Structure of Hemoglobin

Oxygen hemoglobin dissociation curve, is the curve relating percentage saturation of the oxygen carrying power of hemoglobin to the Po2. It has a characteristic sigmoid shape due to the T-R interconversion. In deoxyhemoglobin, globin units are tightly bound in a tense (T) configuration which reduces the affinity of the molecule for oxygen.

A i.e. Sigmoid curve of oxygen dissociation & B i.e. Positive co-operativity

Unlike Myoglobin, hemoglobin shows:

–  Tetrameric structure

–  Can bind four 0₂ moleculeQ

–  Sigmoid saturation kineticsQ

–  Co-operativity or co-operative binding kinetics: property that permits it to bind a maximal quantity of 0₂ at respiratory organs & to deliver a maximal quantity of 0₂ at

peripheral tissue. Here binding of Hb with 02 facilitates binding of other 0₂ molecules thus positive co-operativity.

A i.e. Binding of one oxygen molecule increases the affinity of binding other 0, molecule

Ans. is ‘c’ i.e., Gower

Ans. A: HbA

In the embryo-Gower 1 (C₂ r₂) Gower 2 (a2E2)

In the fetus: hemoglobin F (a2y2)

In the adults:

Hemoglobin A (GA) – The most common with a normal amount over 95%

Hemoglobin A 2 (a₂6,) – Chain synthesis begins late in the third trimester and in adults, it has a normal range of 1.5-3.5%

Hemoglobin A1c is increased in the patients with poorly controlled diabetes mellitus

Ans. is `b’ i.e., Cooperative binding in Hb

• Cooperative binding is responsible for sigmoid shape of the oxygen-hemoglobin dissociation curve.
  
• As myoglobin is monomeric (consists of one polypeptide chain only), it can bind only one molecule of oxygen and for the same reason myoglobin cannot show the phenomenon of cooperative binding. Hence, the oxygen‑myoglobin dissociation curve is hyperbola as compared to sigmoid shape of Hb-O₂ curve.

Hemoglobin – O₂  binding

• Each molecule of hemoglobin can combine with upto four molecules of oxygen. Combination with the first molecule alters the conformation of the hemoglobin molecule in such a way as to facilitate combination with the next oxygen molecule. In light of this, if we look at the curve, as the PO₂ starts rising from 0 mm Hg upwards, initially all hemoglobin molecules in blood starts combining with their first oxygen molecule. This is the most difficult molecule to combine with. Hence saturation rises only slowly with initial rise in PO₂. As PO₂ rises further, hemoglobin molecules combine with their second, third and fourth molecules, which are progressively easier to combine with. Hence saturation rises steeply between PO₂ of 15 mm Hg and 40 mm Hg. When PO₂ rises still further, oxygen finds most of the hemoglobin molecules carrying four molecules of oxygen each. Since no molecules of hemoglobin can carry more than four molecules of oxygen, there is not much scope for more O₂ combining with hemoglobin. Hence the curve becomes almost flat again beyond the PO₂ of 60 mm Hg.
• Thus, the primary reason for the sigmoid shape of the oxygen-hemoglobin dissociation curve is that out of the four molecules of oxygen that can combine with a hemoglobin molecules, the first combines with the greatest difficulty and binding of an oxygen molecules increases affinity to next O₂ molecule. This phenomenon is termed as cooperative binding or cooperativity, i.e., a molecule of O₂ binds to a hemoglobin tetramer more readily if other O₂ molecules are already bound.

Myoglobin O₂  binding

• Myoglobin is present in higher concentration in red (slow) muscle fibers. Myoglobin has greater affinity for oxygen than hemoglobin and its P₅₀ is only 5 mm Hg (as compared to PO₂ of hemoglobin which is about 26 mm Hg). Therefore, myoglobin-oxygen dissociation curve is shifted far to the left than Hb-O₂ dissociation curve. It has shape of hyperbola as compared to sigmoid shape of Hb-O₂ curve because it binds 1 molecule of O₂ per mole (in comparison to Hb which binds 4 molecules of O₂ per mole). The role of myoglobin is to bind O₂ at very low PO₂ and release them at even lower PO₂, for example in exercising muscles where PO₂ close to zero.

Ans. is ‘a’ i.e., 16 and 11

Ans. is ‘a’ i.e., 1

Hemoglobin is the most important red cell constituent.

The hemoglobin molecule is an assembly of four globular protein.

Each subunit is composed of a protein (polypeptide) part, i.e., globin and a nonprotein part i.e., heme, i.e., Each hemoglobin molecule contains four heme units and two pairs of similar protein, globin.

The heme part of globular protein is same in all types of hemoglobin.

The protein part vary in different hemoglobin : ‑

1.  Adult hemoglobin (Hemoglobin A) consist of two identical a-chains and two identical n-chains.
2. Fetal hemoglobin (H bF) consists of two identical a-chains and two identical y chains.
3. Minor hemoglobin (HbA₂) consist of two identical a-chains and two identical 8 chains.

Each hemoglobin molecule consists of globin (4 polypeptide chains) and 4 heme molecules.

Ans. is ‘b’ i.e., Low affinity for 2,3 DPG

Make it very clear in mind that higher affinity of fetal hemoglobin for oxygen is due to low affinity of HbF for 2,3­DPG (not due to decreased 2, 3-DPG concentration). HbF does not combines to 2, 3-DPG as avidly as adult hemoglobin.

Ans. is ‘d’ i.e., 4

• Hemoglobin is a conjugated protein which has a tetrameric structure.
• It is an assembly of four globular proteins.
• Each subunit is composed of a protein part, i.e. globin and a nonprotein prosthetic group, i.e. heme.
• Each hemoglobin molecule is made up of 4 heme molecules and 4 polypeptide chains (2 pairs of similar polypeptide chains).

Hemoglobin=Globin (containing 4 polypeptide chains)+ 4 heme molecules

Ans. a. pH

Increase in pH (Alkalosis) can cause a shift of the oxygen-hemoglobin dissociation curve lo the left.
Exercise: Oxygen dissociation Curve shifts to the right in exercising muscles.
Alkalosis (increased pH), hypothermia (decreased temperature), hypocarbia (decreased p C02, and decreased 2,3, DPG
cause left shift of O2, dissociation curve)

Ans. is ‘a’ i.e., Each hemoglobin molecule is made of 4 polypeptides of each subunit