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

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V. I. Muronetz^1,2,a*, A. K. Melnikova², K. V. Barinova¹, and E. V. Schmalhausen¹

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

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

^* To whom correspondence should be addressed.

Received June 11, 2019; Revised August 11, 2019; Accepted August 14, 2019

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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.).

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KEY WORDS: glyceraldehyde 3-phosphate dehydrogenase, inhibitors, oxidation, sulfhydryl group, glycation, glycolysis

DOI: 10.1134/S0006297919110051

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