Lecture 8 & 10 Hemoglobin

Question 1

Erythropoeisis

Answer 1

Formation of RBCs
Starts at pluripotent stem cell ends at 2^11
Only other time you have proliferation like this is with Cancer

Question 2

Erythrocytes

Answer 2

No nucleus, no DNA and no regeneration
120 day lifespan
Use glycolysis
B12 and Folic acid are main builders
Biconcave shape

Question 3

Free iron

Answer 3

Toxic
Most common type of childhood poison
Transitional metal 2+ or 3+

Question 4

RBC ruptures

Answer 4

Releases Hgb into the cell

3 serum proteins to clean it up -haptoglobin, transferrin

Question 5

Hemoglobin is a

Answer 5

Tetramer

Question 6

Hemoglobin is a tetramer

Answer 6

Has quaternary structure that provides stability and regulation
Each has a heme - a porphyrin ring with iron
Behaves like a dimer of dimers - interact with each other

Question 7

Globin chain made of

Answer 7

Eight alpha-helices

a, b, c, d, e, f, g, h

Question 8

2 Alpha like chains

Answer 8

1. Zeta

2. Alpha

Question 9

4 Beta like chains

Answer 9

1. Epsilon - embryonic
2. Gamma - fetal
3. Delta - tiny bit of this
4. Beta - adult, 1 week after birth

Question 10

Embryonic Hgb

Answer 10

Epsilon

Question 11

Fetal Hgb

Answer 11

Gamma

Question 12

Small amount of this type Hgb

Answer 12

Delta

Question 13

Adult Beta like chain

Answer 13

Beta

Question 14

Leghemoglobin

Answer 14

1st branch of Hgb tree

Question 15

Myoglobin

Answer 15

2nd branch of Hgb tree

Chromosome 22

Question 16

Hemoglobin Alpha

Answer 16

3rd branch of Hgb tree

Chromosome 16

Question 17

Hemoglobin Beta

Answer 17

Last branch of Hgb tree
Chromosome 11
Not sure evolutionary purpose

Question 18

Typical patient has this type of Hgb

Answer 18

A2B2

Question 19

Hgb exists in

Answer 19

2 conformations
One is oxygenated
Alpha helix is dominant

Question 20

Porphyrin ring and Fe 2+

Answer 20

Heme group
4 per
Iron binds to oxygen

Question 21

2 parts of Heme

Answer 21

Porphyrin Ring

• heterocyclic tetrapyrrole
• planar and hydrophobic
• bound to globin chain

One Fe 2+ per chain

• 4 per tetrameric molecule
• Oxygen binding

Question 22

Porphyrin Ring

Answer 22

Heterocyclic tetrapyrrole
Planar and hydrophobic
Bound to globin chain

Question 23

One Fe 2+ per

Answer 23

Chain

• 4 per tetrameric molecule
• oxygen binding

Question 24

Fe 3+ is

Answer 24

Met hemoglobin

Question 25

Histidines

Answer 25

Proximal and Distal | -around the heme iron

Question 26

Function of Hgb

Answer 26

Transport of O2

Question 27

Mechanism of O2 Binding

Answer 27

- Fe 2+ : O2 binding site - Cooperativity - intrasubunit communication - Reversible binding - Allosteric control

Question 28

O2 binding site

Answer 28

Fe 2+

Question 29

Allosteric control

Answer 29

*occurs throughout biochemistry Where something other than substrates can regulate how it binds -3 molecules that bind to Hgb and change the conformation

Question 30

Sigmoidal curve shows the

Answer 30

Cooperativity | -steep part shows the cooperativity

Question 31

Cooperativity

Answer 31

``` Multi-subunit protein Subunits exist in 1 of 2 conformations Conformational change in one subunit induces a conformational change in another -many stable contact points -some contact points change ```

Question 32

Conformational change in one subunit....

Answer 32

Induces a conformational change in another

Question 33

Structure of Myoglobin

Answer 33

Monomer - can't have cooperativity because it is a monomer One Globin chain -different gene - still has exact same fold, so 3D structure is identical One Heme- Fe2+

Question 34

Allosteric control

Answer 34

Regulation of O2 affinity Effectors -bind to distinct sites (NOT active site) -induce conformational change -inhibit O2 binding - so deoxygenated conformation

Question 35

Negative Allosteric Effectors - 3 things that cause this

Answer 35

1. Bind to distinct sites (not active site) 2. Induce conformational change 3. Inhibit O2 binding - so deoxy conformation

Question 36

Negative Allosteric Effectors

Answer 36

Protons (low pH) CO2 2,3-bisphosphoglycerate

Question 37

Negative Allosteric Effector Proton

Answer 37

Low pH AKA H+ *slight acidification during burn of E (fuel)

Question 38

Negative Allosteric Effector CO2

Answer 38

Ex. fire, byproduct is CO2, same as burning sugar or fat in mitochondria, CO2 is released

Question 39

Negative Allosteric Effector BPG

Answer 39

``` 2,3-bisphosphoglycerate In clinical called DPG An intermediate in glycolysis One step rxn, enzyme for that is found in RBC they make it Make more in high altitudes ```

Question 40

R and T Forms of Hemoglobin

Answer 40

R - Deoxyhemoglobin | T - Ocyhemoglobin

Question 41

O2 curve for fetus

Answer 41

To the L Fetal has higher affinity for O2 because fetus is not breathing, mother is BPG in fetus is decreased so O2 is increased

Question 42

Fetal Hgb and BPG

Answer 42

BPG is decreased in fetus, so it increases oxygen, so it shifts it to the L AA sequence is different

Question 43

Hb F

Answer 43

Fetal Hgb 2 alphas, 2 gammas Behave differently that Hgb A (maternal) AA sequence doesn't allow to bind to BPG so they have higher affinity for O2