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
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2000
Dunlop M
8535439
PubMed
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Hum Mutat
1995
Tolan DR
11742414
PubMed
Biochemistry and molecular cell biology of diabetic complications.
Nature
2001
Brownlee M