Small-molecule effectors and the Bohr/BPG effects on hemoglobin Which option best summarizes how small molecules commonly modulate hemoglobin oxygen affinity in vivo?

Introduction / Context:
Hemoglobin’s oxygen affinity is tuned by several small molecules, notably protons (H+), carbon dioxide, and 2,3-bisphosphoglycerate. These effectors are central to the Bohr effect and to the adaptation of oxygen delivery to metabolic demand.

Given Data / Assumptions:

• Tissues generate CO2 and H+, and red cells contain BPG.
• Higher H+ and BPG favor the T state (lower affinity).
• Lungs have lower H+ and release CO2, favoring higher affinity.

Concept / Approach:
Increasing H+ concentration (lower pH) protonates specific residues and stabilizes salt bridges that favor the T state, shifting the O2 dissociation curve to the right (higher P50). BPG binds the T state cavity and further lowers affinity. Together, these factors enhance unloading of O2 in tissues.

Step-by-Step Solution:
Identify effectors: H+, CO2 (via carbamates and acid formation), and BPG.Mechanistic outcome: stabilization of T state, decreased affinity, improved tissue delivery.Select the option that captures increased [H+] with decreased affinity.

Verification / Alternative check:
Experimental O2 binding curves show rightward shifts with added acid or BPG; removal of BPG shifts curves left, increasing affinity.

Why Other Options Are Wrong:
Statements that isolate only one effect miss the coupled nature; increasing affinity at higher H+ contradicts the Bohr effect; decreasing [H+] typically increases affinity, not decreases it.

Common Pitfalls:
Assuming all small molecules increase affinity; in vivo, the dominant systemic effectors in tissues generally decrease affinity to promote unloading.

Final Answer:
Increasing [H+] and decreasing Hb affinity for O2.