U01.01.100 Sorbitol

Sorbitol serves as an alternative pathway for glucose metabolism, particularly in tissues where glucose metabolism may lead to complications under hyperglycemic conditions. Understanding the sorbitol pathway and its implications is crucial for USMLE Step 1.

Key Steps in Sorbitol Pathway

Conversion of Glucose to Sorbitol
- Enzyme: Aldose reductase
- Reaction: Glucose + NADPH → Sorbitol + NADP⁺
Conversion of Sorbitol to Fructose
- Enzyme: Sorbitol dehydrogenase
- Reaction: Sorbitol + NAD⁺ → Fructose + NADH

Tissue-Specific Enzyme Distribution

Tissue	Aldose Reductase	Sorbitol Dehydrogenase
Liver, Ovaries, Seminal Vesicles	Present	Present
Lens	Present	Absent
Retina, Kidneys, Schwann Cells	Present	Absent

Mnemonic for Enzyme Activity:

Liver, Ovaries, and Seminal vesicles: They “LOSe” sorbitol (have both enzymes).
Lens, Retina, Kidneys, Schwann Cells: LuRKS (primarily aldose reductase, lacking sorbitol dehydrogenase).

Clinical Significance of Sorbitol Accumulation

Osmotic Damage
- Occurs in tissues lacking sorbitol dehydrogenase.
- Sorbitol buildup increases osmotic pressure, leading to cellular swelling.
Complications in Diabetes
- Cataracts: Sorbitol accumulation in the lens causes lens opacity.
- Retinopathy: Damage to retinal cells due to osmotic stress.
- Peripheral Neuropathy: Schwann cells are vulnerable to sorbitol-induced damage.
Galactitol Formation
- High galactose levels (e.g., in galactosemia) are converted to galactitol by aldose reductase, leading to similar osmotic issues.

Points to Remember for USMLE Step 1

Aldose reductase converts glucose to sorbitol and galactose to galactitol.
Tissues with insufficient sorbitol dehydrogenase are prone to osmotic damage.
Mnemonic for tissue enzyme distribution:
- LOSe: Liver, Ovaries, Seminal vesicles have both enzymes.
- LuRKS: Lens, Retina, Kidneys, Schwann cells rely primarily on aldose reductase.
Diabetes complications like cataracts and neuropathy are linked to sorbitol buildup.

USMLE Step 1 Exam Tip

Questions on the sorbitol pathway often focus on its role in diabetic complications or its enzyme distribution. Use the mnemonics and enzyme activity map to quickly eliminate incorrect options.

References

Harper’s Illustrated Biochemistry
Lippincott’s Illustrated Reviews: Biochemistry
First Aid for the USMLE Step 1

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