Scholar 

  20. Asryants, R. A., Kuzminskaya, E. V., Tishkov, V. I., Douzhenkova, I. V., and Nagradova, N. K. (1989) An examination of the role of arginine residues in the functioning of D-glyceraldehyde-3-phosphate dehydrogenase, Biochim. Biophys. Acta, 997, 159–166.

    Article  CAS  PubMed  Google Scholar 

  21. Levashov, P. A., Schmalhausen, E. V., Muronetz, V. I., and Nagradova, N. K. (1995) E. coli D-glyceraldehyde-3-phosphate dehydrogenase modified by 2,3-butanedione: manifestation of a pairwise of non-equivalence of active centers, Biochem. Mol. Biol. Int., 37, 991–1000.

    CAS  PubMed  Google Scholar 

  22. Nagradova, N. K., Schmalhausen, E. V., Levashov, P. A., Asryants, R. A., and Muronetz, V. I. (1996) D-glyceraldehyde-3-phosphate dehydrogenase. Properties of the enzyme modified at arginine residues, Appl. Biochem. Biotechnol., 61, 47–56.

    Article  CAS  PubMed  Google Scholar 

  23. Nagradova, N. K., Asryants, R. A., and Ivanov, M. V. (1971) Interaction of 1-anilino-8-naphthalene sulfonate with yeast glyceraldehyde-3-phosphate dehydrogenase, Experientia, 27, 1169–1170.

    Article  CAS  PubMed  Google Scholar 

  24. Nagradova, N. K., Asryants, R. A., and Ivanov, M. V. (1972) 1-Anilino-8-naphthalene sulfonate as a coenzyme-competitive inhibitor of yeast glyceraldehyde-3-phosphate dehydrogenase: multiple inhibition studies, Biochim. Biophys. Acta, 268, 622–628.

    Article  CAS  PubMed  Google Scholar 

  25. Golovina, T. O., Muronetz, V. I., and Nagradova, N. K. (1978) Half-of-the-sites reactivity of rat skeletal muscle D-glyceraldehyde-3-phosphate dehydrogenase, Biochim. Biophys. Acta, 524, 15–25.

    Article  CAS  PubMed  Google Scholar 

  26. Muronets, V. I., Golovina, T. O., and Nagradova, N. K. (1982) Use of immobilization for the study of glyceraldehyde 3-phosphate dehydrogenase. Immobilized dimers of the enzyme, Biochemistry (Moscow), 47, 3–12.

    CAS  Google Scholar 

  27. Soukri, A., Mougin, A., Corbier, C., Wonacott, A., Branlant, C., and Branlant, G. (1989) Role of the histidine 176 residue in glyceraldehyde-3-phosphate dehydrogenase as probed by site-directed mutagenesis, Biochemistry, 28, 2586–2592.

    Article  CAS  PubMed  Google Scholar 

  28. Clermont, S., Corbier, C., Mely, Y., Gerard, D., Wonacott, A., and Branlant, G. (1993) Determinants of coenzyme specificity in glyceraldehyde-3-phosphate dehydrogenase: role of the acidic residue in the fingerprint region of the nucleotide binding fold, Biochemistry, 32, 10178–10184.

    Article  CAS  PubMed  Google Scholar 

  29. Little, C., and O’Brien, P. J. (1969) Mechanism of peroxide-inactivation of the sulphydryl enzyme glyceraldehyde-3-phosphate dehydrogenase, Eur. J. Biochem., 10, 533–538.

    Article  CAS  PubMed  Google Scholar 

  30. Muronetz, V. I., Melnikova, A. K., Saso, L., and Schmalhausen, E. V. (2018) Influence of oxidative stress on catalytic and non-glycolytic functions of glyceraldehyde-3-phosphate dehydrogenase, Curr. Med. Chem., doi: https://doi.org/10.2174/0929867325666180530101057.

  31. You, K. S., Benitez, L. V., McConachie, W. A., and Allison, W. S. (1975) The conversion of glyceraldehyde-3-phosphate dehydrogenase to an acylphosphatase by trinitroglycerin and inactivation of this activity by azide and ascorbate, Biochim. Biophys. Acta, 384, 317–330.

    Article  CAS  Google Scholar 

  32. Peralta, D., Bronowska, A. K., Morgan, B., Doka, E., Van Laer, K., Nagy, P., Grater, F., and Dick, T P. (2015) A proton relay enhances H2O2 sensitivity of GAPDH to facilitate metabolic adaptation, Nat. Chem. Biol., 11, 156–163.

    Article  CAS  PubMed  Google Scholar 

  33. Leichert, L. I., Gehrke, F., Gudiseva, H. V., Blackwell, T., Ilbert, M., Walker, A. K., Strahler, J. R., Andrews, P. C., and Jakob, U. (2008) Quantifying changes in the thiol redox proteome upon oxidative stress in vivo, Proc. Natl. Acad. Sci. USA, 105, 8197–8202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Cremers, C. M., and Jakob, U. (2013) Oxidant sensing by reversible disulfide bond formation, J. Biol. Chem., 288, 26489–26496.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Roos, G., and Messens, J. (2011) Protein sulfenic acid formation: from cellular damage to redox regulation, Free Radic. Biol. Med., 51, 314–326.

    Article  CAS  PubMed  Google Scholar 

  36. Rehder, D. S., and Borges, C. R. (2010) Cysteine sulfenic acid as an intermediate in disulfide bond formation and nonenzymatic protein folding, Biochemistry, 49, 7748–7755.

    Article  CAS  PubMed  Google Scholar 

  37. Bedhomme, M., Adamo, M., Marchand, C. H., Couturier, J., Rouhier, N., Lemaire, S. D., Zaffagnini, M., and Trost, P. (2012) Glutathionylation of cytosolic glyceraldehyde-3-phosphate dehydrogenase from the model plant Arabidopsis thaliana is reversed by both glutaredoxins and thioredoxins in vitro, Biochem. J., 445, 337–347.

    Article  CAS  PubMed  Google Scholar 

  38. Barinova, K. V., Serebryakova, M. V., Muronetz, V. I., and Schmalhausen, E. V. (2017) S-glutathionylation of glyceraldehyde-3-phosphate dehydrogenase induces formation of C150—C154 intrasubunit disulfide bond in the active site of the enzyme, Biochim. Biophys. Acta, 1861, 3167–3177.

    Article  CAS  Google Scholar 

  39. Gao, X. H., Bedhomme, M., Veyel, D., Zaffagnini, M., and Lemaire, S. D. (2009) Methods for analysis of protein glutathionylation and their application to photosynthetic organisms, Mol. Plant, 2, 218–235.

    Article  CAS  PubMed  Google Scholar 

  40. Newman, S. F., Sultana, R., Perluigi, M., Coccia, R., Cai, J., Pierce, W. M., Klein, J. B., Turner, D. M., and Butterfield, D. A. (2007) An increase in S-glutathionylated proteins in the Alzheimer’s disease inferior parietal lobule, a proteomics approach, J. Neurosci. Res., 85, 1506–1514.

    Article  CAS  PubMed  Google Scholar 

  41. Schuppe-Koistinen, I., Moldeus, P., Bergman, T., and Cotgreave, I. A. (1994) S-thiolation of human endothelial cell glyceraldehyde-3-phosphate dehydrogenase after hydrogen peroxide treatment, Eur. J. Biochem., 221, 1033–1037.

    Article  CAS  PubMed  Google Scholar 

  42. Davies, M. J. (2016) Protein oxidation and peroxidation, Biochem. J., 473, 805–825.

    Article  CAS  PubMed  Google Scholar 

  43. Elkina, Y. L., Kuravsky, M. L., El’darov, M. A., Stogov, S. V., Muronetz, V. I., and Schmalhausen, E. V. (2010) Recombinant human sperm-specific glyceraldehyde-3-phosphate dehydrogenase: structural basis for enhanced stability, Biochim. Biophys. Acta, 1804, 2207–2212.

    Article  CAS  PubMed  Google Scholar 

  44. Baty, J. W., Hampton, M. B., and Winterbourn, C. C. (2005) Proteomic detection of hydrogen peroxide-sensitive thiol proteins in Jurkat cells, Biochem. J., 389, 785–795.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Aronov, A. M., Verlinde, C. L., Hol, W. G., and Gelb, M. H. (1998) Selective tight binding inhibitors of trypanosomal glyceraldehyde-3-phosphate dehydrogenase via structure-based drug design, J. Med. Chem., 41, 4790–4799.

    Article  CAS  PubMed  Google Scholar 

  46. Ladame, S., Bardet, M., Perie, J., and Willson, M. (2001) Selective inhibition of Trypanosoma brucei GAPDH by 1,3-bisphospho-D-glyceric acid (1,3-diPG) analogues, Bioorg. Med. Chem., 9, 773–783.

    Article  CAS  PubMed  Google Scholar 

  47. Callens, M., and Hannaert, V. (1995) The rational design of trypanocidal drugs: selective inhibition of the glyceraldehyde-3-phosphate dehydrogenase in Trypanosomatidae, Ann. Trop. Med. Parasitol., 89(Suppl. 1), 23–30.

    Article  CAS  PubMed  Google Scholar 

  48. Haanstra, J. R., Gerding, A., Dolga, A. M., Sorgdrager, F. J. H., Buist-Homan, M., du Toit, F., Faber, K. N., Holzhutter, H. G., Szoor, B., Matthews, K. R., Snoep, J. L., Westerhoff, H. V., and Bakker, B. M. (2017) Targeting pathogen metabolism without collateral damage to the host, Sci. Rep., 7, 40406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Pereira, J. M., Severino, R. P., Vieira, P. C., Fernandes, J. B., da Silva, M. F. G. F., Zottis, A., Andricopulo, A. D., Oliva, G., and Correa, A. G. (2008) Anacardic acid derivatives as inhibitors of glyceraldehyde-3-phosphate dehydrogenase from Trypanosoma cruzi, Bioor. Med. Chem., 16, 8889–8895.

    Article  CAS  Google Scholar 

  50. Prokopczyk, I. M., Ribeiro, J. F. R., Sartori, G. R., Sesti-Costa, R., Silva, J. S., Freitas, R. F., Leitao, A., and Montanari, C. A. (2014) Integration of methods in cheminformatics and biocalorimetry for the design of trypanosomatid enzyme inhibitors, Future Med. Chem., 6, 17–33.

    Article  CAS  PubMed  Google Scholar 

  51. Chu, H., Puchulu-Campanella, E., Galan, J. A., Tao, W. A., Low, P. S., and Hoffman, J. F. (2012) Identification of cytoskeletal elements enclosing the ATP pools that fuel human red blood cell membrane cation pumps, Proc. Natl. Acad. Sci. USA, 109, 12794–12799.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Muronetz, V. I., and Nagradova, N. K. (1990) Interaction of glyceraldehyde-3-phosphate dehydrogenase with structural elements of cells, Usp. Biol. Khim., 31, 115–131.

    Google Scholar 

  53. Opperdoes, F. R., and Borst, P. (1977) Localization of nine glycolytic enzymes in a microbody-like organelle in Trypanosoma brucei: the glycosome, FEBS Lett., 80, 360–364.

    Article  CAS  PubMed  Google Scholar 

  54. Van Calenbergh, S., Verlinde, C. L., Soenens, J., De Bruyn, A., Callens, M., Blaton, N. M., Peeters, O. M., Herdewijn, P., Rozenski, J., and Hol, W. G. J. (1995) Synthesis and structure-activity relationships of analogs of 2′-deoxy-2′-(3-methoxybenzamido)adenosine, a selective inhibitor of trypanosomal glycosomal glyceraldehyde-3-phosphate dehydrogenase, J. Med. Chem., 38, 3838–3849.

    Article  CAS  PubMed  Google Scholar 

  55. Link, A., Heidler, P., Kaiser, M., and Brun, R. (2009) Synthesis of a series of N6-substituted adenosines with activity against trypanosomatid parasites, Eur. J. Med. Chem., 44, 3665–3671.

    Article  CAS  PubMed  Google Scholar 

  56. Herrmann, F. C., Lenz, M., Jose, J., Kaiser, M., Brun, R., and Schmidt, T. J. (2015) In silico identification and in vitro activity of novel natural inhibitors of Trypanosoma brucei glyceraldehyde-3-phosphate-dehydrogenase, Molecules, 20, 16154–16169.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Uliassi, E., Fiorani, G., Krauth-Siegel, R. L., Bergamini, C., Fato, R., Bianchini, G., Carlos Menendez, J., Molina, M. T., Lopez-Montero, E., Falchi, F., Cavalli, A., Gul, S., Kuzikov, M., Ellinger, B., Witt, G., Moraes, C. B., Freitas-Junior, L. H., Borsari, C., Costi, M. P., and Bolognesi, M. L. (2017) Crassiflorone derivatives that inhibit Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH) and Trypanosoma cruzi trypanothione reductase (TcTR) and display trypanocidal activity, Eur. J. Med. Chem., 141, 138–148.

    Article  CAS  PubMed  Google Scholar 

  58. Vinhote, J. F. C., Lima, D. B., Menezes, R. R. P. P. B., Mello, C. P., de Souza, B. M., Havt, A., Palma, M. S., Santos, R. P. D., Albuquerque, E. L., Freire, V. N., and Martins, A. M. C. (2017) Trypanocidal activity of mastoparan from Polybia paulista wasp venom by interaction with TcGAPDH, Toxicon, 137, 168–172.

    Article  CAS  PubMed  Google Scholar 

  59. Belluti, F., Uliassi, E., Veronesi, G., Bergamini, C., Kaiser, M., Brun, R., Viola, A., Fato, R., Michels, P. A., Krauth-Siegel, R. L., Cavalli, A., and Bolognesi, M. L. (2014) Toward the development of dual-targeted glyceraldehyde-3-phosphate dehydrogenase/trypanothione reductase inhibitors against Trypanosoma brucei and Trypanosoma cruzi, ChemMedChem., 9, 371–382.

    Article  CAS  PubMed  Google Scholar 

  60. Miki, K., Qu, W., Goulding, E. H., Willis, W. D., Bunch, D. O., Strader, L. F., Perreault, S. D., Eddy, E. M., and O’Brien, D. A. (2004) Glyceraldehyde 3-phosphate dehydrogenase-S, a sperm-specific glycolytic enzyme, is required for sperm motility and male fertility, Proc. Natl. Acad. Sci. USA, 101, 16501–16506.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Lamson, D. R., House, A. J., Danshina, P. V., Sexton, J. Z., Sanyang, K., O’Brien, D. A., Yeh, L. A., and Williams, K. P. (2011) Recombinant human sperm-specific glyceraldehyde-3-phosphate dehydrogenase (GAPDHS) is expressed at high yield as an active homotetramer in baculovirus-infected insect cells, Protein Expr. Purif., 75, 104–113.

    Article  CAS  PubMed  Google Scholar 

  62. Chaikuad, A., Shafqat, N., Al-Mokhtar, R., Cameron, G., Clarke, A. R., Brady, R. L., Oppermann, U., Frayne, J., and Yue, W. W. (2011) Structure and kinetic characterization of human sperm-specific glyceraldehyde-3-phosphate dehydrogenase, GAPDS, Biochem. J., 435, 401–409.

    Article  CAS  PubMed  Google Scholar 

  63. Kuravsky, M., Barinova, K., Marakhovskaya, A., Eldarov, M., Semenyuk, P., Muronetz, V., and Schmalhausen, E. (2014) Sperm-specific glyceraldehyde-3-phosphate dehydrogenase is stabilized by additional proline residues and an interdomain salt bridge, Biochim. Biophys. Acta, 1844, 1820–1826.

    Article  CAS  PubMed  Google Scholar 

  64. Kuravsky, M. L., Barinova, K. V., Asryants, R. A., Schmalhausen, E. V., and Muronetz, V. I. (2015) Structural basis for the NAD binding cooperativity and catalytic characteristics of sperm-specific glyceraldehyde-3-phosphate dehydrogenase, Biochimie, 115, 28–34.

    Article  CAS  PubMed  Google Scholar 

  65. Frayne, J., Taylor, A., Cameron, G., and Hadfield, A. T. (2009) Structure of insoluble rat sperm glyceraldehyde-3-phosphate dehydrogenase (GAPDH) via heterotetramer formation with Escherichia coli GAPDH reveals target for contraceptive design, J. Biol. Chem., 284, 22703–227012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Dan’shina, P. V., Qu, W., Temple, B. R., Rojas, R. J., Miley, M. J., Machius, M., Betts, L., and O’Brien, D. A. (2016) Structural analyses to identify selective inhibitors of glyceraldehyde 3-phosphate dehydrogenase-S, a sperm-specific glycolytic enzyme, Mol. Hum. Reprod., 22, 410–426.

    Article  CAS  Google Scholar 

  67. Sexton, J. Z., Danshina, P. V., Lamson, D. R., Hughes, M., House, A. J., Yeh, L. A., O’Brien, D. A., and Williams, K. P. (2011) Development and implementation of a high throughput screen for the human sperm-specific isoform of glyceraldehyde 3-phosphate dehydrogenase (GAPDHS), Curr. Chem. Genomics, 5, 30–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Sevostyanova, I. A., Kulikova, K. V., Kuravsky, M. L., Schmalhausen, E. V., and Muronetz, V. I. (2012) Sperm-specific glyceraldehyde-3-phosphate dehydrogenase is expressed in melanoma cells, Biochem. Biophys. Res. Commun., 427, 649–653.

    Article  CAS  PubMed  Google Scholar 

  69. Boradia, V. M., Malhotra, H., Thakkar, J. S., Tillu, V. A., Vuppala, B., Patil, P., Sheokand, N., Sharma, P., Chauhan, A. S., Raje, M., and Raje, C. I. (2014) Mycobacterium tuberculosis acquires iron by cell-surface sequestration and internalization of human holo-transferrin, Nat. Commun., 5, 4730.

    Article  CAS  PubMed  Google Scholar 

  70. Andries, K., Verhasselt, P., Guillemont, J., Gohlmann, H. W. H., Neefs, J.-M., Winkler, H., Van Gestel, J., Timmerman, P., Zhu, M., Lee, E., Williams, P., de Chaffoy, D., Huitric, E., Hoffner, S., Cambau, E., Truffot-Pernot, C., Lounis, N., and Jarlier, V. (2005) A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis, Science, 307, 223–227.

    Article  CAS  PubMed  Google Scholar 

  71. Koul, A., Vranckx, L., Dendouga, N., Balemans, W., Van den Wyngaert, I., Vergauwen, K., Gohlmann, H. W., Willebrords, R., Poncelet, A., Guillemont, J., Bald, D., and Andries, K. (2008) Diarylquinolines are bactericidal for dormant mycobacteria as a result of disturbed ATP homeostasis, J. Biol. Chem., 283, 25273–25280.

    Article  CAS  PubMed  Google Scholar 

  72. Pethe, K., Bifani, P., Jang, J., Kang, S., Park, S., et al. (2013) Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis, Nat. Med., 19, 1157–1160.

    Article  CAS  PubMed  Google Scholar 

  73. Forte, E., Borisov, V. B., Falabella, M., Colaco, H. G., Tinajero-Trejo, M., Poole, R. K., Vicente, J. B., Sarti, P., and Giuffre, A. (2016) The terminal oxidase cytochrome bd promotes sulfide-resistant bacterial respiration and growth, Sci. Rep., 6, 23788.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Forte, E., Borisov, V. B., Vicente, J. B., and Giuffre, A. (2017) Cytochrome bd and gaseous ligands in bacterial physiology, Adv. Microb. Physiol., 71, 171–234.

    Article  PubMed  Google Scholar 

  75. Malhotra, O. P., and Bernhard, S. A. (1981) Role of nicotinamide adenine dinucleotide as an effector in formation and reactions of acylglyceraldehyde-3-phosphate dehydrogenase, Biochemistry, 20, 5529–5538.

    Article  CAS  PubMed  Google Scholar 

  76. Muronetz, V. I., Melnikova, A. K., Seferbekova, Z. N., Barinova, K. V., and Schmalhausen, E. V. (2017) Glycation, glycolysis, and neurodegenerative diseases: is there any connection? Biochemistry (Moscow), 82, 874–886.

    Article  CAS  Google Scholar 

  77. Lee, H. J., Howell, S. K., Sanford, R. J., and Beisswenger, P. J. (2005) Methylglyoxal can modify GAPDH activity and structure, Ann. NY Acad. Sci., 1043, 135–145.

    Article  CAS  PubMed  Google Scholar 

  78. Muronetz, V., Barinova, K., and Schmalhausen, E. (2017) Glycation of glyceraldehyde-3-phosphate dehydrogenase in the presence of glucose and glyceraldehyde-3-phosphate, J. Int. Soc. Antioxid., 2, 1–4.

    Google Scholar 

  79. Cornish-Bowden, A. (1981) Thermodynamic aspects of glycolysis, Biochem. Educ., 9, 133–137.

    Article  CAS  Google Scholar 

  80. Veech, R. L., Raijman, L., Dalziel, K., and Krebs, H. A. (1969) Disequilibrium in the triose phosphate isomerase system in rat liver, Biochem. J., 115, 837–842.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

The work was supported by the Russian Science Foundation (grant no. 16-14-10027).

Author information

Authors and Affiliations

  1. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119234, Moscow, Russia

    V. I. Muronetz, K. V. Barinova & E. V. Schmalhausen

  2. Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119234, Moscow, Russia

    V. I. Muronetz & A. K. Melnikova

Authors
  1. V. I. Muronetz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. K. Melnikova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. V. Barinova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. V. Schmalhausen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. I. Muronetz.

Additional information

Conflict of interest

The authors declare no conflict of interest.

Compliance with ethical standards

This article does not contain any research using animals or people performed by any of the authors.

Published in Russian in Biokhimiya, 2019, Vol. 84, No. 11, pp. 1578–1591.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Muronetz, V.I., Melnikova, A.K., Barinova, K.V. et al. Inhibitors of Glyceraldehyde 3-Phosphate Dehydrogenase and Unexpected Effects of Its Reduced Activity. Biochemistry Moscow 84, 1268–1279 (2019). https://doi.org/10.1134/S0006297919110051

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297919110051

Keywords

Search

Navigation