Chapter 7: Hemoglobin

Question 1

p₅₀ for myoglobin

Answer 1

2 torr

Question 2

p₅₀ for hemoglobin

Answer 2

26 torr

Question 3

Hemoglobin structure

Answer 3

Quaternary protein with four separate polypeptide chains working together

Two ⍺ and two β chains that are like myoglobin and can bind oxygen via heme

Question 4

Heme structure

Answer 4

Functional unit of both myoglobin and hemoglobin

Protoporphyrin ring binds iron

Iron must be ferrous (Fe²⁺) to bind oxygen

Histidine helps support the iron as well

When unbound to oxygen the Fe²⁺ is forced 0.4 Å out of the plane of the ring

Question 5

Binding sites to Fe²⁺

Answer 5

Fe²⁺ has six binding sites

4 are to nitrogens of the pyrrole rings

The 5th coordination site is the to the proximal histidine

The 6th is to the oxygen molecule

Question 6

Hemoglobin states

Answer 6

The quaternary structure of deoxyhemoglobin is the T state (tense) and is constrained by subunit-subunit interactions

The quaternary structure of the fully oxygenated oxyhemoglobin is the R state (relaxed) which is free of strain and capable of binding oxygen with higher affinity

Question 7

2,3-Bisphosphoglycerate

Answer 7

2,3-Bisphosphoglycerate (2,3-BPG) stabilizes the T state of deoxyhemoglobin and thus facilitates the release of oxygen

Without 2,3-BPG hemoglobin would be an extremely inefficient oxygen transporter

Question 8

fHgb

Answer 8

Fetal hemoglobin doesn’t have β chains but has ɣ chains instead

Reduces capability of 2,3-BPG to bind to fHGB which increases the binding of oxygen to fetal hemoglobin

Question 9

Bohr Effect

Answer 9

CO₂ and H⁺ produced by actively respiring tissues enhance oxygen release by hemoglobin and are thus allosteric effectors

The lower pH stabilizes the T state which favors the release of oxygen

Question 10

Sickle-Cell Anemia

Answer 10

Caused by a mutation in the β chain of hemoglobin that replaces a glutamate residure with a valine in position 6

• G6V

Predominantly affects the T state

Question 11

Thalassemia

Answer 11

Caused by the absence or underproduction of one of the hemoglobin chains

α-thalassemia- not enough of the α chain of hemoglobin is produced so the tetramers that form contain only the β chain

• These tetramers bind oxygen with high affinity and no cooperativity; release of O₂ in the tissues is poor

β-thalassemia- not enough of the β chain of hemoglobin is produced so the tetramers that form contain only the β chain

• α chains form insoluble aggregates that precipitate inside immature red blood cells

Alpha is rarer than beta and more complex inheritance pattern emerges

Beta has homozygous recessive inheritance