Polyol pathway (WP1303)

Rattus norvegicus

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.


Daniela Digles and Agustin Gonzalez-Vicente


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Rattus norvegicus


Renal Genomics Pathways


Pathway Ontology

glucose utilization pathway

Cell Type Ontology

cell epithelial cell of proximal tubule


Label Type Compact URI Comment
Sorbitol Metabolite hmdb:HMDB0000247
D-Glucose Metabolite hmdb:HMDB0000122
D-Fructose Metabolite hmdb:HMDB0000660
Dihydroxyacetone phosphate Metabolite hmdb:HMDB0001473
Glyceraldehyde Metabolite hmdb:HMDB0001051
Fructose 1-phosphate Metabolite hmdb:HMDB0001076
D-Glyceraldehyde 3-phosphate Metabolite hmdb:HMDB0001112
Khk GeneProduct ensembl:ENSRNOG00000008047
Aldob GeneProduct ensembl:ENSRNOG00000006807
Akr1b1 GeneProduct ncbigene:24192
SORD GeneProduct ncbigene:24788


  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