Figure 12

Overview of methylglyoxal (MG)formation via glycolysis and the degradation of the methylglyoxal-glutathione hemiacetal in uninfected and SARS-CoV-2 infected individuals. MG is formed from the interconversion of the dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P) via triosephosphate isomerase that generates MG. MG is detoxified by the dual-enzyme glyoxalase system. In the first step, the rate-limiting glyoxalase 1 (Glo1) converts the hemithioacetal formed between MG and reduced glutathione (MG-GSH) to the thioester S-d-lactoylglutathione. In the second step glyoxalase 2 (Glo2) enzyme catalyzes the hydrolysis of S-d-lactoylglutathione to form d-lactate. During this reaction, GSH is recycled. Following SARS-CoV-2 infection, glycolysis is upregulated in the infected cells and host immune cells. At the same time, Glo1 and GSH are down regulated, resulting in cytotoxic levels of MG.