Haem Heme and Haemoglobin synthesis

Question 1

which the rate determining step in Heme synthesis

Answer 1

1). 2 Glycine + 2 Succinyl CoA–> Delta Aminoluvenic acid (ALA)
Enzyme: ALA Synthase
2Glycine+ 2Succinyl CoA—> 4Pyrrole
B6 is the coenzyme for this reaction

Question 2

What is the process of Heme Synthesis

Answer 2

1). 2 Glycine + 2 Succinyl CoA–> Delta Aminoluvenic acid (ALA)
Enzyme: ALA Synthase
2). Aminoluvenic acid–>Porphobilinogen
Enzyme: ALA Dehydratase
3). Porphobilinogen–>Hydromethylbilane
Enzyme: Porphobilinogen Deaminase
4). Hydromethylbilane–>Uroporphorynogen III
5). Uroporphorynogen III–>Corproporphorynogen III
Enzyme: Uroporphyrynogen III Decarboxylase
6). Corproporphorynogen III–> Protoporphyrin IX
7). Protoporphyrin IX + Fe2+–> Heme
Enzyme: Ferrochelatase

Question 3

What processes take place on the Mitochondria and cytosol?

Answer 3

Mitochondria:
1). Glycine +Succinyl CoA –> ALA
2). Protoporphyrin IX+ FE2+–>Heme

Cytosol
ALA–>Porphobilinogen
Porphobilinogen–>Hydroxymethylbilane
Hydroxymethylbilane–>Urobilinogen III
Urobilinogen III–> Coproporphyrinogen III

Question 4

Haemoglobin Synthesis

Answer 4

A.A–>ALPHA & Beta chains
Alpha and Beta chains–>Alpha2Beta2 Chains
Alpha2Beta2 Chains+ Heme–> Haemoglobin

Question 5

What is the Overall process of Hb Synthesis?

Answer 5

2 Glycine + 2 Succinyl CoA–> 4 pyrrole
4 Pyrrole–>Protoporphoryn IX
Protoporphyrin IX + Fe2+–> 4 Heme
4 Heme+ polypeptide–> Haemoglobin chain
2 Alpha + 2 Beta Chains–> Haemoglobin A

Question 6

What are some defects from Heme Synthesis?

Answer 6

1). Sideroblastic Anaemia
-Congenital Sideroblast. anaemia is caused by ALAS2 gene gene defect in the ALA enzyme.

2). Lead poisoning
XS lead inhibits the action ALA Dehydratase and Ferrochelatase.
stops rxn of ALA to porphobilinogen
and Protoporphyrin IX to Heme

3). Porphyrias
-Rare
Can be inherited in autosomal pattern OR
Acquired through Xs Alcoholism, smoking, sun exposure, liver disease

Question 7

What are different types of Hb

Answer 7

1).Hb A
-adult Hb after 3-6 months
-95% of total Hb
2 Alpha and beta chains

2).Hb A2
-2-3% of total Hb
-2 alpha and 2 delta chains

3).Hb F
-0.5- 0.8 % of total Hb
- aka Foetal Hb
-Has a higher affinity for O2 for efficient O2 transport from mother to child.

4).Hb S
-Sickle cell anaemia
-mutation in gene of beta chain subs of valine for glutamic acid

5).Hb C
-Haemolytic Anaemia
-Mutation in Beta chain sub of Lysine for Glutamic acid on 6 position

6). Hb D
-Prevelant in Pujab
-North-West Indian with a 2 % frequency

7). Hb E
-Structural variant of A
-Substitution of Lysine for glutamic acid on 26th position of beta chain

Question 8

what are the classifications of Globin Chain disorders?

Answer 8

1). Quantitative- substitution of one A.A
2). Qualitative-Thalassemia whole chain defect

Question 9

What are the Types of Thalassaemia?

Answer 9

Firstly it is inherited

1). Alpha Thal Major-Complete absence of alpha chain
2).Alpha+Thal Minor- Absence of one chain- moderate anaemia
3).Alpha+ Thal carrier- no anaemia
4). B Thal major-severe anaemia
5). B+ Thal minor-mild anaemia