Phosphopentose epimerase (also known as ribulose-phosphate 3-epimerase and ribulose 5-phosphate 3-epimerase, EC 5.1.3.1) encoded in humans by the RPE gene[1] is a metalloprotein that catalyzes the interconversion between D-ribulose 5-phosphate and D-xylulose 5-phosphate.

[2] This reversible conversion is required for carbon fixation in plants – through the Calvin cycle – and for the nonoxidative phase of the pentose phosphate pathway.

This enzyme belongs to the isomerase family, specifically those racemases and epimerases which act on carbohydrates and their derivatives.

[2] In addition, the Structural Classification of Proteins database has defined the “ribulose phosphate binding” superfamily for which this epimerase is a member.

[3] However, human phosphopentose epimerase – which is encoded by the RPE gene - differs in that it binds Fe2+ predominantly in catalysis.

Mutagenesis studies have also indicated that two aspartic acids are located within the active site and help mediate catalysis through a 1,1-proton transfer reaction.

Electron microscopy experiments in plants have shown that phosphopentose epimerase localizes to the thylakoid membrane of chloroplasts.

RuBP is the acceptor of the carbon dioxide (CO2) in the first step of the pathway, which suggests that phosphopentose epimerase regulates flux through the Calvin cycle.

Phosphopentose epimerase specifically affects the nonoxidative portion of the pathway, which involves the production of various sugars and precursors.

Due to its involvement in this pathway, phosphopentose epimerase is an important enzyme for the cellular response to oxidative stress.

[3] The generation of NADPH by the pentose phosphate pathway helps protect cells against reactive oxygen species.

It is important to note that the members of the “ribulose phosphate binding” superfamily resulted from divergent evolution from a (β/α)8 - barrel ancestor.

Due to this enzyme’s involvement in the shikimate pathway, phosphopentose epimerase is a potential drug target for developing antimalarials.