Polyol pathway (WP690)

Homo sapiens

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.


Pieter Giesbertz , Kristina Hanspers , Daniela Digles , Alex Pico , Martina Summer-Kutmon , Friederike Ehrhart , Denise Slenter , Egon Willighagen , and Eric Weitz


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Homo sapiens


Renal Genomics Pathways


Disease Ontology

diabetes mellitus

Pathway Ontology

kidney disease pathway glucose utilization pathway polyol pathway glucose oxidation pathway


Label Type Compact URI Comment
D-Sorbitol Metabolite hmdb:HMDB0000247
D-Glucose Metabolite hmdb:HMDB0000122
D-Fructose Metabolite hmdb:HMDB0000660
Dihydroxyacetone phosphate Metabolite hmdb:HMDB0001473
Glyceraldehyde Metabolite hmdb:HMDB0001051
1,5-anhydrosorbitol Metabolite wikidata:Q4545703
Fructose 1-phosphate Metabolite hmdb:HMDB0001076
D-Glyceraldehyde 3-phosphate Metabolite hmdb:HMDB0001112
1,4-anhydrosorbitol Metabolite pubchem.compound:10953859 Main reaction product
1,4,3,6-dianhydrosorbitol Metabolite chemspider:16739231
Isosorbid Metabolite wikidata:Q1243800
Fructokinase GeneProduct ensembl:ENSG00000138030
ALDOB GeneProduct ensembl:ENSG00000136872
ALR2 GeneProduct ncbigene:231
SORD GeneProduct ensembl:ENSG00000140263


  1. 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
  2. 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
  3. Biochemistry and molecular cell biology of diabetic complications. Brownlee M. Nature. 2001 Dec 13;414(6865):813–20. PubMed Europe PMC Scholia