Polyol pathway (WP690)
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.
AuthorsPieter Giesbertz , Kristina Hanspers , Daniela Digles , Alex Pico , Martina Summer-Kutmon , Friederike Ehrhart , Denise Slenter , Egon Willighagen , and Eric Weitz
Discuss this pathway
- Proteostasis regulators modulate proteasomal activity and gene expression to attenuate multiple phenotypes in Fabry disease (2020).
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OrganismsHomo sapiens Renal Genomics Pathways
Disease Ontologydiabetes mellitus
Pathway Ontologykidney disease pathway glucose utilization pathway polyol pathway glucose oxidation pathway
|Main reaction product
- Molecular basis of hereditary fructose intolerance: mutations and polymorphisms in the human aldolase B gene. Tolan DR. Hum Mutat. 1995;6(3):210–8. PubMed Europe PMC Scholia
- Aldose reductase and the role of the polyol pathway in diabetic nephropathy. Dunlop M. Kidney Int Suppl. 2000 Sep;77:S3-12. PubMed Europe PMC Scholia
- Biochemistry and molecular cell biology of diabetic complications. Brownlee M. Nature. 2001 Dec 13;414(6865):813–20. PubMed Europe PMC Scholia