Difference Between De Novo and Salvage Pathway

The key difference between de novo and salvage pathway is that de novo synthesis of purine nucleotides refers to the process that utilizes small molecules such as phosphoribose, amino acids, CO₂ etc. as raw materials to produce purine nucleotides, while salvage pathway of purine synthesis refers to the process that utilizes purine bases and purine nucleosides in order to produce purine nucleotides.

Nucleotides are the building blocks of nucleic acids. Moreover, some nucleotides, especially ATP, have an important role in energy transfer. Some work as secondary messengers as well. A nucleotide has three components: a sugar, a nitrogen base and a phosphate group. Synthesis of nucleotides takes place via different pathways. De novo pathway and salvage pathway are two main pathways of synthesis of purine nucleotides. De novo pathway acts as the main pathway while salvage pathway is important for purine nucleotide synthesis in the brain and bone marrow. Therefore, the de novo pathway is a major pathway while salvage pathway is a minor pathway.

CONTENTS

1. Overview and Key Difference
2. What is De Novo Pathway
3. What is Salvage Pathway
4. Similarities Between De Novo and Salvage Pathway
5. Side by Side Comparison – De Novo vs Salvage Pathway in Tabular Form
6. Summary

What is De Novo Pathway?

De novo pathway is a metabolic pathway that begins with small molecules and synthesizes new complex molecules. Thus, de novo synthesis of purine nucleotides refers to the process that utilizes small molecules to produce purine nucleotides. It uses raw materials such as phosphoribose, amino acids (glutamine, glycine, and aspartate), CO_2, etc., to synthesize purine nucleotides. Moreover, the de novo pathway is the main pathway that synthesizes purine nucleotides.

In de novo pathway, ribose -5-phosphate works as the starting material. Then, it reacts with ATP and converts into phosphoribosyl pyrophosphate (PRPP). Next, glutamine donates its amide group to PRPP and converts it to 5-phosphoribosylamine. Thereafter, the 5-phosphoribosylamine reacts with glycine and becomes glycinamide ribosyl 5-phosphate, and later, it converts into formylglycinamide ribosyl 5-phosphate. Glutamine donates its amide group and converts formylglycinamide ribosyl 5-phosphate into formylglycinamideine ribosyl 5-phosphate. Then the imidazole ring of the purine completes its ring form. Finally, with the incorporation of CO₂ and undergoing several further reactions, it becomes the inosine monophosphate (IMP). IMP is the immediate precursor molecule of the adenosine monophosphate (AMP) and guanosine monophosphate (GMP), which are purine nucleotides.

What is Salvage Pathway?

Salvage pathway of purine nucleotide synthesis refers to the process of synthesizing nucleotides from purine bases and purine nucleosides. Purine bases and purine nucleotides are constantly produced in the cells as a result of the metabolism of nucleotides such as polynucleotide degradation. Moreover, these bases and nucleosides also enter our body by the food we consume.

Salvage pathway of purine nucleotide synthesis is a minor pathway. It occurs mainly by the phosphoribosyltransferase reaction. Two specific enzymes, adenine phosphoribosyl transferase (APRT) and hypoxanthine-guanine phosphoribosyl transferase (HGPRT), catalyze the phosphoribosyltransferase reaction. They catalyze the transfer of ribose-5’-phosphate moiety from phosphoribosyl pyrophosphate (PRPP) to purine bases to yield purine nucleotides. The salvage pathway is important in certain tissues where de novo synthesis is not possible.

What are the Similarities Between De Novo and Salvage Pathway?

• De novo and salvage are two pathways of nucleotide synthesis.
• Moreover, both assemble ribonucleotides that can be used to synthesise deoxyribonucleotides for DNA.
• Furthermore, feedback inhibition regulates both pathways.

What is the Difference Between De Novo and Salvage Pathway?

Nucleotide synthesis occurs via two pathways: de novo pathway and salvage pathway. De novo pathway utilizes small molecules to produce nucleotides, while salvage pathway utilizes preformed bases and nucleosides to produce nucleotides. So, this is the key difference between de novo and salvage pathway.

Furthermore, another significant difference between de novo and salvage pathway is that the de novo pathway occurs in all cell types while salvage pathway occurs in certain tissues where de novo process is not possible. Moreover, de novo pathway is the major pathway while salvage pathway is a minor pathway of nucleotide synthesis.

The below info-graphic shows more comparisons related to the another difference between de novo and salvage pathway.

Summary – De Novo vs Salvage Pathway

De novo pathway is a pathway of newly synthesizing complex compounds from small molecules. Salvage pathway is a pathway of utilizing previously made compounds in order to synthesize complex compounds. In nucleotide synthesis, both de novo and salvage pathways are seen. Thus, de novo pathway of purine nucleotide synthesis refers to the process that utilizes small molecules such as ribose sugar, amino acids, CO₂, one carbon unit, etc. to produce new purine nucleotides. On the other hand, salvage pathway of purine nucleotide synthesis refers to the process that utilizes previously made bases and nucleosides to produce purine nucleotides. Thus, this is the key difference between de novo and salvage pathway. Furthermore, all cell types have the ability to carry out de novo pathway while only certain tissues are able to carry out salvage pathway.

Reference:

1. “Purine Nucleotide.” Purine Nucleotide – an Overview | ScienceDirect Topics, Available here.
2. Nyhan, William L. “Nucleotide Synthesis via Salvage Pathway.” Wiley Online Library, American Cancer Society, 9 Dec. 2014, Available here.

Image Courtesy:

1. “Purine-de-novo” By Ayacop – Own work, Public Domain) via Commons Wikimedia
2. “HPRT metabolism” By Torres RJ, Puig JG – Torres RJ, Puig JG. Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency: Lesch-Nyhan Syndrome. Orphanet J Rare Dis. 2, 1. 2007. PMID 18067674. DOI:10.1186/1750-1172-2-48 (CC BY 3.0) via Commons Wikimedia