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Phosphoribosyl Diphosphate (PRPP): Biosynthesis, Enzymology, Utilization, and Metabolic Significance
Bjarne Hove-Jensen1,2, Kasper R Andersen2, Mogens Kilstrup3
1DTU Systems Biology, Technical University of Denmark, Kongens Lyngby, Denmark hove@mbg.au.dk.
Microbiology and Molecular Biology Reviews : MMBR
|December 30, 2016
Summary
Phosphoribosyl diphosphate (PRPP) is a vital metabolic intermediate synthesized by PRPP synthase. Its diverse roles in biosynthesis and regulation highlight its central importance in cellular physiology across all life forms.
Area of Science:
- Biochemistry
- Molecular Biology
- Enzymology
Background:
- Phosphoribosyl diphosphate (PRPP) is a crucial intermediate in cellular metabolism.
- It is synthesized by PRPP synthase and involved in numerous biosynthetic pathways.
Purpose of the Study:
- To review the metabolic pathways involving PRPP.
- To unify classical mechanistic studies with recent molecular enzymology and structural data of PRPP synthases.
- To explore the evolutionary origins and regulatory roles of PRPP.
Main Methods:
- Classical mechanistic procedures for studying PRPP synthase.
- Molecular enzymology and determination of 3D structures of PRPP synthases.
- Phylogenetic analysis and genetic studies of PRPP synthase genes.
Main Results:
- PRPP participates in the biosynthesis of nucleotides, amino acids, cofactors, and antibiotics.
- PRPP synthases from eubacteria, archaea, and humans share conserved structures and catalytic mechanisms.
- PRPP acts as a metabolic effector, regulating nucleotide biosynthesis through regulatory proteins and allosteric activation.
Conclusions:
- PRPP is a versatile intermediate with essential roles in cellular physiology.
- PRPP synthases evolved from phosphoribosyltransferases.
- Understanding PRPP metabolism and its synthases is crucial for comprehending cellular function and potential therapeutic targets.
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