Biochemical Myoglobin and Haemoglobin/Hemoglobin Structure, Properties, and Binding
Below are some notes on myoglobin and hemoglobin that can be used for an understanding or refresher that is helpful and useful for the sciences; specifically biology, chemistry, and biochemistry.
- Has a metal ion Fe (II)
- Protoporphyrin IX
- Can be bound by O2 or CO
- Has an affinity for CO that is 25,000x greater than its affinity for O2
- CO binds at an angle due to the steric interactions caused by Histidine E7
- CO's binding advantage over O2 drops by two orders of magnitude due to His E7
- This angled binding is so that CO produced during metabolism would not take up the O2 binding sites.
- The angled binding is also so that the heme is able to let O2 go when the body needs it.
- When the heme is without the protein, the iron in the heme group can be oxidized to Fe (III). In this form it will not bind oxygen.
- Is the same for myoglobin and hemoglobin.
- Is a globular protein
- Has 3o structure
- Is made up of one polypeptide chain of 153 amino acid residues and a prosthetic heme group
- Has a compact structure with interior atoms close together
- Has 8 alpha-helical parts
- Has 0 beta-pleated sheet regions
- Has stabilized alpha-helical regions due to H-bonding in the in the polypeptide backbone
- Is used for oxygen storage in the muscles
- Has to bind oxygen at low pressures
- Binds oxygen reversibly
- Has a hyperbolic binding curve
- Has s higher percentage of saturation than hemoglobin at any oxygen pressure
- Oxygen-binding ability is not affected by H+ or CO2
To bind O2 need : [heme] + [protein]
- Missing one or the other will not allow O2 binding
A Note on CO2
*CO2 is dangerous in large amounts because it can bind to the heme group in myoglobin and hemoglobin, and because of the final step in the electron transport chain where O2 is the finale e- acceptor.
- Has 4 five-membered rings
- Four rings linked by connecting methine groups
- Fe (II) has 6 sites at which it can bond
- Fe (II) binds to five nitrogens; one of these nitrogens is on the imidazole side-chain of histidine residue F8
- Fe (II) binds to one oxygen
Myoglobin Simplified: Binding
Myoglobin Simplified: Binding 2
- In hemoglobin alpha-chain and beta-chain refers to differences in polypeptide chains not alpha-helix or beta-pleated sheet conformations.
Positive Coopertativity=once one oxygen molecule binds to hemoglobin it becomes easier for the subsequent oxygen to bind.
Cooperative Binding=The first oxygen binding makes it easier for the second oxygen to bind. The second oxygen makes it easier for the third oxygen to bind. The third oxygen makes it easier for the fourth oxygen to bind to hemoglobin.
- Has 4 subunits: 2 alpha-chains, 2 beta-chains
- Alpha-chain has 141 residues
- Beta-chain has 146 residues
- Each subunit has one heme group
- Can bind 4 oxygen molecules
- Binds oxygen reversibly
- Exhibits positive cooperativity and cooperative binding
- Has a sigmoidal binding curve
- Is used for oxygen transport
- Binds oxygen in the alveoli of the lungs to transport to tissues
- Gives up oxygen easily in the capillaries
- Is an allosteric protein; has different conformations in its bound and unbound forms
- Is oxygenated in the bound form with 2 beta-chains that are close together
- Is deoxygenated in the unbound form with 2 beta-chains that are not as close together
- Binds to both H+ and CO2
Fetal hemoglobin has a higher affinity for oxygen than maternal hemoglobin
Metabolizing tissue releases H+ and requires O2. In metabolizing conditions, hemoglobin has a lower affinity for oxygen and releases oxygen when there is need of it.
Hemoglobin's acid-base properties and interactions both affect and are affected by its oxygen-binding properties.
*Oxgenated hemoglobin=stronger acid/lower pKa
*Deoxygenated hemoglobin has higher H+ affinity than the oxygenated form of hemoglobin.
Conformational Changes of Hemoglobin
The binding of H+ and CO2 to hemoglobin changes its structure and affect its affinity for oxygen.
- H+ affects hemoglobin's oxygen-binding ability
- Increase in H+=lower in pH=protonates amino acids at the N-terminals of alpha-chains and His146 of the beta-chains
- Protonated His146 is attracted to/stabilized by a salt bridge to Asp94; favors the deoxygenated form of hemoglobin.
- The deoxygenated form of hemoglobin has 4o structure.
In the lungs:
In actively metabolizing tissue:
Higher pH than actively metabolizing tissue
Lower pH because of H+ production
Hemoglobin binds O2
Hemoglobin releases O2
Hemoglobin releases H+
Hemoglobin binds H+
Normal blood pH= 7.4
High levels of H+ + CO2 (respiring tissue) =hemoglobin releases O2
High levels of O2 (lungs)=hemoglobin binds O2
Effects of CO2
CO2 is produced in metabolism and forms carbonic acid.
Most of the dissolved CO2 in the blood will be in the form of bicarbonate ion which releases H+.
Larger amounts of H+ as a result of CO2 production favors the 4o structure of deoxygenated hemoglobin, lowering hemoglobin's affinity for oxygen.
The Bohr Effect reflects a process that fine-tunes pH, CO2, and O2 levels within the body.
"Stripped" hemoglobin=hemoglobin that is isolated from blood and that has had BPG removed; 50% of this hemoglobin is bound to oxygen at 1 torr.
BPG makes it so that enough oxygen is released in the capillaries.
Effects of BPG
Hemoglobin binds to BPG.
Binding of BPG to hemoglobin is electrostatic
- Negative charges on BPG interact with the positive charges on the hemoglobin protein
With BPG the partial pressure for binding 50% of the hemoglobin to oxygen is 26 torr.
Without BPG, hemoglobin's oxygen-binding capacity would be much higher ( 50% of hemoglobin would be bound at 1 torr) and not much oxygen would be let go in the capillaries.
Other Hubs in My "Notes On..." Series
The information used for this hub was taken from the following sources:
"Biochemistry" by Mary K. Campbell and Shawn O. Farrel; 7th edition.
My biochemistry lectures at school.
Knowledge and notes taken from previous courses in chemistry and biology.