Difference Between Purine and Pyrimidine Synthesis

The key difference between purine and pyrimidine synthesis is that purine synthesis occurs mainly via salvage pathway while pyrimidine synthesis occurs mainly via De novo pathway.

Purine and pyrimidine are nitrogen-containing bases. Purines have a six-membered and a five-membered nitrogen-containing ring fused to each other. Pyrimidines have only a six-membered nitrogen-containing ring. Purines and pyrimidines are major parts of nucleotides which are building blocks of nucleic acids: DNA and RNA. Moreover, ATP is the energy currency, while UTP and GTP are also energy sources. Therefore, purines and pyrimidines are major energy carriers. They are precursors for the synthesis of nucleotide cofactors such as NAD. Purines and pyrimidines are synthesized via two principal routes: salvage and De novo pathways. In the salvage pathway, purines and pyrimidines are synthesized from intermediates from the degradative pathways. In De novo pathway, purines and pyrimidines are synthesized from the simple molecules, especially from amino acid precursors.

CONTENTS

1. Overview and Key Difference
2. What is Purine Synthesis
3. What is Pyrimidine Synthesis
4. Similarities Between Purine and Pyrimidine Synthesis
5. Side by Side Comparison – Purine vs Pyrimidine Synthesis in Tabular Form
6. Summary

What is Purine Synthesis?

Purines are two carbon nitrogen ring bases. They consist of a six-membered and a five-membered nitrogen-containing ring fused together. There are four purine bases. Adenine and guanine are two purines involved in the formation of nucleotides for nucleic acids. Hypoxanthine and xanthine are the other two purines which do not participate in nucleotides but are important for the synthesis and degradation of purine nucleotides.

Purines are synthesized as ribonucleotides. Purine synthesis takes place via both salvage and De novo pathways. In De novo pathway, IMP is the first product formed, and then it converts into either AMP or GMP. De novo pathway uses the entire glycine molecule (atoms 4, 5, 7), the amino nitrogen of aspartate (atom 1), amide nitrogen of glutamine (atoms 3, 9), components of the folate-one-carbon pool (atoms 2, 8), carbon dioxide, ribose 5-P from glucose and energy from ATP. Purine synthesis via the salvage pathway takes place with the use of 5-Phosphoribosyl-1-pyrophosphate (PRPP). The enzyme called phosphoribosyltransferases (PRT) catalyzes the salvaging of purines.

What is Pyrimidine Synthesis?

Pyrimidines are one carbon-nitrogen ring bases. They contain only a six-membered nitrogen-containing ring. There are four pyrimidines as thymine, uracil, cytosine and orotic acid. Uracil is found only in RNA. Cytosine is found in both DNA and RNA while thymine is found only in DNA. Similar to purine synthesis, pyrimidine synthesis also happens via both salvage and de novo pathways.

Pyrimidine De novo synthesis is simpler than purine synthesis since pyrimidine molecules are simple. Glutamine’s amide nitrogen and carbon dioxide provide atoms 2 and 3 of the pyrimidine ring. Other four atoms of the ring are supplied by aspartate. PRPP supplies the sugar-phosphate portion of the molecule. Salvaging pyrimidines is catalyzed by nucleoside phosphorylases (uridine phosphorylase and deoxythymidine phosphorylase) and nucleoside kinases (thymidine kinase and uridine kinase).

What are the Similarities Between Purine and Pyrimidine Synthesis?

• Both purine and pyrimidines are synthesized as nucleotides.
• Purine and pyrimidine synthesis occur via salvage and De novo.
• In De novo synthesis for both purine and pyrimidine synthesis, the sugar-phosphate portion of the molecule is supplied by PRPP.
• Humans mainly depend on the endogenous synthesis of purines and pyrimidines.
• Glutamine and aspartate are two amino acid precursors needed for de novo synthesis of both nucleotides.

What is the Difference Between Purine and Pyrimidine Synthesis?

Purine synthesis mainly occurs via the salvage pathway, while pyrimidine synthesis occurs mainly via the de novo pathway. So, this is the key difference between purine and pyrimidine synthesis. Moreover, pyrimidine synthesis is much simpler than purine synthesis since pyrimidine is a simple molecule than purine.

Gurthermore, glycine is an amino acid precursor for purine synthesis, while glycine does not involve in pyrimidine synthesis.

Below infographic tabulates side-by-side the differences between purine and pyrimidine synthesis.

Summary – Purine vs Pyrimidine Synthesis

Purines and pyrimidines are two kinds of nitrogen-containing bases. Both are important molecules which are synthesized as nucleotides via both salvage and de novo pathways. Most purines are synthesized via salvage pathway while most pyrimidines are synthesized de novo. Moreover, pyrimidine synthesis is much simpler than purine synthesis. PRPP is required for both purine and pyrimidine synthesis. Thus, this summarizes the difference between purine and pyrimidine synthesis.

Reference:

1. Moffatt, Barbara A, and Hiroshi Ashihara. “Purine and Pyrimidine Nucleotide Synthesis and Metabolism.” The Arabidopsis Book, American Society of Plant Biologists, 2002, Available here.
2. “Purine and Pyrimidine Metabolism.” Library – University of Utah. Available here.

Image Courtesy:

1. “Nucleotide synthesis” By Kelvinsong – Own work (CC0) via Commons Wikimedia
2. “Pyrimidine Synthesis V.2” By Jü – Own work (CC BY-SA 4.0) via Commons Wikimedia