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.
last edited

Authors

Pieter Giesbertz, MaintBot, Khanspers, Ddigles, AlexanderPico, Mkutmon, Fehrhart, DeSl, Egonw, and Eweitz

Cited In

Organism

Homo sapiens

Communities

Renal Genomics Pathways

Annotations

Disease Ontology: diabetes mellitus

Pathway Ontology: kidney disease pathway glucose utilization pathway polyol pathway glucose oxidation pathway

Participants

Label Type Compact Identifier
D-Sorbitol Metabolite hmdb:HMDB0000247
D-Glucose Metabolite hmdb:HMDB0000122
Fructokinase GeneProduct ensembl:ENSG00000138030
D-Fructose Metabolite hmdb:HMDB0000660
ALDOB GeneProduct ensembl:ENSG00000136872
Dihydroxyacetone phosphate Metabolite hmdb:HMDB0001473
Glyceraldehyde Metabolite hmdb:HMDB0001051
ALR2 GeneProduct ncbigene:231
1,5-anhydrosorbitol Metabolite wikidata:Q4545703
Fructose 1-phosphate Metabolite hmdb:HMDB0001076
Glycolysis Pathway wikipathways:WP534
SORD GeneProduct ensembl:ENSG00000140263
D-Glyceraldehyde 3-phosphate Metabolite hmdb:HMDB0001112
Glycolysis Pathway wikipathways:WP534
1,4-anhydrosorbitol Metabolite pubchem.compound:10953859
1,4,3,6-dianhydrosorbitol Metabolite chemspider:16739231
Isosorbid Metabolite wikidata:Q1243800

References

  1. Tolan DR. Molecular basis of hereditary fructose intolerance: mutations and polymorphisms in the human aldolase B gene. Hum Mutat. 1995;6(3):210–8. PubMed Europe PMC Scholia
  2. Dunlop M. Aldose reductase and the role of the polyol pathway in diabetic nephropathy. Kidney Int Suppl. 2000 Sep;77:S3-12. PubMed Europe PMC Scholia
  3. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001 Dec 13;414(6865):813–20. PubMed Europe PMC Scholia