When glucose is unused, it is metabolized via the polyol pathway. This pathway consists of two main enzymatic steps. First, glucose is reduced to sorbitol by aldose reductase. In this step, NADPH is oxidized to NADP+. The next step is the oxidation of sorbitol to D-fructose by sorbitol dehydrogenase. Fructose can then be phosphorylated by fructokinase and subsequently be metabolized via dihydroxyacetone phosphate or glyceraldehyde to D-glyceraldehyde 3-phosphate, which can be used as a substrate in the process of glycolysis. The sorbitol pathway plays a role in diabetic renal complications because aldose reductase metabolizes the excess of glucose to toxic metabolites that induce hyperfiltration and glomerular dysfunction. ccc e59 f60 Main reaction product dehydration reaction dehydration reaction Main reaction dehydration reaction dehydration reaction Diabetes DOID:9351 Human Disease Ontology renal disease, renal disorder pathway PW:0000300 Pathway Ontology glucose utilization pathway PW:0000555 Pathway Ontology polyol pathway PW:0001520 Pathway Ontology glucose oxidation pathway PW:0000556 Pathway Ontology 10997684 PubMed Aldose reductase and the role of the polyol pathway in diabetic nephropathy. Kidney Int Suppl 2000 Dunlop M 8535439 PubMed Molecular basis of hereditary fructose intolerance: mutations and polymorphisms in the human aldolase B gene. Hum Mutat 1995 Tolan DR 11742414 PubMed Biochemistry and molecular cell biology of diabetic complications. Nature 2001 Brownlee M