A 25-year-old woman from West Africa presents with mild chronic hemolytic anemia and splenomegaly. Hemoglobin electrophoresis at alkaline pH shows a band migrating between HbA and HbS positions. Hemoglobin C (HbC, beta6 Glu→Lys) is diagnosed. Why do HbC erythrocytes form crystals (unlike HbS which forms fibers) under dehydration?
- A The Lys substitution creates positive charges that form electrostatic bonds with adjacent beta chains in an organized lattice ✓
- B Glutamic acid at position 6 is required for deoxyHb polymerization, and its absence prevents fiber formation but allows crystal lattice
- C HbC has increased oxygen affinity, keeping hemoglobin in the oxy conformation that favors crystallization
- D HbC crystals result from oxidation of the Lys residue to form cross-links
Explanation
In HbC, glutamate at beta-6 is replaced by lysine — changing from a negatively charged to a positively charged residue at the surface. Unlike HbS (Glu→Val, hydrophobic), HbC in the deoxy state forms intracellular crystals rather than long polymers; the positive Lys residues create inter-molecular electrostatic interactions with nearby acidic residues on adjacent tetramers, forming a tightly packed orthorhombic crystal lattice. HbC erythrocytes are rigid and have reduced deformability, causing mild hemolysis. HbSC disease (compound heterozygote) causes sickling crises intermediate in severity between HbSS and HbAS.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
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