hemoglobin up

8/14/2019 Hemoglobin Up

1/19

Hemoglobin: Portrait of a Protein

in Action


2/19

7.3 H+ions and CO2Promote the Release of Oxygen:

The Bohr Effect

Rapidly metabolizing tissuesgeneral largeamounts of H+and CO2.

To release O2where the need is greatest,

hemoglobin has evolved to respond to higherlevels of these substance. H+and CO2are

allosteric effectors of hemoglobin

The regulation of O2binding by H+

and CO2iscall Bohr effect (1904)


3/19

The oxygen affinity of Hemoglobinas pH (7.47.2): tendency to

release oxygen increases

For example: Transport The lungs (pH 7.4, 100 torr)Active muscle (pH

7.2, 20 torr):

Result: in a release of oxygen 66% (pH 7.4)

77% (pH 7.2)

At least two sets of chemical groups are important for sensing changes in

pH:

-amino groups of a chain N-term

side chains (His) of b146 and a122

pKavalues near 7


4/19


5/19

CO2stimulates oxygen release by two mechanisms

First, high concentrate of CO2leads to a drop in pH within red blood cell

(RBC)

Second, direct chemical interaction between CO2

and Hb stimulates

oxygen release

carbonic anhydrase

CO2decrease the affinity of Hbfor oxygen

H2CO3: pKa 3.5


6/19

CO2stabilizes deoxyHb by reacting with the terminal amino groupto form carbamate group (- charged)terminal amino group lie at the interface between the ab

dimerssalt bridge stabilizes the T state (favoring the release of O2)a mechanism of CO2transport (~14%)


7/19

CO2released from RBC lung (in the form of HCO3-)

exchange of HCO3-and Cl-through antiporter

Figure: transport of CO2from tissues to lungs. Most carbondioxide is transported to the lungs in the form of HCO3

- produced

in red blood cells and then release into the plasma. A lesser

amount is transport bay hemoglobin in the form of an attached

carbamate


8/19


9/19


10/19

Examination of the structure of hemoglobin S reveals that the

new valine residue lies on the surface of the T-state molecule.

Why do these aggregates not form when HbS isoxygenated?

: oxyHb in R state Phe 85, Leu88 on bchain are largelyburied inside the Hb assembly

decreased the solubility of deoxy

Hb

: Val6-Phe85, Lue88aggregationHbS fiber is formed from 14 chains

of multiple interlinked Hbs


11/19


12/19


13/19

The accumulation of free alpha-hemoglobin chain isprevented

AHSP: -hemoglobin stabilizing protein, in RBCs The ASHP binds to the chain monomers and

creates a highly soluble complex; does notprecipitate

AHSP:

- It can bind to both the oxygenated and deoxygenatedforms of the alpha chain

- Binds to the alpha chain as it is being produced-It is displaced when beta-hemoglobin is produced

-Prevents accumulation of free alpha hemoglobin


14/19

Additional globin are encoded in the human

genome

In additional to the gene for myoglobin, the two

gens for -hemoglobin, and the one for -hemoglobin, the human haploid genomecontain other globin genes.

Examination of the human genome sequencehas revealed two additional globins:neuroglobin, cytoglobin


15/19


16/19

Question

1. The amount of oxygen released by thehemoglobin molecules in the blood to thetissues

a. decreases as temperature increases

b. increases as blood pH decreases(acidityincreases)

c. decreases as pCO2increases

d. increases as pCO2decreases

B


17/19

2. Most carbon dioxide is transported as

__________ in the blood.

bicarbonate ions


18/19

3. Which of these factors increases respiratoryrate (increases release O2)?

A)increased blood pCO2

B)increased blood pH

C)increased blood pO2D)all of these

A


19/19

4. What do the three amino acids in deoxyhemoglobin form inorder to stabilize the T state quaternary structure?

salt bridges

5. How does carbon dioxide form carbamate?

by reacting with the terminal amino group

6. What is the reason thalassemia occurs?

by an imbalanced production of hemoglobin chains

hemoglobin up

Documents