After two weeks of trekking at 4500 m, a climber's red cell 2,3-BPG concentration rises significantly compared to sea level values. The effect of this adaptation on hemoglobin function is:

• A Increased oxygen affinity with a left-shifted dissociation curve, improving pulmonary oxygen loading
• B Conversion of hemoglobin to the R-state at all oxygen tensions
• C Decreased oxygen affinity with a right-shifted dissociation curve, enhancing oxygen unloading in tissues ✓
• D No change in affinity, because 2,3-BPG binds equally to oxyhemoglobin and deoxyhemoglobin

Explanation

2,3-BPG binds only the central cavity of deoxyhemoglobin, formed by positively charged residues of the beta chains, and stabilizes the T-state. At altitude, hypoxia raises red cell 2,3-BPG, lowering hemoglobin oxygen affinity and raising P50. This right shift favors oxygen release in tissues, partially offsetting the low inspired PO2. BPG binds deoxyhemoglobin far more avidly than oxyhemoglobin, so option D is wrong.

Reference: Lehninger Principles of Biochemistry, 7th ed.

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