Biology 3601 Fall 2013

Hemoglobin Function

In the lungs, the concentration of oxygen is high. As a result of positive cooperativity, when the oxygen concentration is high, the affinity of hemoglobin for oxygen is high. As a result, hemoglobin binds tightly to oxygen.

In the tissues, the concentration of oxygen is low. As a result of positive cooperativity, when the oxygen concentration is low, the affinity of hemoglobin for oxygen is low. As a result, hemoglobin binds weakly to oxygen, which is released into the tissues.

Carbon Dioxide Transport

Hemoglobin also ‘carries’ CO and H+

Reaction catalyzed by the enzyme carbonic anhydrase.

HHb+ + O2  HbO2 + H+

His146 makes a major contribution to the Bohr effect. When protonated, it forms an ion pair that stabilizes Hb in the T state.

high CO2 = high [H+] (low pH)

Bohr effect: a decrease in the amount of O2 associated with Hb in response to low blood pH from an increased [CO2] in the blood.

Effect of pH on O2 Binding to Hemoglobin

Hb has higher kd at lower pHs

Carbon Dioxide Transport

also contributes to Bohr effect

2

Heterotropic Allosteric Regulation

HbBGP + O2  HbO2 + BPG

Found naturally in blood, binds in the histidine lined central cavity of hemoglobin

and blocks T to R transition

2,3-BPG and Tense Hemoglobin

2,3-bisphosphoglycerate

In the absence of 2,3-BPG in our blood, hemoglobin would be too effective at transitioning to the R-state; hemoglobin would always be bound to oxygen.

2,3- BPG

Fetal Hemoglobin

a2b2

a2g2

2-BPG does not bind as well to fetal hemoglobin as adult hemoglobin

Sickle Cell Anemia

http://www.fairview.org/fv/groups/public/documents/images/176949.jpg

Hemoglobin S

Missense Mutations of Hemoglobin

Thalassemia

b-variant: Heterozygous loss of b-chains produces a mild phenotype. Homozygous loss of b-chains is more severe. Some individuals survive for a short time by extending production of g (fetal) hemoglobin.

a-variant: There are two copies of the alpha gene-a1 and a2 (four alpha genes per individual). When only one alpha gene is present, anemia results. b4 and g4 tetramers can assemble to compensate but they are fixed in the R-state and are not cooperative. When all four copies of the alpha chain are missing, the result is hydrops fetalis (stillbirth).

Crocodile Ice Fish

http://www.coolweirdo.com/wp-content/uploads/2014/01/antarctic-young-icefish-de.jpg

The only known vertebrates to lack red blood cells and hemoglobin, survive due to relatively low metabolic rates and the ability of sufficient oxygen to dissolve in their blood