t NADPH and the pentose Ru5P. NADPH is required for the reductive biosynthesis of fatty acids and cholesterol, cellular antioxidation (reduction of glutathione from its oxidized form by glutathione reductase) and superoxide generation (substrate of NADPH oxidase). Ru5P is epimerized to Xu5P or isomerized to R5P by the action of Rpe and Rpia, respectively. R5P is a precursor for nucleotide and nucleic acid synthesis. If the need for NADPH exceeds the need for R5P, Xu5P and R5P are formed in a ratio of 2:1 and metabolized to GAP and F6P via three reversible reactions involving carbon-carbon cleavage and transfer of C₂ and C₃ units. GAP and F6P are intermediates in the glycolytic and gluconeogenic pathway; they can be diverted back to R5P in the reverse reactions of the non-oxidative phase if the need for R5P increases (note the directionality of arrows). In the first and rate-limiting step of the oxidative phase, G6P is dehydrogenated by G6pd to produce the first NADPH and 6-phosphogluconolactone which is rapidly and irreversibly hydrolyzed to 6-phosphoglucone. This product is oxidatively decarboxylated to yield the second NADPH and Ru5P. The second and third reactions of the oxidative phase are carried out by Pgls and Pgd, respectively. The first reaction of the non-oxidative phase involves the conversion of Ru5P to Xy5P and R5P. If the non-oxidative phase proceeds, transketolase catalyzes the transfer of a C₂ unit from Xu5P to R5P yielding GAP and S7P. A C₃ unit is transferred from S7P to GAP in the reaction catalyzed by transaldolase to yield E4P and F6P. A C₂ unit is transferred from a second Xu5P to E4P to yield GAP and a second F6P molecule, a reaction also catalyzed by transketolase. Transketolase use thiamine pyrophosphate as a co-factor. The carbon-carbon rearrangements underlie the pentose (Ru5P) to hexose (F6P) transformation. Despite the importance of the PPP in a number of cellular processes and its position at the crossroads of many metabolic pathways, little is known about how the pathway is regulated. Alterations in PPP components have been linked to several conditions. To see the ontology report for annotations, GViewer and download, click here
[Click here to see the ontology report for associated GO term - GO:0006098, KEGG map - map00030 and entry at Reactome]...(less)