Biochemistry · Carbohydrate Metabolism (Glycolysis, Gluconeogenesis, Glycogen, HMP Shunt)

A newborn presents on day 2 with vomiting and jaundice after breastfeeding. Urine reducing substances are positive but glucose oxidase test is negative. Diagnosis is galactosemia (GALT deficiency). The toxic metabolite responsible for cataracts in this condition is:

  • A Galactose-1-phosphate accumulating in lens cells
  • B Galactitol formed by aldose reductase in the polyol pathway
  • C UDP-galactose accumulating in lens epithelium
  • D Galactonate formed by galactose oxidase
Correct answer: B. Galactitol formed by aldose reductase in the polyol pathway

Explanation

In GALT-deficient galactosemia, galactose cannot be converted to glucose-1-phosphate (G1P). Excess galactose enters the polyol pathway via aldose reductase, converting galactose to galactitol (a sugar alcohol). Galactitol accumulates in the lens (which lacks the enzyme to further metabolize it), creating an osmotic gradient that draws water in, causing osmotic swelling and cataract formation. Galactose-1-phosphate accumulation (option A) is responsible for hepatocellular, neurological, and gonadal toxicity in galactosemia, but not cataracts. This mechanism is identical to how sorbitol causes cataracts in diabetic lens.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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