Ribose-5-phosphate isomerase

Ribose-5-phosphate isomerase (Rpi) encoded by the RPIA gene is an enzyme that catalyzes the conversion between ribose-5-phosphate (R5P) and ribulose-5-phosphate (Ru5P). It is a member or a larger class of isomerases which catalyze the interconversion of chemical isomers (in this case structural isomers of pentose). It plays a vital role in biochemical metabolism in both the pentose phosphate pathway and the Calvin cycle. The systematic name of this enzyme class is D-ribose-5-phosphate aldose-ketose-isomerase. Ribose-5-phosphate isomerase (Rpi) encoded by the RPIA gene is an enzyme that catalyzes the conversion between ribose-5-phosphate (R5P) and ribulose-5-phosphate (Ru5P). It is a member or a larger class of isomerases which catalyze the interconversion of chemical isomers (in this case structural isomers of pentose). It plays a vital role in biochemical metabolism in both the pentose phosphate pathway and the Calvin cycle. The systematic name of this enzyme class is D-ribose-5-phosphate aldose-ketose-isomerase. RpiA in human beings is encoded on the second chromosome on the short arm (p arm) at position 11.2. Its encoding sequence is nearly 60,000 base pairs long. The only known naturally occurring genetic mutation results in ribose-5-phosphate isomerase deficiency, discussed below. The enzyme is thought to have been present for most of evolutionary history. Knock-out experiments conducted on the genes of various species meant to encode RpiA have indicated similar conserved residues and structural motifs, indicating ancient origins of the gene. Rpi exists as two distinct proteins, termed RpiA and RpiB. Although RpiA and RpiB catalyze the same reaction, they show no sequence or overall structural homology. According to Jung et al., an assessment of RpiA using SDS-PAGE shows that the enzyme is a homodimer of 25 kDa subunits. The molecular mass of the RpiA dimer was found to be 49 kDa by gel filtration. Recently, the crystal structure of RpiA was determined. (please see http://www3.interscience.wiley.com/cgi-bin/fulltext/97516673/PDFSTAR) Due to its role in the pentose phosphate pathway and the Calvin cycle, RpiA is highly conserved in most organisms, such as bacteria, plants, and animals. RpiA plays an essential role in the metabolism of plants and animals, as it is involved in the Calvin cycle which takes place in plants, and the pentose phosphate pathway which takes place in plants as well as animals. All orthologs of the enzyme maintain an asymmetric tetramer quaternary structure with a cleft containing the active site. Each subunit consists of a five stranded β-sheet. These β-sheets are surrounded on both sides by α-helices. This αβα motif is not uncommon in other proteins, suggesting possible homology with other enzymes. The separate molecules of the enzyme are held together by highly polar contacts on the external surfaces of the monomers. It is presumed that the active site is located where multiple β-sheet C termini come together in the enzymatic cleft. This cleft is capable of closing upon recognition of the phosphate on the pentose (or an appropriate phosphate inhibitor). The active site is known to contain conserved residues equivalent to the E. coli residues Asp81, Asp84, and Lys94. These are directly involved in catalysis. In the reaction, the overall consequence is the movement of a carbonyl group from carbon number 1 to carbon number 2; this is achieved by the reaction going through an enediol intermediate (Figure 1). Through site-directed mutagenesis, Asp87 of spinach RpiA was suggested to play the role of a general base in the interconversion of R5P to Ru5P. The first step in the catalysis is the docking of the pentose into the active site in the enzymatic cleft, followed by allosteric closing of the cleft. The enzyme is capable of bonding with the open-chain or ring form of the sugar-phosphate. If it does bind the furanose ring, it next opens the ring. Then the enzyme forms the eneldiol which is stabilized by a lysine or arginine residue. Calculations have demonstrated that this stabilization is the most significant contributor to the overall catalytic activity of this isomerase and a number of others like it. The protein encoded by RPIA gene is an enzyme, which catalyzes the reversible conversion between ribose-5-phosphate and ribulose-5-phosphate in the pentose-phosphate pathway. This gene is highly conserved in most organisms. The enzyme plays an essential role in the carbohydrate metabolism. Mutations in this gene cause ribose 5-phosphate isomerase deficiency. A pseudogene is found on chromosome 18.