Synthesis of Hemoglobin and MCQs GPAT, NEET UPSC, Pharmacist, CSIR NET and Nursing Exam

Synthesis of heme –

It takes place in almost all the cells but largely in bone marrow and liver. This happens because in liver and bone marrow, the requirements for the incorporation of heme into hemoglobin and cytochromes are high.

Biosynthesis of heme is divided in 3 stages:-

Biosynthesis of delta-aminolevulinate (ALA) from glycine and succinyl-CoA.
Formation of porphobillinogen (PBG) from two molecules of delta-aminolevulinate (ALA)
Conversion of PBG to the cyclic tetra-pyrrol porphyrin ring and heme.

The first and the last step of the biosynthesis reaction is catalyzed in mitochondria while the intermediate steps are catalyzed in cytosol.

Reactions of biosynthesis of heme

The first step in the biosynthesis is the condensation of glycine and succinyl-CoA to form ALA. Other than ALA synthase enzyme, PLP (pyridoxal phosphate) is also necessary. This is the rate controlling step.
Two molecules of ALA condense to form 2 molecules of water and 1 PBG molecule; catalyzed by PBG synthase, where this is zinc requiring enzyme.
4 PBG molecule condense to form ,linear tetra-pyrrol. Further, linear tetra-pyrrol forms a cyclic structure known as uroporphyrinogen-3. Here the basic ring structure is formed
Uroporphyrinogen-3 is further converted to coproporphyrinogen-3 by decarboxylation of acetate side chains to methyl groups.
Corpoporphyrinogen-3 is then converted into protoporphyrinogen-9 by corpoporphyrinogen oxidase. This enzyme is able to act only on type-3 corpoporphyrinogen; that’s why type-1 protoporphyrin do not occur in nature.
The oxidation of protoporphyrinogen-9 to protoporphyrin is catalyzed by protoporphyrinogen oxidase.
Finally, incorporation of ferrous ion in protoporphyrin in a reaction forms heme by heme synthase enzyme.

This picture is taken only for educational purpose from th.bing.com

Several factors regulate the synthesis of heme which are discussed below-

ALA synthase enzyme which catalyzes the rate controlling step is feedback inhibited by excess product (heme)
Excess level of heme inhibits the synthesis of delta-aminolevulinic acid synthase and decreased level of heme stimulates the synthesis of delta-aminolevulinic acid synthase
Two iron atom activates heme synthesis

Several substances like steroid hormones, ethanol, barbiturates, metabolites etc stimulates the synthesis of ALA synthase enzyme.

Multiple Choice Questions (MCQs)

1. Biosynthesis of heme mainly takes place in which organ?
A. Liver

B. Muscle

C. Bone marrow

D. Both A and C

2. What is the location for initial and final steps of the biosynthesis of heme?
A. Cytosol

B. Nucleus

C. Mitochondria

D. Ribosomes

3. What is the location for intermediate steps of the biosynthesis of heme?
A. Cytosol

B. Nucleus

C. Mitochondria

D. Ribosomes

4. biosynthesis of heme is divided in how many stages?
A. 2

B. 3

C. 4

D. 5

5. Which of the following enzyme catalyzes the rate determining step of biosynthesis of heme?
A. PBG synthase

B. ALA synthase

C. Heme synthase

D. both A and C

6. Which compound begins the process for the biosynthesis of heme?
A. Vinyl groups

B. Acetyl-CoA

C. Glycine

D. All of the above

7. How many molecules of ALA is required for its condensation to form PBG?
A. 2

B. 3

C. 4

D. 5

8. Match the following enzymes and its substrates-

A. ALA synthase 1. Coproporphyrinogen-3

B. PBG synthase 2. protoporphyrin

C. Heme synthase 3. ALA

D. Coproporphyrinogen oxidase 4. Succinyl-CoA

9. Which of the following enzyme requires zinc?

A. PBG synthase

B. ALA synthase

C. Heme synthase

D. both A and B

10. Why do type-1 protoporphyrin do not generally occur in nature?

A. coproporphyrinogen oxidase only act on type-1 coproporphyrinogen

B. coproporphyrinogen oxidase only act on type-2 coproporphyrinogen

C. coproporphyrinogen oxidase only act on type-3 coproporphyrinogen

D. coproporphyrinogen oxidase only act on type-4 coproporphyrinogen

11. Which of the following inhibits ALA synthase enzyme?

A. Excess heme

B. Steroid hormones

C. Ethanol

D. All of the above

12. Which of the following statement is NOT true?

A. 2 molecules of ALA condenses to form only 1 water molecule

B. In 3rd step, basic ring structure is formed

C. Iron atom activates heme synthesis

D. Initial steps occur in mitochondria

13. Which of the following compound is also known as hydroxyl-methylbilane?

A. Succinyl-CoA

b. Uroporphyrinogen-3

C. Linear tetra-pyrrol

D. None of the above

14. decarboxylation of which side chain compound to methyl groups converts uroporphyrinogen-3 to corpoporphyrinogen-3?

A. Vinyl group

B. Acetate

C. Proprionate

D. All of the above

15. Which ion activates the biosynthesis of heme?

A. Calcium

B. Potassium

C. Sodium

D. None of the above

ANSWERS-
1. Both A and C
2. Mitochondria
3. Cytosol
4. 3
5. ALA synthase
6. Glycine
7. 2
8. a – 4 b – 3 c – 2 d – 1
9. PBG synthase
10. Coproporphyrinogen oxidase only act on type-3 coproporphyrinogen
11. All of the above
12. 2 molecules of ALA condenses to form only 1 water molecule
13. Linear tetra-pyrrol
14. Acetate
15. None of the above

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REFERENCE:- 1. Pankaja Naik- Biochemistry; 4^th edition; page no:- 313-315