De-Novo Biosynthesis of Pyrimidine Nucleotides and MCQs GPAT, NEET UPSC, Pharmacist, CSIR NET and Nursing Exam

In pyrimidine synthesis, firstly the pyrimidine ring is formed and then ribose phosphate group is attached. This ribose phosphate group is donated by PRPP (phosphoribosyl-pyrophosphate). The major pyrimidine nucleotide involve: TMP, CMP and UMP.

Precursors for the De-novo synthesis of pyrimidine nucleotides:

Glutamine provide N₃
CO2 provides C₂
Aspartic acid provides C₄, C₅, C₆ AND N₁

Steps involved:

The process begins with formation of carbamoyl phosphate from glutamine, ATP and CO2. This reaction is catalyzed by carbamoyl phosphate synthase-2 (CPS-2)
Carbamoyl phosphate is condensed with aspartic acid and forms carbamoyl aspartate. This is a committed step of biosynthesis of pyrimidine nucleotide.
After the removal of water molecules from carbamoyl aspartate, dihyroorotic acid is formed. This is ring closure of pyrimidine nucleotide.
Oxidation of dihydro-orotic acid yields orotic acid (pyrimidine derivative). This is the only reaction of the process catalyzed in mitochondria. Rest all other occurs in cytosol.
Next is Attachment of ribose phosphate group to pyrimidine ring. ribose phosphate is transferred from PRPP to orotate and forms orotidine mono-phosphate.
Decarboxylation of OMP to form uridylate (UMP)
UMP is phosphorylated to UDP; and again UDP is phosphorylated to UTP.
Addition of amino group (from glutamine) to UTP forms CTP.
Ribonucleotides are reduced to deoxy-ribonucleotides
Deoxy-UDP is dephosphorylated to deoxy-UMP which in turn forms deoxy-TMP.
Methylation of deoxy-UMP forms deoxy-TMP.

Regulation of De-novo synthesis of pyrimidine nucleotide

The first two enzymes of the process are allosteric enzymes. These are CPS-2 and aspartate transcarbamoylase.

CPS-2 is activated by PRPP and inhibited by UTP
Aspartate carbamoylase is activated by ATP and inhibited by CTP.

Multiple Choice Questions (MCQs)

1. Pyrimidine nucleotides are nutritionally classified as?
A. Essential

B. Non-essential

C. Semi-essential

D. None of the above

2. How many pathways are present for the biosynthesis of pyrimidine nucleotide?
A. 2

B. 3

C. 4

D. 1

3. C5 of pyrimidine ring is produced by?
A. Glycine

B. Glutamine

C. CO2

D. Aspartic acid

4. Where do mainly the de-novo biosynthesis of pyrimidine nucleotide occur?
A. Nucleus

B. Cytosol

C. Ribosomes

D. Endoplasmic reticulum

5. Glutamine provides which of the following components of pyrimidine nucleotide?
A. N3

B. N1

C. C4

D. C5

6. The ribose phosphate group attached to the pyrimidine ring is donated by which compound?
A.UMP

B. Orotate

C. Both

D. None of the above

7. Which compound is termed as the ring closure of pyrimidine ring?
A. Dihyro-orotic acid

B. OMP

C. Both

D. None

8. Match the following substrate and its product-
A. d-UMP 1. OMP
B. d-UDP 2. Dihydro-orotate
C. Carbamoyl aspartate 3. d- UMP
D. Orotate 4. D-TMP

9. Which of the following enzyme catalyzes the committed step of the de-novo biosynthesis of pyrimidine nucleotide?
A. Aspartate transcarbamoylase

B. Orotate phosphoribosyl transferase

C. Dihydro-orotate dehydrogenase

D. Both A and c

10. Which of the following is the starting compound for the de-novo biosynthesis of pyrimidine nucleotide?

A. Glutamine

B. Aspartic acid

C. CO2

D. Both A and C

11. Which of the following product in the process of de-novo biosynthesis of pyrimidine nucleotide is formed in mitochondria?
A. Orotic acid

B. Dihydro-orotic acid

C. Carbomoyl aspartate

D. All of the above

12. Which of the following statement is NOT true?
A. Ethylation of d-UMP forms d-TMP
B. CO2 provides C2 carbon of pyrimidine ring
C. Thymidylate synthase is a target enzyme in cancer chemotherapy
D. Decarboxylation of orotidylate yields UMP

13. Which of the following acts as precursors for the de-novo biosynthesis of pyrimidine nucleotide?
A. Glutamine

B. Aspartic acid

C. CO2

D. All of the above

14. Which of the following enzyme is inhibited by CTP?
A. CPS-2

B. Dihydro-orotase

C. Aspartate transcarbamoylase

D. Both A and B

15. Which of the following enzyme is activated by PRPP?
A. CPS-2

B. Dihydro-orotase

C. Aspartate transcarbamoylase

D. Both A and C

ANSWERS-

1. Non-essential
2. 1
3. Aspartic acid
4. Cytosol
5. N3
6. None of the above
7. Dihydro-orotic acid
8. A – 4 B – 3 C – 2 D – 1
9. Aspartate transcarbamoylase
10. Both A and C
11. Orotic acid
12. Ethylation of d-UMP forms d-TMP
13. all of the above
14. Aspartate transcarbamoylase
15. CPS-2

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REFERENCE:- 1. Pankaja Naik- Biochemistry; 4^th edition; page no:- 329-331.