A newborn male is noted to have hemolytic anemia, jaundice, and splenomegaly. Red cell enzyme assay shows markedly reduced activity of phosphofructokinase-1 (PFK-1). Which best explains why PFK-1 deficiency causes hemolysis?

• A Accumulation of fructose-6-phosphate inhibits NADPH generation
• B ATP depletion impairs Na+/K+-ATPase pump function in erythrocytes ✓
• C Excess glycolytic intermediates directly oxidize hemoglobin
• D Reduced 2,3-BPG leads to impaired oxygen delivery

Explanation

PFK-1 catalyzes the committed, rate-limiting step of glycolysis converting fructose-6-phosphate to fructose-1,6-bisphosphate. Mature erythrocytes depend entirely on anaerobic glycolysis for ATP production because they lack mitochondria. Deficiency of PFK-1 severely restricts ATP synthesis, impairing the Na+/K+-ATPase membrane pump, causing osmotic swelling and premature hemolysis.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.