Nucleotides are essential building blocks of nucleic acids—DNA and RNA—and serve numerous other cellular functions. Their biosynthesis occurs via two primary pathways: the de novo pathway, which builds nucleotides from simple precursors, and the salvage pathway, which recycles free bases and nucleosides. Understanding the de novo synthesis of purine and pyrimidine nucleotides is fundamental to biochemistry and molecular biology.

This article examines four common statements related to de novo nucleotide biosynthesis and identifies which one is incorrect based on current scientific knowledge.

Statement 1: Starting Point of Purine and Pyrimidine Biosynthesis

• Both purine and pyrimidine nucleotide biosynthesis pathways begin with ribose-5-phosphate.

• Ribose-5-phosphate is converted to phosphoribosyl pyrophosphate (PRPP) by PRPP synthetase.

• In purine biosynthesis, the purine ring is built directly on the ribose sugar attached to PRPP.

• In pyrimidine biosynthesis, the pyrimidine ring is synthesized first as orotate, which is then attached to ribose phosphate.

• Therefore, the statement that both pathways begin with ribose-5-phosphate and build the ring on it is correct.

Statement 2: First Purine Nucleotide Synthesized

• The first purine nucleotide formed by the de novo pathway is inosine monophosphate (IMP), also called inosinic acid.

• IMP serves as the precursor for both adenine and guanine nucleotides.

• This statement is correct.

Statement 3: First Pyrimidine Nucleotide Synthesized

• The first pyrimidine nucleotide synthesized is orotidine monophosphate (OMP) or orotidylic acid.

• OMP is formed by attaching orotate to PRPP.

• OMP is then decarboxylated to form uridine monophosphate (UMP), the precursor for other pyrimidine nucleotides.

• This statement is correct.

Statement 4: Synthesis of Thymidylate (TMP)

• Thymidylate (TMP) is an essential pyrimidine nucleotide found in DNA.

• TMP is synthesized by methylation of deoxyuridine monophosphate (dUMP), catalyzed by thymidylate synthase.

• The precursor is dUMP, not deoxy-UMP (a non-standard term).

• TMP is not synthesized directly as deoxy-TMP from deoxy-UMP; rather, dUMP is methylated to form dTMP.

• The statement as given is incorrect because it implies TMP is synthesized from deoxy-UMP by thymidylate synthetase in a manner that is not standard terminology or pathway description.

Summary Table

Conclusion

The incorrect statement among the options regarding de novo nucleotide biosynthesis is:

(4) Thymidylate or TMP is synthesized as deoxy-TMP from deoxy-UMP by thymidylate synthetase.