Hemoglobin: Portrait of a Protein in Action

Question 1

Which 2 proteins bind oxygen at iron atoms in heme

Answer 1

Myoglobin and hemoglobin

Question 2

Myoglobin

Answer 2

Largely alpha-helical protein, binds heme

Question 3

What does heme consist of?

Answer 3

Protoporphyrin, an organic component with 4 linked pyrrole rings, and a central iron ion in the Fe2+ state

Question 4

How does myoglobin bind heme?

Answer 4

Iron ion coordinated to side chain of (proximal) histidine in myoglobin. One of O in O2 binds to open coordination site on iron. Partial electron transfer from iron to O, so ion moves into plane of porphyrin on O binding.

Question 5

What does haemoglobin consist of?

Answer 5

4 polypeptide chains, 2 alpha and 2 beta.

Question 6

How to describe the haemoglobin tetramer..

Answer 6

A pair of alpha-beta dimers

Question 7

What kind of binding is haemoglobin to oxygen and what binding curve will they have?

Answer 7

Cooperative, so binding curve is s-like (sigmoid)

Question 8

Is haemoglobin or myoglobin more efficient when binding oxygen?

Answer 8

Coop binding increases efficiency, so haemoglobin

Question 9

Quaternary structure of haemoglobin changes when bind oxygen. What are deoxyhemoglobin and oxyhemoglobin known as?

Answer 9

Deoxy = T state
Oxy = R state

Question 10

Concerted model of cooperative binding

Answer 10

Each haemoglobin is either T or R state. Equilibrium between the 2 determined by number of occupied oxygen-binding sites

Question 11

Sequential model of coop binding

Answer 11

Allows intermediate structures. Structural changes at iron sites due to oxygen binding affect T-R equilibrium

Question 12

2,3-biphosphoglycerate (2,3-BPG) concentrations in RBC’s and hemoglobin

Answer 12

Concentration approx. equal in both

Question 13

What does 2,3-BPG do?

Answer 13

Binds tightly to T state but not R state. Stabilizes T state, lowering oxygen affinity of hemoglobin

Question 14

Fetal and adult hemoglobin

Answer 14

Fetal binds oxygen more tightly, weaker 2,3-BPG binding. Allows oxygen transfer from maternal to fetal blood.

Question 15

The bohr effect

Answer 15

Increasing concentration of hydrogen ions (decreasing pH) and carbon dioxide decreases oxygen affinity of haemoglobin.

Question 16

2 mechanisms by which increase CO2 decreases oxygen affinity of hemoglobin

Answer 16

1. C02 converted to carbonic acid, decreases pH in RBC.
2. CO2 adds to amino terminal of haemoglobin to form neg charged carbamates. They stabilize deoxyhemoglobin through ionic interactions.

Question 17

What is the purpose of the Bohr effect?

Answer 17

Helps deliver oxygen to where it is most needed because hydrogen ions and CO2 are produced in rapidly metabolizing tissues.

Question 18

What is sickle cell caused by

Answer 18

Mutation in beta chain of haemoglobin which subs a valine residue for a glutamate residue.

Question 19

What happens when have the sickle cell mutation

Answer 19

Hydrophobic patch forms on surface of T-state haemoglobin, leads to formation of fibrous polymers, fibers distort RBC’s into sickle shapes.

Question 20

What causes thallassemias?

Answer 20

Reduced production of either alpha or beta chain. Resulting in haemoglobin tetramers that have only 1 type of chain.

Question 21

What happens when haemoglobin has only 1 type of chain?

Answer 21

Poor oxygen release, low solubility, leads to destruction of RBC’s.

Question 22

RBC precursors usually produce slight excess alpha chains, how is aggregation prevented?

Answer 22

alpha-haemoglobin stabilizing protein produced. Binds specifically to newly synthesized alpha chain monomers to form a soluble complex