The contribution of unscheduled glycolysis to diabetic retinopathy. (A) represents key regulatory steps of scheduled glycolysis, while (B) represents hyperglycemia-linked glycolytic overload and metabolic dysfunction in unscheduled glycolysis resulting from activation of the polyol, hexosamine, PKC, and AGEs pathways, which further cause oxidative stress and inflammation leading to retinal cell dysfunction. Yellow arrows depict metabolic dysfunction in unscheduled glycolysis. Abbreviations: Glucose-6-P, glucose-6-phosphate; Fructose-6-P, fructose-6-phosphate; Fructose 1,6-bis-P, fructose 1,6-bis-Phosphate; GA-3-P, glyceraldehyde-3-phosphate; DHAP, dihydroxyacetone phosphate; 1,3 bis PG, 1,3 diphosphoglycerate; 3-PG, 3-phosphoglycerate; 2-PG; 2-phosphoglycerate; PEP, phosphoenolpyruvate; HK, hexokinase; G6PI, glucose 6-phosphate isomerase; PFK, phosphofructokinase; TPI, triose phosphate isomerase; Aldo, aldolase; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; PGK, phosphoglycerate kinase; PGM, phosphoglycerate mutase; PK, pyruvate kinase; L-LD, L-lactic dehydrogenase; HK2, hexokinase2; OS, osmotic stress; AR, aldolase reductase; SDH, sorbitol dehydrogenase; GlucN-6-P, glucosamine-6-P; UDP-GlcNAc, uridine diphosphate-N-acetylhexosamine; GFAT, glutamine fructose-6-P amidotransferase; Gln, glutamine; Glu, glutamate; G3P, glycerol-3-P; PKC, protein kinase C; MG, methylglycoxal; MGS, methylglycoxal synthase AGE, advance glycation end-products. The figure is adopted with modification from [43].