Biosynthesis of Purine Nucleotides: De-novo Pathway and MCQs GPAT, NEET, NET, UPSC and Pharmacist Exam

Purine and pyrimidine are dietary non-essential components. Dietary nucleic acid and nucleotides do not provide essential components for the synthesis of endogenous nucleic acids.

In humans, the synthesis of nucleic acid is done by de-novo routes, that its through amphibolic intermediates.

Biosynthesis of purine nucleotides means synthesis of AMP and GMP.

De-novo pathway for the synthesis of purine nucleotides:

In this method, synthesis of new product this done using amphibolic intermediates, that is the one which are already used in other reactions

In this process, the purine ring is formed from different structures like:

• Glycine provides C₄, C₅ and N₇ of purine
• Aspartate provides N₁
• Glutamine provides N₃ and N₉
• Tetrahydrofolate (THF) derivates provide C₂ and C₈
• CO2 provides C₆

Using all these precursors, a ring structure is formed

Steps involved in the pathway-

1. The pathway begins with ribose-5-phosphate which is converted into phospho-ribosyl-pyro-phosphate (PRPP) through PRPP synthetase enzyme
2. Amide group of glutamine is added to PRPP and forms 5-phosphoribosylamine through glutamine PRPP aminotransferase enzyme. This is the 1^st rate limiting step in formation of IMP.
3. Now glycine is added to 5- phospho-ribosyl-amine to form glycinamide ribonucleotide(GAR)
4. 1 carbon unit I transferred to amino group of GAR to form formyl glycinamide ribonucleotide (FGAR) through GAR formyl transferase
5. Another animation of glutamine and ATP forms formyl glycinamidine ribonucleotide (FGAM)
6. In this reaction, ring structured is formed and loss of water to form amino-imidazole ribonucleotide (AIR)
7. Addition of CO2 to AIR forms carboxy-aminoimidazole ribonucleotide (CAIR). This reaction neither requires biotin nor ATP
8. Aspartate is condensed with CAIR to form N-succinyl-5-aminoimidazole-4-carboxamide ribonucleotide (SAICAR).
9. Succinyl group of SAICAR is liberated as fumarate and forms aminoimidazole carboxamide ribonucleotide (AICAR)
10. Addition of N¹⁰ formyltetrahydrofolate to AICAR forms formyl aminoimidazole carboxamide ribonucleotide (FAICAR)
11. Ring structure of FAICAR forms the 1^st purine nucleotide, inosine mono-phosphate(IMP)
12. Both AMP and GMP are formed from IMP. Using nitrogen of aspartate, AMP is formed and using nitrogen of glutamine, GMP is formed.
13. Addition of aspartate to IMP forms adenylo-succinate through adenylosuccinate synthetase and GTP.
14. Removal of fumarate from adenylosuccinase forms AMP.
15. For GMP, IMP is first oxidized to xanthosine mono-phosphate (XMP) by NAD⁺.
16. XMP accepts an amino group from glutamine and forms GMP.

Regulation of De-novo pathway

Control in the synthesis of purine nucleotide is done by two factors:

• Concentration of PRPP– It depends on two factors:
  1. Availability of ribose-5-phosphate
  2. Activity of PRPP synthetase
• Feedback regulation at different sites
  1. PRPP synthetase- it is inhibited during high concentration of AMP and GMP
  2. Glutamine PRPP amidotransferase- inhibited in case of high concentration of AMP, GMP and IMP
  3. Adenylosuccinate synthase- inhibited by AMP
  4. IMP dehydrogenase- inhibited by GMP

Multiple Choice Questions MCQs

1. Purine and pyrimidine are nutritionally classified as which type of components?
A. Essential

B. Non-essential

C. Semi-essential

D. None of the above

2. Synthesis of purine nucleotide can be done through how many process?
A. 2

B. 3

C. 4

D. 1

3. What are amphibolic intermediates?
A. Intermediates never used
B. These are one used only in certain physiologic condition
C. Intermediates already used
D. All of the above

4. C4 of purine nucleotide is derived from which precursor?
A. Glycine

B. Aspartate

C. Glutamine

D. None of the above

5. Which of the enzyme catalyzes the rate limiting step for the formation of IMP?
A. PRPP synthetase

B. GAR formyl transferase

C. IMP dehydrogenase

D. None of the above

6. Aspartate provides which of the following component of purine component?
A. N1

B. N7

C. N3

D. N9

7. Which of the following are included in purine nucleotide?
A. CMP, GMP

B. AMP, UMP

C. AMP, GMP

D. CMP, AMP

8. Match the following-
9. Addition of CO2 produces which compound in purine synthesis pathway?
A. AIR

B. CAIR

C. GAR

D. FGAR

10. Which of the following compound is a common intermediate in both De-novo pathway and salvage pathway?
A. PRPP

B. GAR

C. FGAM

D. none of the above

11. Succinyl group of SAICAR is liberated as which compound?
A. lactate

B. pyruvate

C. fumarate

D. both A and c

12. Which of the following statement is NOT true?
13. Which of the following enzymes regulate the de-novo synthesis of purine nucleotide?
A. PRPP synthetase

B. glutamine PRPP amido-transferase

C. IMP dehydrogenase

D. All of the above

14. Regulation of the de-novo synthesis of purine nucleotide depends on the concentration of which compound?
A. Ribulose-5-phosphate

B. PRPP

C. IMP

D. AIR

15. Ring structure of which of the compound forms IMP?
A. AICAR

B. FAICAR

C. both

D. none

ANSWERS:

1. Non-essential
2. 2
3. Intermediates already used
4. Glycine
5. None of the above
6. N1
7. AMP, GMP
8.
9. CAIR
10. PRPP
11. Fumarate
12
13. All of the above
14. PRPP
15. FAICAR