Polyol pathway
The polyol pathway is a two-step process that converts glucose to fructose.[1] In this pathway glucose is reduced to sorbitol, which is subsequently oxidized to fructose. It is also called the sorbitol-aldose reductase pathway.
The pathway is implicated in
nerves.[4]
Sorbitol cannot cross
osmotic stresses on cells by drawing water into the insulin-independent tissues.[5]
Pathway
Cells use
blood glucose - more than the glycolysis pathway can handle - the reactions mass balance ultimately favors the production of sorbitol.[6]
Activation of the polyol pathway results in a decrease of reduced NADPH and oxidized NAD+; these are necessary co-factors in
advanced glycation end-products. AGEs are thought to cause disease in the human body, one effect of which is mediated by RAGE (receptor for advanced glycation end-products) and the ensuing inflammatory responses induced. They are seen in the hemoglobin A1C tests performed on known diabetics to assess their levels of glucose control.[6]
Pathology
While most cells require the action of
concentrations.[citation needed
]
In a hyperglycemic state, the affinity of aldose reductase for glucose rises, causing much sorbitol to accumulate, and using much more
cellular metabolism.[7]
This change of affinity is what is meant by activation of the pathway. The amount of sorbitol that accumulates, however, may not be sufficient to cause osmotic influx of water.
NADPH acts to promote
vasodilators in blood vessels. Therefore, NADPH prevents reactive oxygen species from accumulating and damaging cells.[6]
Excessive activation of the polyol pathway increases
extracellular sorbitol concentrations, increased concentrations of reactive oxygen species, and decreased concentrations of nitric oxide and glutathione. Each of these imbalances can damage cells; in diabetes there are several acting together. It has not been conclusively determined that activating the polyol pathway damages the microvascular systems.[6]
References
Further references
- Harper's Illustrated Biochemistry(Published by LANGE)
- Dinesh Puri's Medical Biochemistry(Published by ELSEVIER)