Understanding Diabetic Neuropathy: Focus on Oxidative Stress

Figure 2

Major glucose metabolism pathway under physiological condition and diabetic condition. (a) Under a physiological condition, intracellular glucose is converted to glucose-6-phosphate, via hexokinase, then following isomerization to fructose-6-phosphate. Along glycolysis pathway, glyceraldehyde-3-phosphate travels down to pyruvate and acetyl CoA via pyruvate dehydrogenase, which then enters tricarboxylic acid (TCA) cycle. NADH, as electron carrier and generated during the process of glycolysis and glucose oxidation, can donate reducing equivalents to the mitochondrial electron transport chain (ETC), thereby creating a proton gradient that is used by ATP synthase to produce ATP and converting O₂ to H₂O. (b) Under diabetic condition, glucose metabolism is impaired, causing accumulation of glucose and the glycolytic intermediates, resulting mitochondrial injury, thereby converting O₂ to superoxide radical (O₂^•−) instead of H₂O. As a result, ATP production is reduced.