Cpwk1 Genetics 11-4 - Hemoglobin

Front 1

How many RBCs are produced per second?
How long do RBCs last?

Back 1

2.4 mill
last 120 days

Front 2

What occurs if there is a problem in the yolk sac of the fetus at 1-2 months?
At what point does the tissue switch for RBC production and how this relates to globin switching?

Back 2

RBC production may be hurt

- at 9 months 95% of RBCs made in bone marrow

- When Hemoglobin is made in different tissue it has different structure and altered function...
In fetal Hb is HbF and made in liver
In newborns 50-85% is HbF
At Year One 95% is HbA

Front 3

Describe the basic structure of hemoglobin

Back 3

4-subunit protein (tetramer)
• Each subunit has one Heme with (ferrous iron Fe2+) and Four protoporphyrin IX rings
– 2 α-2 β globin chains have 2 forms T and R and (97% HbA a2B2):

Front 4

Explain The importance of the T and R forms of Hb

Back 4

Biggest reason Hb has sigmoid O2 dissociation curve, because it switches between two states depending on PO2 and other factors
T (taut) for has low affinity for O2
R (relaxed) form has high affinity for O2 (300x)
- Important that increased Cl, H, CO2, 2,3-BPG, and temperature favor T form, which lead to O2 unloading (at tissues- Bohr effect)

Front 5

Name the globin proteins for the
a. a-like chains
b. B-like chains
Which chromosome does each group associate with?

Back 5

a. (zeta), a (alpha)- chromosome 11
b. (epsilon), (gamma), (delta), (beta)- Chromosome 16

Front 6

Describe what is happening with Hb in Sickle cell anemia...(Name specific amino acid # and substitution) What symptoms does this cause?
What is research in HbF trying to do?

Back 6

- HbS at amino acid 6 in B-globin shows substitution of valine for glutamic acid which causes HbS to polimerize
- The sickle shaped red blood cells impeded circulation (pain, organ damage, strokes, increased infections)
- Trying to induce HbF to stop HbS expression and replace it with gamma globin

Front 7

Describe the conformational changes of hemoglobin after O2 binds

Back 7

Upon oxygenation, the iron ion moves into the plane of the heme and pulls down the proximal F8 histidine (which is attached to globin chain). This is important because it changes the interaction with associated globin chain and affects the function of Hb

Front 8

How many RBCs are produced per second?
How long do RBCs last?

Back 8

2.4 mill
last 120 days

Front 9

Describe the structure and components of the Heme group inside hemoglobin...

Back 9

Two components
1. Organic component ("protporyphyrin")- four pyrrole rings
to form a tetrapyrrole ring.
- Attachments include:
a. 4 methyl groups
b. 2 vinyl groups
c. 2 propionate side chains
2. Central iron atom- in center of protoporphyrin-
Attachments:
The 4 pyrrole nitrogen atoms

Front 10

Describe the labeling of the amino acids by what helical segment (out of 8 possible ones) they are in.
What are the proximal and distal histidines?

Back 10

8 segments labeled A - H, named according to segment and # amino acid (ex. F8 histidine is 8th amino acid residue on F segment)

Proximal- F8 bound to heme group
Distal- E7 O2 bind to iron between the two histidines

Front 11

compare and contrast myoglobin and hemoglobin in the following ways...
a. roles
b. structure of myoglobin

Back 11

a. Myoglobin stores O2 has super high affinity for O2 and Hemoglobin transports O2
b. monomer encoded by different genes compared to tetramer Hemoglobin,

Front 12

What part of the O2 dissociation curve shows steepest part of oxygen binding curve?

Back 12

20-40 torr which is when it goes from ~30-75% saturation
- proves that Hb is effective in providing oxygen to exercising tissues

Front 13

A Hb molecule has 4 heme groups which allows for 4 O2 molecules to bind... what happens when one O2 binds...
- what structurally is going on here?

Back 13

Begins the confirmational change and Hb grows higher affinity for O2

- O2 to Fe pulls proximal F8 histidine which pulls globin a-helix and changes interaction with other globin chains "positive cooperativity"

Front 14

Explain what the pH levels have on the binding affinity of Hb and how this relates to the idea known as the Bohr Effect.

Back 14

lower pH = lower Hb binding affinity for O2
Tissues have lower pH and therefore O2 is made to unload from Hb
- This phenomenon is known as the Bohr effect, where essentially the pH of a certain area will determine whether O2 will be unloaded or loaded

Front 15

Why is it important for HbF (fetal Hemoglobin) to have higher affinity for O2 than HbA (adult hemoglobin)?
How does this occur?

Back 15

It needs higher affinity because it is already getting less oxygenated blood than mother's tissues (end of mother's circulated blood) so it must me very effecient
- it does not bind well to 2,3-BPG so unloading does not occur as often and HbF keeps high affinity for O2

Front 16

What is the phenomena known as carboxyhemoglobin?

Back 16

- Heme combines with CO due to 210x bonding strength of O2
- impairs transport of 02 to tissues

Front 17

What gene is monitered to see "report card" for diabetic control?

Back 17

HbA1c- post translational modificaiton of glucose with n-terminus of B-globin chain non- reversible (usually 3% in normal people
- % related blood glucose concentration in 120 day lifespan of RBCs
- Report card because 2-3x higher in diabetics, but if measured every 120 days you can compare to see if diabetes is better or worse controlled.