Category: catabolism
Alternative glucose pathway active in tissues with insulin-independent glucose uptake (lens, retina, peripheral nerve, kidney). Glucose → sorbitol (aldose reductase, NADPH consumer) → fructose (sorbitol dehydrogenase, NAD+ consumer). Hyperglycemia drives flux through this pathway, producing osmotic stress (sorbitol accumulation), NADPH depletion (oxidative stress; impaired glutathione regeneration), and AGE precursor generation (fructose is more reactive than glucose). Proposed mechanism for diabetic neuropathy, retinopathy, cataracts. Aldose reductase inhibitors (epalrestat, ranirestat) developed for diabetic neuropathy with mixed clinical outcomes — epalrestat approved in Japan + China but not in Western markets.