Ribose-5-phosphate isomerase (RPIA (for type A isoform), RPIB (for type B isoform))

Ribose-5-phosphate isomerase is a highly conserved enzyme (EC 5.3.1.6) that catalyzes the reversible conversion between ribose-5-phosphate and ribulose-5-phosphate, a critical reaction in the non-oxidative branch of the pentose phosphate pathway and the Calvin cycle. This enzyme is ubiquitous in all domains of life. In prokaryotes (e.g., *Escherichia coli*), two active forms exist: the well-studied RpiA and the distantly related RpiB, which have different protein folds and catalytic residues but similar functions. The enzyme aids in carbohydrate metabolism, nucleotide biosynthesis, and regulation of cellular redox status. Pathogenic trypanosomatids rely on this enzyme, and its inhibition is being explored for treatment of certain parasitic diseases. In humans, deficiency of ribose-5-phosphate isomerase due to inactivating mutations can cause a rare, severe metabolic disorder. Structurally, the enzyme forms homo-dimers or tetramers and uses acid-base catalysis involving opening of the ribose ring, formation of an enediolate intermediate, and isomerization to the ketose form. There are currently no approved drugs specifically targeting the human enzyme, but selective inhibitors for the pathogen isoforms are of research interest.

Other names

D-ribose-5-phosphate aldose-ketose-isomeraseRpiA (type A isomerase, gene symbol)RpiB (type B isomerase, alternative gene)Ribose-5-phosphate isomerase ARibose-5-phosphate isomerase B

Enzyme inhibitors block isomerization of ribose-5-phosphate and ribulose-5-phosphate, potentially disrupting the pentose phosphate pathway and thus nucleotide synthesis and NADPH production in pathogens. Proposed mechanisms usually involve covalent or non-covalent active site binding, interfering with substrate conversion and enzyme function.