Contribution of the toxic advanced glycation end-products-receptor axis in nonalcoholic steatohepatitis-related hepatocellular carcinoma

Figure 2 In vivo production routes of glycer-advanced glycation end-products (toxic advanced glycation end-products). The chronic and excessive ingestion of sugar-sweetened beverages (HFCS/sucrose) increases the levels of the sugar metabolite, glyceraldehyde in the liver. The glycolytic intermediate glyceraldehyde-3-phosphate (G-3-P) is normally catabolized (glycolysis) by the enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). G-3-P accumulates intracellularly with a decline in GAPDH activity. The metabolism of G-3-P then shifts to another route, resulting in an increase in the amount of glyceraldehyde, which promotes the formation of glycer-advanced glycation end-products (AGEs) (TAGE). Fructose from the daily diet and polyol pathway is phosphorylated to fructose-1-phosphate (F-1-P) by fructokinase and is then catabolized to glyceraldehyde and dihydroxyacetone phosphate by aldolase B (fructolysis). The newly synthesized glyceraldehyde is then transported or leaks passively across the plasma membrane. Glyceraldehyde promotes the formation of TAGE both intracellularly and extracellularly. DHA-P: Dihydroxyacetone-phosphate; FK: Fructokinase; HFCS: High-fructose corn syrup; TAGE: Toxic advanced glycation end-products; TG: Triglyceride; Protein-NH2: Free amino residue of a protein.