5-Phosphoribosyl -1 -pyrophosphate PRPP

Figure 10-2. Regulation of purine synthesis by the nucleotides and the intermediate, 5 -phosphoribosyl-1 -pyrophosphate (PRPP). Both feedback and feed-forward mechanisms are utilized in this intricate scheme. IMP, inosine monophosphate.

Synthesis of 5-phosphoribosyl-1-pyrophosphate (PRPP), showing the activator and inhibitors of the reaction. 

Parry, R.J. et al. Synthesis of 1 a-Pyrophosphoryl-2 a.3 a-dihydroxy-4/3-cyclopentanemethanol-5-phosphate, a Carbocyclic Analog of 5-Phosphoribosyl-1-pyrophosphate (PRPP). 2.1 1993 [168]... 

Figure 25.1. Salvage and de Novo Pathways. In a salvage pathway, a base is reattached to a ribose, activated in the form of 5-phosphoribosyl-1-pyrophosphate (PRPP). In de novo synthesis, the base itself is synthesized from simpler starting materials, including amino acids. ATP hydrolysis is required for de novo synthesis.

The crystal structure of hypoxanthine phosphoribosyltransferase has been solved in a ternary complex of the enzyme with the substrate 5-phosphoribosyl 1-pyrophosphate (PRPP) and an analogue of hypoxanthine with a carbon atom in place of As with PNP and OPRTase, these structures showed many contacts with... 

Figure 1 compares the levels of phosphoribosyltransfer activities in extracts of Rhesus monkey liver, L. donovani, and T. vaginalis. Magnesium 5-phosphoribosyl-1-pyrophosphate (PRPP) was the phosphoribosyl donor. Leishmania had high levels with adenine, hypoxanthine, guanine, and xanthine relative to those in monkey... 

Since intracellular 5-phosphoribosyl-1-pyrophosphate (PRPP) concentration limits purine biosynthesis de novo and is also a substrate in the reutilization pathways for purine bases we assessed PRPP levels and PRPP "generation" in erythrocytes after oral administration and during constant rate infusion of varying xylitol doses. 

The first step of the biosynthesis of pyrimidine nucleotides is the irreversible carbamylation of L-aspartate by carbamyl-phosphate to form carbamylaspartate (catalyzed by the enzyme aspartate transcarbamylase). Next, carbamylaspartate is converted, by ring closure, to dihydro-orotic acid which, in turn, is reduced to orotic acid, catalyzed by the enzyme orotic acid dehydrogenase (OAD). Orotic acid (6-carboxyuracil) reacts with 5 -phosphoribosyl--1-pyrophosphate (PRPP) to form orotidine monophosphate (OMP). 

Non- oxidative branch Pentose-5 -Phosphates Ribose-5-P 2 deoxy ribose-5-P 5 -phosphoribosyl-1 -pyrophosphate (PRPP) i) Structural components of nucleotides a. Basal structural component of RNA b. Basal structural component of DNA c. Precursor of both de novo and salvage synthesis of nucleotides ii) Intermediate products of purine metabolism and act as precursor molecules of cofactors, e g., riboflavin, flavin mononucleotide (FMN), flavin adenine di nucleotide (FAD) iii) Precursor of the amino acid. Histidine. 

It has been established in earlier investigations >2 that the synthesis of purine nucleotides in mammalian red blood cells (RBC) is governed by the extent of endogenous supply of 5-phosphoribosyl-1-pyrophosphate (PRPP), as an essential intermediary. Consequently, the elucidation of the mechanisms controlling the formation of PRPP within the cell appears to be of crucial importance for the understanding of the overall metabolic regulation of purine nucleotide biosynthesis. 

Addition of 5-phosphoribosyl-1-pyrophosphate (PRPP) to normal and LNS dialyzed hemolysates resulted in stabilization of APRT to heat Inactivation. Under these conditions APRT in both normal and LNS hemolysates attained the same degree of stability (approximately 95 residual activity). 

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