Sandbox Reserved 339: Difference between revisions
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==Introduction== | ==Introduction== | ||
<scene name='Sandbox_Reserved_339/Default_scene/1'>Aldose reductase</scene> is an oxidoreductase/dehydrogenase enzyme.<ref name="wikipedia"> Wikipedia. Aldose Reductase. http://en.wikipedia.org/wiki/Aldose_reductase </ref> Aldose reductase can reduce the aldehyde group of aldoses, aliphatic, aromatic aldehydes and some keto groups from aromatic and aliphatic ketones to their corresponding alcohol products using NADPH as a cofactor.<ref name="Steuber"> PMID 17368668 </ref><ref name="review"> PMID 15094999 </ref> Aldose reductase is most well known in the first step of the polyol pathway of glucose metabolism.<ref name="Steuber"/><ref name="review"/> | <scene name='Sandbox_Reserved_339/Default_scene/1'>Aldose reductase</scene> is an oxidoreductase/dehydrogenase enzyme.<ref name="wikipedia"> Wikipedia. Aldose Reductase. http://en.wikipedia.org/wiki/Aldose_reductase </ref> Aldose reductase can reduce the aldehyde group of aldoses, aliphatic, aromatic aldehydes and some keto groups from aromatic and aliphatic ketones to their corresponding alcohol products using NADPH as a cofactor.<ref name="Steuber"> PMID 17368668 </ref><ref name="review"> PMID 15094999 </ref> Aldose reductase is most well known in the first step of the polyol pathway of glucose metabolism.<ref name="Steuber"/><ref name="review"/> | ||
[[Image:Polyol_pathway.jpg|left|400px|thumb|Figure 1. Polyol pathway of glucose metabolism. Adapted from Petrash JM. All in the family: aldose reductase and closely related aldo-keto reductases. Cell Mol Life Sci. 2004 Apr;61(7-8):737-49. PMID:15094999 doi:10.1007/s00018-003-3402-3]] | |||
==Polyol Pathway and Diabetes== | ==Polyol Pathway and Diabetes== | ||
The polyol pathway involves the synthesis of fructose from glucose, but does not require energy from ATP like glycolysis does.<ref name="Steuber"/><ref name="review"/><ref name="wikipedia"/> The first step of the pathway is the production of sorbitol from glucose, catalyzed by aldose reductase and using NADPH as a reducing cofactor.<ref name="Steuber"/><ref name="review"/> The second step in the pathway is the production of fructose from sorbitol, catalyzed by sorbitol dehydrogenase using NAD+.<ref name="Steuber"/><ref name="review"/> Under normal blood glucose levels most glucose is metabolized through glycolysis or the pentose phosphate pathway while only a small amount of glucose is metabolized through the polyol pathway.<ref name="review"/> Under the hyperglycemic conditions of diabetes the flux of glucose through the polyol pathway is increased.<ref name="Steuber"/><ref name="review"/> This causes osmotic and oxidative stress, which can cause pathological interferences with cytokine signalling, regulation of apoptosis, and activation of kinase cascades.<ref name="Steuber"/> For example, under increased glucose flux through the polyol pathway protein kinase C activivty increases, which causes smooth muscle cell proliferation of blood vessels in agreement with atherosclerosis.<ref name="Steuber"/> This explains estimates that 75-80% of adults with diabetes die from complications of atherosclerosis.<ref name="Steuber"/> Aldose reductase is located in the cornea, retina, lens, kidneys, and myelin sheath.<ref name="wikipedia"/> This correlates with long-term complications such as retinopathy, nephropathy, neuropathy, cataracts, and angiopathy.<ref name="Steuber"/> Aldose reductase inhibitors are possible beneficial treatment options for diabetes.<ref name="Steuber"/> | The polyol pathway involves the synthesis of fructose from glucose, but does not require energy from ATP like glycolysis does.<ref name="Steuber"/><ref name="review"/><ref name="wikipedia"/> The first step of the pathway is the production of sorbitol from glucose, catalyzed by aldose reductase and using NADPH as a reducing cofactor.<ref name="Steuber"/><ref name="review"/> The second step in the pathway is the production of fructose from sorbitol, catalyzed by sorbitol dehydrogenase using NAD+.<ref name="Steuber"/><ref name="review"/> Under normal blood glucose levels most glucose is metabolized through glycolysis or the pentose phosphate pathway while only a small amount of glucose is metabolized through the polyol pathway.<ref name="review"/> Under the hyperglycemic conditions of diabetes the flux of glucose through the polyol pathway is increased.<ref name="Steuber"/><ref name="review"/> This causes osmotic and oxidative stress, which can cause pathological interferences with cytokine signalling, regulation of apoptosis, and activation of kinase cascades.<ref name="Steuber"/> For example, under increased glucose flux through the polyol pathway protein kinase C activivty increases, which causes smooth muscle cell proliferation of blood vessels in agreement with atherosclerosis.<ref name="Steuber"/> This explains estimates that 75-80% of adults with diabetes die from complications of atherosclerosis.<ref name="Steuber"/> Aldose reductase is located in the cornea, retina, lens, kidneys, and myelin sheath.<ref name="wikipedia"/> This correlates with long-term complications such as retinopathy, nephropathy, neuropathy, cataracts, and angiopathy.<ref name="Steuber"/> Aldose reductase inhibitors are possible beneficial treatment options for diabetes.<ref name="Steuber"/> | ||
==Structure== | ==Structure== | ||