5: Hemoglobin
The Bohr effect states that:
- Hemoglobin's oxygen binding affinity is inversely related both to acidity and to the concentration of carbon dioxide.
Structure of Myoglobin
- It is a globular protein which consists of a single polypeptide chain that is folded into eight stretches of helix. - It can carry only one oxygen based on its structures. - It also consist mainly of alpha helices where the interior of the myoglobin molecule is composed mainly of non polar amino acids. - While the polar amino acids are located on the surface of the molecule, where they can form hydrogen bonds with each other and with the water.
Quarternary structure of hemoglobin
- It is composed of two identical dimers (alpha beta) 1 and (alpha beta 2) dimer where the polypeptide chains such as alpha and beta subunits are held together by hydrophobic interactions. - And the alpha-beta dimer 1 and alpha-beta dimer 2 are held together by ionic and hydrogen bonds hence, able to move with respect to each other.
How is the heme group bound to myoglobin?
- One, the proximal histidine, binds directly to the iron of heme. - Second, the distal histidine, doesn't interact with the heme group, but helps stabilize the binding of oxygen to the ferrous iron.
R form of hemoglobin
- Relaxed form. - It is the oxygenated form of hemoglobin. - It means that there is a high oxygen-affinity form of hemoglobin. - In "R form", it is easier for the oxygen to find and attach to the heme.
T form of hemoglobin
- Taut or Tense form. - It is the deoxygenated form of hemoglobin. - It means that there is a low oxygen-affinity form of hemoglobin. - In "T form", it is difficult for the oxygen to find and attach to the heme.
What are the allosteric ("other site") effectors that can affect the ability of hemoglobin in order to bind to the oxygen?
1. by pO2 (through heme-heme interactions) 2. the pH of the environment 3. the partial pressure of carbon dioxide (pCO2). 4. the availability of 2, 3-bisphosphoglycerate.
How much is the p50 when the oxygen dissociation curve shifts towards the left?
17 mmHg
How does BPG regulate hemoglobin?
2,3 Bisphosphoglycerate (BPG) binds only to deoxyhemoglobin. Therefore, BPG lowers the oxygen affinity of hemoglobin by shifting the T ⇌ R equilibrium to the left.
The affinity of hemoglobin for CO is ________ times greater than for oxygen.
220
How much is the p50 when the oxygen dissociation curve is normal?
26 mmHg
How much is the p50 when the oxygen dissociation curve shifts towards the right?
36 mmHg
Hemeproteins
A group of specialized proteins that contain heme as a tightly bound prosthetic group.
prosthetic group
A non-protein, but organic, molecule (such as vitamin) that is covalently bonded to a protein to permit its function.
Hemoglobin
An iron-containing protein in red blood cells that reversibly binds oxygen.
Myoglobin
An oxygen-storing, pigmented protein in heart and skeletal muscle cells.
What has the highest affinity to hemoglobin?
Carbon monoxide as it binds tightly but reversibly to the hemoglobin iron.
Hemoglobin A
Composed of 4 polypeptide chains, 2 alpha chains and 2 beta chains which is held together by non-covalent interactions (as it is a quaternary structure). - each subunit has stretches of alpha- helical structure, and a heme-binding pockets similar to myoglobin.
Structure of heme
Heme is a complex of protoporphyrin IX and ferrous iron (Fe 2+). The iron is held in the center of heme molecules by bonds to the 4 nitrogens of the porphyrin ring and and interacts with two histidine residues.
Which is the major hemoglobin in adults?
Hemoglobin A
In oxygen dissociation curve, what shape does the myoglobin has?
Hyperbolic shape
What does it mean when the oxygen dissociation curve shifts to the left?
Increased affinity for oxygen.
Why is BPG important at high altitudes?
Increasing the concentration of 2,3-BPG in our blood shifts the oxygen binding curve to the right side. This means that hemoglobin will have a lower affinity for oxygen and will be able to release more oxygen to the tissues and cells of our body.
How many molecule of oxygen can hemoglobin bind?
It can bind to four oxygen molecules - one at each of its four heme groups.
Function of myoglobin
It functions both as a reservoir for oxygen and as an oxygen carrier that increases the transport of the oxygen within the muscle cell.
Co-operative binding of oxygen in hemoglobin
It means that the binding of an oxygen molecule at one heme group increases the oxygen affinity of the remaining heme groups in the same hemoglobin molecule. This effect is called as heme-heme interaction. - Although it is difficult for the first oxygen molecule to bind to hemoglobin, the subsequent binding of oxygen occurs with high affinity almost 300 times greater than the first O2 molecule.
Bohr effect
It reflects that the deoxy form of hemoglobin has a greater affinity for protons than does of oxyhemoglobin.
How does the allosteric effectors have an affect on the hemoglobin?
It's because their interaction at one site of the hemoglobin molecule affects the binding of oxygen to heme groups at other locations on the molecule.
Does BPG make hemoglobin more or less cooperative?
Less cooperative as being able to deliver more O2 to the peripheral tissues.
Which gas molecule is a potent vasodilator?
Nitric Oxide (NO) gas as it can be taken or released from RBCs, hence increasing the diameter of the blood vessels.
Does 2,3-BPG increase affinity for oxygen?
No, 2,3-DPG decreases oxygen affinity and vice versa.
How many molecule of oxygen can myoglobin bind?
One oxygen molecule because it contains only one heme group.
Under what conditions oxyhemoglobin dissociation curve shifts to the right?
Oxygen dissociation to the right is shifted by increase in 2,3-BPGS, increased temperature and increased pH (alkalosis).
In oxygen dissociation curve, what shape does the hemoglobin has?
S-shaped or Sigmoidal shape.
What does the oxygen dissociation curve illustrates?
The graph illustrates that the myoglobin has a higher oxygen affinity at all pO2 values than of hemoglobin.
What happens when the carbon mono-oxide binds to one of the four heme sites in hemoglobin?
The hemoglobin shifts to the relaxed state shifting the oxygen dissociation curve to the left, changing its normal sigmoidal shape to the hyperbola shape. Hence, it is unable to release oxygen to the tissues.
Oxygen dissociation curve
The oxygen dissociation curve is a graph with oxygen partial pressure along the horizontal axis (X) and oxygen saturation on the vertical axis (Y), which shows an S-shaped relationship.
What does the oxygen dissociation curve illustrates at the partial pressure of oxygen?
The partial pressure of oxygen needed to achieve half-saturation of the binding sites (P50) is approximately 1 mmHg for myoglobin and 26 mmHg for hemoglobin.
Main function of hemoglobin
To transport oxygen from the lungs to the capillaries of the tissues.
When does oxygen-binding curve shifts to the left side?
When there is a decrease in 2,3-BPGS, decreased temperature, increased pH (alkalosis), and binding or increase of Carbon monoxide (CO).
Does 2/3 BPG increase anemia/hypoxia?
Yes, as increase in 2/3 BPG allows the oxygen to be released into the tissues.
Allosterism
a change in the activity and conformation of an enzyme/protein resulting from the binding of a compound at a site on the enzyme/protein other than the active binding site
What are the most abundant hemeproteins in humans?
hemoglobin and myoglobin
In Bohr effect; a decrease in carbon dioxide or increase in blood pH will result in
hemoglobin picking up more oxygen. (High affinity of o2)
In Bohr effect; a decrease in blood pH or an increase in blood CO2 concentration will result in
hemoglobin proteins releasing loads of oxygen.
In higher altitudes or COPD/emphysema, there is low levels of oxygen but ______ levels of 2,3-BPG. This means that it is able to release more oxygen to the tissue and cells of the body.
high
Holoprotein
protein with prosthetic group.
Apoprotein
protein without its prosthetic group (heme).
