Biochemistry Chapter on Hemoglobin and Myoglobin

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Questions and Answers

What is the primary consequence of HbS aggregation in sickle cell disease?

Prevention of erythrocyte deformability (correct)

Stabilization of glutamic acid by hydrogen bonds

Increased oxygen affinity of hemoglobin

Formation of excess beta chains in erythrocytes

How does the structure of HbS differ from HbA at the molecular level?

HbS replaces glutamic acid with valine in the sixth position (correct)

HbS has a higher concentration of alpha-globin chains

HbS forms dimers instead of polymers

HbS contains an additional iron atom in its structure

What type of anemia may result from an imbalanced production of globin chains?

Iron deficiency anemia

Hereditary hemolytic anemia (correct)

Sickle cell anemia

Folic acid deficiency anemia

What constitutional feature causes sickle-shaped cells to become trapped in capillaries?

Disruption of the erythrocyte membrane Signup and view all the answers

Which condition is characterized by a deficiency of alpha-globin production?

Alpha-thalassemia Signup and view all the answers

What structural classification does hemoglobin (Hb) belong to?

Tetramer composed of alpha and beta subunits Signup and view all the answers

What is the key structural change in deoxyHb that initiates the aggregation of HbS?

Shift of position 6 to the cell surface Signup and view all the answers

Which of the following statements about myoglobin (Mb) is correct?

Mb is a monomer with a single polypeptide chain. Signup and view all the answers

What is the primary structural feature of globins?

Consist of alpha helices and a hydrophobic pocket Signup and view all the answers

What is unique about the haem group in globins?

It is embedded within a hydrophobic pocket of the protein. Signup and view all the answers

In adult humans, what is the predominant form of hemoglobin present?

HbA (adult hemoglobin) Signup and view all the answers

How many heme groups can each globin molecule bind to oxygen?

One heme group per globin Signup and view all the answers

What is the effect of the mutation that causes sickle cell anaemia?

It changes a polar amino acid to a non-polar one. Signup and view all the answers

How does HbF differ from HbA in its interaction with BPG?

HbF has reduced BPG binding which increases its affinity for oxygen. Signup and view all the answers

What characteristic defines sickle cell trait?

Carriage of one copy of the mutant gene without symptoms. Signup and view all the answers

What is the result of the hydrophobic patches on β-globin caused by the sickle cell mutation?

They contribute to the aggregation of hemoglobin molecules. Signup and view all the answers

What role does the mutation of β-globin play in sickle cell disease severity?

It is the primary cause of the disease severity. Signup and view all the answers

Which of the following statements about HbS is true?

HbS results from an inherited mutation of β-globin. Signup and view all the answers

What is the role of the Fe2+ ion in the haem group?

It can form bonds with ligands, facilitating oxygen transport. Signup and view all the answers

What is the significance of hydrophobic residues in globin?

They prevent the oxidation of Fe2+ to Fe3+. Signup and view all the answers

Which form of haemoglobin is unable to bind oxygen?

Met-haemaglobin Signup and view all the answers

What characteristic shape does the oxygen saturation curve of haemoglobin exhibit?

Sigmoid Signup and view all the answers

What is allostery in the context of haemoglobin?

A process where binding of oxygen increases the affinity of other binding sites. Signup and view all the answers

What ion form is incapable of participating in oxygen binding?

Fe3+ (ferric) Signup and view all the answers

Which amino acid residue is specifically mentioned as binding to the Fe2+ ion in the haem group?

Histidine Signup and view all the answers

What effect does the occupancy of haemoglobin have on its affinity for oxygen?

It increases as more oxygen binds. Signup and view all the answers

How does a decrease in pH affect the ability of hemoglobin to bind oxygen?

It decreases hemoglobin's affinity for oxygen. Signup and view all the answers

What physiological condition causes an increase in H+ concentration in peripheral tissues?

Increased production of carbon dioxide. Signup and view all the answers

At a physiological pH, what is the dissociation status of carbonic acid?

It dissociates into bicarbonate and protons. Signup and view all the answers

In the lungs, what effect does high pO2 have on hemoglobin?

It increases the formation of oxyhemoglobin. Signup and view all the answers

What is the pKa value of deoxyhemoglobin at physiological pH?

7.8 Signup and view all the answers

What process is facilitated by carbonic anhydrase in the context of oxygen transport?

Synthesis of carbonic acid from carbon dioxide. Signup and view all the answers

Which factor directly contributes to hemoglobin releasing most of its oxygen in peripheral tissues?

Increased levels of carbon dioxide. Signup and view all the answers

How does oxyhemoglobin affect the acidity in erythrocytes?

It increases the acidity by dissociating into bicarbonate. Signup and view all the answers

Study Notes

Structure of Hemoglobin (Hb) and Myoglobin (Mb)

Hemoglobin (Hb) is a tetramer consisting of 2 identical alpha globin and 2 identical beta globin subunits, forming a dimer of dimers (α1β1)(α2β2).
Myoglobin (Mb) is a monomer and has a similar structure to Hb, with both containing approximately 150 amino acids arranged in alpha helices.
Each globin has a heme group located in a hydrophobic pocket, with the hydrophilic side facing outward to bind oxygen (O2).
Each heme group has the ability to bind one oxygen molecule.

Haem Group

The heme group contains a ferrous iron (Fe2+) ion that can bond with six ligands: four from nitrogen atoms of the heme, one from a histidine in the globin, and one for reversible O2 attachment.
Hemoglobin exists in two forms: Oxyhemoglobin (oxyHb) and Deoxyhemoglobin (deoxyHb).
Hydrophobic residues within globins prevent oxidation of Fe2+ to Fe3+, which cannot bind oxygen (methemoglobin, metHb).

Cooperative Oxygen Binding

Hemoglobin exhibits cooperative binding, with oxygen saturation curves showing a sigmoid shape; affinity for O2 increases with occupancy.
Allostery occurs when binding of O2 to one globin changes the shape of the others, affecting their binding dynamics.
Reduced pH lowers Hb's affinity for oxygen, with significant saturation differences: at pH 7.4, 50% saturation occurs at pO2 ~27 mm Hg, while at pH 7.0, it occurs at ~40 mm Hg.

Impact of [H+] on Oxygen Binding

Tissues utilize oxygen and produce carbon dioxide, which is converted to carbonic acid (H2CO3) by carbonic anhydrase.
Increased [H+] from dissociation of carbonic acid drives hemoglobin to release more oxygen.
Hb's pKa is higher in deoxygenated form at pH 7.8, facilitating proton binding and enhancing oxygen release.

Oxygen Saturation in Lungs

In the lungs, high pO2 leads to increased oxyHb formation; oxyHb is more acidic (pKa 6.8) and dissociates at physiological pH.
Increased [H+] within erythrocytes shifts bicarbonate equilibrium towards carbonic acid, facilitating CO2 transport.

Sickle Cell Anaemia

Sickle cell anaemia is a recessively inherited condition characterized by the formation of sickle-shaped red blood cells due to a mutation in β-globin (glu6 to val).
This mutation creates sticky patches on β-globin, leading to polymerization of hemoglobin, termed HbS.
Individuals may exhibit sickle cell trait (one mutant gene) or sickle cell disease (two mutant genes).

HbS Aggregation and Sickle Cell Formation

Deoxygenated HbS undergoes conformational change, causing transitory shifts and aggregation into polymers, disrupting erythrocyte membranes.
Sickle-shaped cells have decreased deformability and can get trapped in capillaries, leading to cell lysis and blockages.

Insufficient dietary iron intake can lead to anemia.
Hereditary hemolytic anemia caused by an imbalance in globin chain production includes:
- α-thalassaemia: reduced α-globin production, leading to excess beta chains and formation of HbH (β4) in adults and Hb Barts (γ4) in fetuses.
- β-thalassaemia: reduced β-globin production, which also includes hereditary persistence of fetal hemoglobin (HPFH).

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Description

This quiz explores the structure of hemoglobin (Hb) and myoglobin (Mb), focusing on their subunit compositions and functionalities. It covers the details of hemoglobin's tetrameric nature and the significance of its alpha and beta globin subunits. Test your knowledge on these essential biomolecules studied in biochemistry and molecular biology.