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==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="wikipedia"/> | The polyol pathway involves the synthesis of fructose from glucose, but does not require energy from ATP like glycolysis does.<ref name="wikipedia"/> | ||
| - | <ref name="Steuber"/> 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="wikipedia"/><ref name="Steuber"/> The second step in the pathway is the production of fructose from sorbitol, catalyzed by sorbitol dehydrogenase, which is NAD+ dependent.<ref name="wikipedia"/><ref name="Steuber"/> 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="wikipedia"/> Under the hyperglycemic conditions of diabetes the flux of glucose through the polyol pathway is increased.<ref name="wikipedia"/><ref name="Steuber"/> 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"/> | + | <ref name="Steuber"/> 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="wikipedia"/><ref name="Steuber"/> The second step in the pathway is the production of fructose from sorbitol, catalyzed by sorbitol dehydrogenase, which is NAD+ dependent.<ref name="wikipedia"/><ref name="Steuber"/> 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="wikipedia"/> Under the hyperglycemic conditions of diabetes the flux of glucose through the polyol pathway is increased.<ref name="wikipedia"/><ref name="Steuber"/> 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"/> |
==References== | ==References== | ||
<references/> | <references/> | ||
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Aldose Reductase (2IKH)
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Introduction
Aldose reductase is an oxidoreductase/dehydrogenase enzyme.[1] It reduces aldehydes and carbonyl, including monosaccharides to their corresponding alcohol products using NADPH as a cofactor.[1][2] Aldose reductase is most well known in the first step of the polyol pathway of glucose metabolism.[1][2]
Sub Title
Sub Sub Title
Polyol Pathway and Diabetes
The polyol pathway involves the synthesis of fructose from glucose, but does not require energy from ATP like glycolysis does.[1] [2] The first step of the pathway is the production of sorbitol from glucose, catalyzed by aldose reductase and using NADPH as a reducing cofactor.[1][2] The second step in the pathway is the production of fructose from sorbitol, catalyzed by sorbitol dehydrogenase, which is NAD+ dependent.[1][2] 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.[1] Under the hyperglycemic conditions of diabetes the flux of glucose through the polyol pathway is increased.[1][2] This causes osmotic and oxidative stress, which can cause pathological interferences with cytokine signalling, regulation of apoptosis, and activation of kinase cascades.[2] 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.[2] This explains estimates that 75-80% of adults with diabetes die from complications of atherosclerosis.[2] Aldose reductase is located in the cornea, retina, lens, kidneys, and myelin sheath.[1] This correlates with long-term complications such as retinopathy, nephropathy, neuropathy, cataracts, and angiopathy.[2]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 Wikipedia. Aldose Reductase. http://en.wikipedia.org/wiki/Aldose_reductase
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 Steuber H, Heine A, Klebe G. Structural and thermodynamic study on aldose reductase: nitro-substituted inhibitors with strong enthalpic binding contribution. J Mol Biol. 2007 May 4;368(3):618-38. Epub 2006 Dec 15. PMID:17368668 doi:10.1016/j.jmb.2006.12.004
