Biochemistry at The Biology Project

B12/Folate Problem set

Question 5: Folate in the synthesis of DNA

Tutorial to help answer the question

Folate derivatives are required for the synthesis of which DNA nucleotides?

A. adenylate and guanylate
B. cytidylate and thymidylate
C. all four nucleotides
D. thymidylate only
E. adenylate, guanylate, and thymidylate


Three out of four

By way of review:

NucleotideType of basePresent inFolate form required
Adenylate (AMP or dAMP) Purine RNA or DNA N10-formyl THF
N5, N10-methenyl THF
Guanylate (GMP or dGMP) Purine RNA and DNA N10-formyl THF
N5, N10-methenyl THF
Cytidylate (CMP or dCMP) Pyrimidine RNA and DNA [none]
Uridylate (UMP only) Pyrimidate RNA only [none]
Thymidylate (dTMP only) Pyrimidine DNA only N5, N10-methylene THF

Fig. 5 - Folate needed for all purines plus thymidylate

Purines and pyrimidines each have common biosynthetic pathways, with the individual bases being formed by terminal modifications. In the purine pathway, N5, N10-methenyl THF are needed early on and are thus required for all purines (even ones like IMP that are not contained in DNA/RNA). After their utilization in purine biosynthesis, both N5, N10-methenyl THF and N10-formyl THF are recycled as THF (see figure above). Pyrimidines, on the other hand, do not require folate for the "core" biosynthetic reactions. It is only the very terminal step in the formation of dTMP that requires folate in the form of N5,N10-methylene THF. More about this reaction in the next question...

[Problem 5] [Answer] [Problem 6]

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