In the 1850s, Louis Pasteur concluded that fermentation of sugar into alcohol by yeast is catalyzed by "ferments". Then in 1897 Eduard Buchner discovered that yeast extracts could ferment sugar to alcohol providing that fermentation was performed by molecules which continued to function when removed from cells…
Others require an additional chemical component called a cofactor such as an inorganic ion Fe2+, Mg2+, Zn2+ or a metalloorganic molecule called a coenzyme. (Lehninger 4th Edition)
Enzymes are classified into six classes each with sub classes based on the type of reaction catalyzed. Thus our enzyme of interest Phosphoribosylpyrophosphate (PRPP) Synthetase (Prs) belongs to the class Transferases catalyzing group transfer reactions with its Enzyme Commission Number as 18.104.22.168. (Online Mendelian Inheritance in Man, 2010)
Phosphoribosylpyrophosphate synthetase (Prs) (or Ribose-phosphate diphosphokinase) catalyses the synthesis of phosphoribosyl pyrophosphate (PRPP), an intermediate in nucleotide metabolism for the de novo and salvage pathways of purine and pyrimidine biosynthesis and the biosynthesis of the amino acids histidine and tryptophan.
One of the important specialized pathways of a number of amino acids is the synthesis of purine and pyrimidine nucleotides. The two ringed purine members Adenine, Guanine, Hypoxanthine and Xanthine and the single ringed pyrimidines namely Cytosine, Thymine, Uracil are important for a number of reasons. Most of them, not just ATP, are the sources of energy that drive most of our reactions. ATP is the most commonly used source but GTP is used in protein synthesis as well as a few other reactions. UTP is the source of energy for activating glucose and galactose. CTP is an energy source in lipid metabolism. AMP is part of the structure of some of the coenzymes like NAD and Coenzyme A. We can both synthesize them de novo and salvage and reuse those we already have.(Angstadt 1997)
Metabolic contribution of PRPP to the purine biosynthesis and other anabolic pathways
Source: Taken and Adapted from BMC Biotechnology (Jimenez 2008)
PRPP, synthesized from ribose-5-phosphate and ATP, is therefore a key compound for purine biosynthesis, and it is also an important cellular metabolite because it represents a link between carbon and nitrogen metabolism. PRPP is a biosynthetic precursor of histidine and tryptophan, and it is also required for the de novo and salvage pathways of purine, pyrimidine and pyridine (NAD+, NADP+) nucleotides. It has been calculated that approximately 80% of the metabolic flux through PRPP is directed to purine and pyrimidine synthesis
The formation of PRPP is catalyzed by the enzyme PRPP synthetase which is encoded by PRS genes
Pathway of Purine nucleotide synthesis and its regulation by PRPP. Taken and adapted from (Becker, Kim et al. 1992)
The PRPP is further committed to de novo purine nucleotide synthesis in a 10 step enzymatic reaction as follows:
Taken From Rolfes 2006
This essay will examine the reactions that take place during the PRPP pathways and the synthesis of purine nucleotide. In microbes such as Escherichia coli and Saccharomyces cerevisiae, the inability to biosynthesize purine nucleotides leads to auxotrophy. In Drosophila, purine nucleotide synthesis is required for development and metamorphosis. In plants such as Arabidopsis and tobacco (Nicotiana tabacum), synthesis of nucleotides is developmentally regulated, whereas in the tropical legumes it plays an additional important role in nitrogen storag. In humans, disorders in the purine nucleotide biosynthetic and salvage pathways have devastating consequences, leading to disorders such as SCIDS (severe combined immunodeficiency syndrome), ...
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