Chapter 3, Exam 2 Content

2,3-biphosphoglycerate (2,3-BPG)

found in RBC in similar concentration to Hb

• significantly lowers the oxygen affinity of Hb

• allosteric effector

2,3-BPG lowers oxygen affinity by…

binds in a pocket of tetramer found only in the T state

• During the T-to-R transition the pocket collapses and 2,3-BPG is released 

• Hemoglobin remains in the lower affinity T state until higher oxygen concentrations are reached

• In the presence of 2,3-BPG more oxygen-binding sites within the hemoglobin tetramer must be occupied in order to induce the T-to-R transition 

Allosteric effector

A small molecule that affects the properties of a protein or enzyme by binding to a site distinct from the active site

Bohr effect

The observation that H+ and CO2 promote the release of oxygen from oxyhemoglobin (also allosteric effectors)

protons as allosteric effectors

Hb O2 affinity decreases as proton concentration increases

• increase in H+ allows for multiple ionic interactions that stabilize the T state which leads to O2 release

carbon dioxide as allosteric effector

Hb O2 affinity decreases as CO2 concentration increases

• CO2 reacts with terminal amino groups to form carbamate ion

• carbamate participates in ionic interactions that stabilize T state —> increases O2 releases

Sickle-cell anemia

A blood disease associated with distortion of red blood cells into a crescent shape when deprived of oxygen caused by a single amino acid substitution in one hemoglobin chain

• single amino acid change in beta chain causes disease —> E6V

• new valine residue lies on the surface of the T-state molecule (Figure 3.34). This new hydrophobic patch interacts with another hydrophobic patch formed by Phe 85 and Leu 88 of the β chain of a neighboring molecule to initiate the aggregation process