Haemoglobin Structure, Functions and Degradation Flashcards
Briefly explain the structure of hemoglobin.
🩸 Hemoglobin is composed of four polypeptide chains - two alpha (α) chains and two non-alpha chains.
🩸 Each of these chains is attached to a heme group, which contains an iron atom at its center [incorporated in its ferrous form]. This iron atom is crucial as it binds to oxygen molecules.
🩸 The four chains together form a quarternary structure, allowing hemoglobin to carry up to four oxygen molecules at a time.
What are some types of hemoglobin?
(a) HbA
🩸 2 alpha (α) and 2 beta (β) chains
🩸 This is the most common type in adults, making up about 95-98% of hemoglobin in the body.
(b) HbA2
🩸 2 alpha (α) and 2 delta (δ) chains
🩸 Constitutes about 2-3% of adult hemoglobin. Its exact function is similar to HbA but is less abundant.
(c) HbF
🩸 2 alpha (α) and 2 gamma (γ) chains
🩸 Predominant in fetuses and newborns, facilitating efficient oxygen transfer from the mother’s blood to the fetus. It is gradually replaced by HbA after birth.
(d) HbS
🩸 2 alpha (α) and 2 beta (β) chains with a mutation in the beta chain
🩸 Found in individuals with sickle cell disease. It can cause red blood cells to become rigid and sickle-shaped, leading to various complications.
Explain the mutation involved in HbS.
◾ The mutation occurs in the HBB gene, which is located on chromosome 11.
◾ It is a single base-pair point mutation where the codon GAG (which codes for glutamic acid) is changed to GTG (which codes for valine). Glutamic acid is thus substituted for valine.
◾ This substitution occurs at the 6th position of the beta-globin chain.
Haemoglobin is ____(a)____% saturated when it leaves the lungs. Under resting conditions it is about ____(b)____% saturated when it returns.
(a) 97
(b) 75
Briefly discuss the helical structure of haemoglobin and the position of the heme group.
🩸 Hemoglobin is a tetramer, meaning it is composed of four polypeptide chains.
🩸 Each polypeptide chain is arranged in a helical structure.
🩸 There are eight helical segments in each chain, designated as A to H.
🩸 The heme group contains an iron (Fe) atom that is essential for oxygen binding.
🩸 The iron atom in the heme group is covalently bound to a histidine residue at position F on the H segment of the polypeptide chain.
[Diagram]
The haem part of haemoglobin is synthesized in the ____(a)____, whereas the globin part is synthesized in the ____(b)____.
(a) mitochondrion [and partly in the cytoplasm]
(b) ribosome
Briefly describe the structure of haem.
🩸 Haem is composed of a large ring-like molecule known as a porphyrin. This ring is made up of four smaller rings called pyrroles, which are connected by methine bridges. The entire structure is known as a tetrapyrrole.
🩸 At the centre of this porphyrin ring is an iron ion (Fe²⁺). This iron ion is crucial because it can bind to oxygen molecules. The iron is held in place by the nitrogen atoms of the pyrrole rings.
🩸 The porphyrin ring has various side chains attached to it, which can vary slightly depending on the type of haem.
The ferrous iron (Fe²⁺) in heme has six coordination sites, which means it can form six bonds with surrounding atoms or molecules. State how each of these coordination sites are occupied.
🩸 4 are bound to pyrrolic nitrogens in the ring
🩸 1 is used for globin binding through a histidine residue
🩸 1 is used for oxygen binding in the lungs
[Diagram]
Outline the process of heme synthesis.
(1) Condensation of glycine and succinyl-CoA. This occurs in the mitochondria and results in the formation of δ-aminolevulinic acid (ALA). This reaction is catalyzed by the enzyme ALA synthase.
(2) ALA then moves to the cytoplasm, where ALA dehydratase converts two molecules of ALA into porphobilinogen (PBG).
(3) Four molecules of PBG are converted into hydroxymethylbilane by the enzyme porphobilinogen deaminase. This intermediate then cyclizes to form uroporphyrinogen III.
(4) Uroporphyrinogen III undergoes decarboxylation by uroporphyrinogen decarboxylase to form coproporphyrinogen III.
(5) Coproporphyrinogen III is transported back into the mitochondria, where it is converted into protoporphyrinogen IX by coproporphyrinogen oxidase.
(6) Protoporphyrinogen IX is then oxidized to protoporphyrin IX by protoporphyrinogen oxidase.
(7) Finally, ferrochelatase inserts an iron ion into protoporphyrin IX to form heme.
Discuss the regulation of heme synthesis.
Heme synthesis is tightly regulated, primarily at the level of ALA synthase, which is inhibited by high levels of heme and glucose to prevent overproduction.
Heme formation
____________ is a coenzyme of ALA synthase.
Pyridoxal 5’-phosphate
List the various types of globin chains.
Alpha (α) chains, Beta (β) chains, Gamma (γ) chains, Delta (δ) chains, Epsilon (ε), chains, Zeta (ζ) chains
Embryonic haemoglobin comprises ________ and ________ globin chains.
ζ, ε
The synthesis of globin follows the same process as any other protein: Transcription, Translation and Assembly. Outline the genes involved.
Globin genes are organized into two clusters:
(1) Alpha-Globin Gene Cluster (located on chromosome 16):
HBA1 and HBA2: Encode the alpha chains.
HBZ: Encodes the zeta chain.
(2) Beta-Globin Gene Cluster (located on chromosome 11):
HBB: Encodes the beta chain.
HBG1 and HBG2: Encode the gamma chains.
HBD: Encodes the delta chain.
HBE1: Encodes the epsilon chain.
Haemoglobin formation
What are molecular chaperones?
Molecular chaperones are proteins that assist in the proper folding of other proteins, preventing misfolding and aggregation.
