Reactome: A Curated Pathway Database

5-Phosphoribose 1-diphosphate biosynthesis (R-HSA-73843)

Species Homo sapiens

Summation

5-Phospho-alpha-D-ribose 1-diphosphate (PRPP) is a key intermediate in both the de novo and salvage pathways of purine and pyrimidine synthesis. PRPP and the enzymatic activity responsible for its synthesis were first described by Kornberg et al. (1955). The enzyme, phosphoribosyl pyrophosphate synthetase 1, has been purified from human erythrocytes and characterized biochemically. The purified enzyme readily forms multimers; its smallest active form appears to be a dimer and for simplicity it is annotated as a dimer here. It specifically catalyzes the transfer of pyrophosphate from ATP or dATP to D-ribose 5-phosphate, and has an absolute requirement for Mg++ and orthophosphate (Fox and Kelley 1971; Roth et al. 1974). The significance of the reaction with dATP in vivo is unclear, as the concentration of cytosolic dATP is normally much lower than that of ATP. The importance of this enzyme for purine synthesis in vivo has been established by demonstrating excess phosphoribosyl pyrophosphate synthetase activity, correlated with elevated enzyme levels or altered enzyme properties, in individuals whose rates of uric acid production are constitutively abnormally high (Becker and Kim 1987; Roessler et al. 1993).

Molecular cloning studies have revealed the existence of two additional genes that encode phosphoribosyl pyrophosphate synthetase-like proteins, one widely expressed (phosphoribosyl pyrophosphate synthetase 2) and one whose expression appears to be confined to the testis (phosphoribosyl pyrophosphate synthetase 1-like 1) (Taira et al. 1989; 1991). Neither of these proteins has been purified and characterized enzymatically, nor have variations in the abundance or sequence of either protein been associated with alterations in human nucleotide metabolism (Roessler et al. 1993; Becker et al. 1996), so their dimerization and ability to catalyze the synthesis of PRPP from D-ribose 5-phosphate are inferred here on the basis of their predicted amino acid sequence similarity to phosphoribosyl pyrophosphate synthetase 1.

Locations in the PathwayBrowser
Additional Information
Synonyms PRPP biosynthesis
Compartment cytosol
GO Biological Process 5-phosphoribose 1-diphosphate biosynthetic process (0006015)
Cross References
Database Identifier
BioModels Database BIOMD0000000015