Why does sorbitol accumulate in lens fiber cells of patients with chronic hyperglycemia, even though sorbitol dehydrogenase is present?
- A Sorbitol is rapidly converted to fructose, which precipitates as crystals in the lens
- B Insulin deficiency completely blocks the polyol pathway at the aldose reductase step
- C Sorbitol dehydrogenase has low affinity for sorbitol, and sorbitol cannot cross cell membranes readily, so it becomes trapped osmotically ✓
- D Aldose reductase is competitively inhibited by accumulated fructose in diabetics
Correct answer: C. Sorbitol dehydrogenase has low affinity for sorbitol, and sorbitol cannot cross cell membranes readily, so it becomes trapped osmotically
Explanation
Aldose reductase reduces glucose to sorbitol using NADPH, and sorbitol dehydrogenase normally oxidizes sorbitol to fructose. In hyperglycemia, glucose influx overwhelms this second step because sorbitol dehydrogenase has a high Km for sorbitol. Since sorbitol crosses membranes poorly, it accumulates intracellularly, drawing water in by osmosis and producing lens swelling and cataracts. Insulin-independent tissues such as lens, nerve, and kidney are most affected, explaining option B's error.
Reference: Lippincott Illustrated Reviews: Biochemistry, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.