Pentose phosphate pathway

A reusable central-carbon module for the pentose phosphate pathway, covering the oxidative conversion of glucose 6-phosphate to ribulose 5-phosphate, the non-oxidative interconversion of pentose phosphates with fructose 6-phosphate and glyceraldehyde 3-phosphate, and the activation of ribose 5-phosphate to 5-phospho-alpha-D-ribose 1-diphosphate (PRPP). The oxidative branch generates NADPH through glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, with 6-phosphogluconolactonase hydrolyzing the intermediate lactone; its first step is irreversible and rate-limiting. The reversible non-oxidative branch uses ribose-5-phosphate isomerase, ribulose-phosphate 3-epimerase, transketolase, and transaldolase to balance ribose 5-phosphate, xylulose 5-phosphate, sedoheptulose 7-phosphate, erythrose 4-phosphate, fructose 6-phosphate, and glyceraldehyde 3-phosphate according to the demand for NADPH, nucleotide precursors and glycolytic intermediates. Ribose 5-phosphate leaves the pathway mainly through ribose-phosphate diphosphokinase, whose product PRPP feeds nucleotide, histidine and tryptophan biosynthesis. In eukaryotes the pathway is cytosolic. Yeast and bacterial proteins are used as concrete exemplars.

ALIGN (YeastPathways project, 2026-10): the module, first built from P. putida KT2440, was generalized to the conserved PPP and given S. cerevisiae and S. pombe exemplars for every step, plus the PRPP-synthesis exit (YeastCyc PWY0-662), which the crosswalk places in scope. All annotons are given a cytosolic location (all yeast and human PPP enzymes are cytosolic). The human disease-oriented split modules pentose_phosphate_oxidative_branch and pentose_phosphate_nonoxidative_branch are left unchanged; note that human TKT sits in PANTHER PTHR43195 whereas yeast, S. pombe and bacterial transketolases fall in PTHR43522, so the transketolase role here keeps PTHR43522. YeastCyc corrections: GND1/GND2 added to RXN-9952 (no gene in YeastCyc; PMID:1328471); TKL2 added to 2TRANSKETO-RXN (the tkl1 tkl2 double mutant, not tkl1 alone, lacks erythrose 4-phosphate, PMID:7916691); NQM1 added as a minor transaldolase. SOL1 and SOL2 are deliberately excluded: they are Sol-family paralogs without detectable lactonase activity (PMID:15454531). S. pombe has a second G6PD-family protein (SPAC3C7.13c) that the PomBase GO-CAM also annotates with GO:0004345, and a Gcd1 glucose dehydrogenase (also PTHR23429) that, with Idn1 gluconate kinase, forms a gluconate shunt into 6-phosphogluconate bypassing G6PD (PMID:28667014); both are recorded here as adjacent biology rather than modelled, and only zwf1 is used as the S. pombe G6PD exemplar. Boundary decision for PSEPK ppu00030: glucose/gluconate oxidation, Entner-Doudoroff dehydratase and aldolase, lower glycolysis, and phosphoglucomutase remain adjacent modules or exits; the 6-phosphogluconate branch point to ED is recorded without pulling ED enzymes into the module. The KT2440 G6PDH family has paralogs; zwfA and zwfB are the main bacterial exemplars, while PP_5351/zwfC is a condition-specific paralog. The five yeast PRS proteins act as heteromeric complexes (PMID:10212224); they are modelled as a family role rather than as a complex because subunit stoichiometry is unresolved. GO-CAM disagreements: the three YeastPathways models agree with the module (they already include GND1/GND2 and SOL3/SOL4) except that the PENTOSE-P-PWY and NONOXIPENT-PWY models give TKL2 only the first transketolase reaction. The PomBase model 67b1629100000953 also contains gcd1, idn1, rbk1 ribokinase, tnr3 thiamine diphosphokinase and pgi1, which are outside this module, and has no PRPP-synthase activity.