Question

Folate is required for the normal DNA synthesis. Folate deficiency impairs the activity of the folate requiring enzyme synthase and thus the synthesis of which nucleotide is decreased.

• A. dATP
• B. dCTP
• C. dTTP
• D. dGTP

Hint:

To remember this key metabolic block:
- Thymidylate Synthase is the only enzyme that converts Uracil-like nucleotides (dUMP) to Thymine nucleotides (dTMP).
- This conversion is strictly dependent on Folate as a methyl donor.
- Blocking this step selectively depletes dTTP, halting DNA replication.

Answer 1

The Correct Option is C

Step 1: Understanding the Concept:
Tetrahydrofolate (THF) is a biologically active form of folate that serves as a carrier of one-carbon units in various metabolic pathways.
These pathways include amino acid metabolism and the de novo synthesis of purine and pyrimidine nucleotides.

Step 2: Detailed Explanation:
The synthesis of the pyrimidine nucleotide thymidine triphosphate (dTTP) requires a critical, folate-dependent enzymatic step:
The enzyme thymidylate synthase catalyzes the conversion of dUMP (deoxyuridine monophosphate) to dTMP (deoxythymidine monophosphate) by transferring a methyl group.
The coenzyme required for this reaction is \(\text{N}^5,\text{N}^{10}\)-methylene tetrahydrofolate, which acts as both the one-carbon donor and the reducing agent.
Once dTMP is synthesized, it is sequentially phosphorylated by kinases to dTDP and finally to dTTP (C).
dTTP is one of the four essential deoxyribonucleoside triphosphates required as a precursor for DNA replication.
In folate deficiency, the availability of \(\text{N}^5,\text{N}^{10}\)-methylene tetrahydrofolate is severely limited.
This impairs the activity of thymidylate synthase, blocking the conversion of dUMP to dTMP.
As a result, the synthesis of dTTP decreases significantly.
Because the other three nucleotides—dATP (A), dCTP (B), and dGTP (D)—do not rely directly on this specific rate-limiting folate methylation pathway, their synthesis is not as selectively blocked.
This imbalance (lack of dTTP) leads to the misincorporation of uracil into DNA, resulting in DNA damage, cell cycle arrest, and megaloblastic anemia.

Step 3: Final Answer:
Folate deficiency directly impairs the synthesis of the nucleotide dTTP.