Generic Embden-Meyerhof-Parnas (EMP) glycolysis module

Scope: direct entry at fructose 6-phosphate. Fructose phosphorylated at C6 by a broad-specificity hexokinase, and mannose phosphorylated to mannose 6-phosphate and isomerised by mannose-6-phosphate isomerase, both land on fructose 6-phosphate and are inside GO:0061615. They are modelled as the fructose_mannose_entry_variant of the entry step, which feeds the phosphofructokinase step directly and skips the glucose-6-phosphate isomerase step. Scope: the fructose-1-phosphate route is deliberately excluded. The bacterial fructose PTS yields fructose 1-phosphate, which 1-phosphofructokinase (FruK, EC 2.7.1.56) phosphorylates straight to fructose 1,6-bisphosphate, bypassing both the isomerase and the phosphofructokinase step — and therefore bypassing the fructose-6-phosphate intermediate that defines this module. GO treats that route the same way: GO:0061625 glycolytic process through fructose-1-phosphate is a SIBLING of this module's core term GO:0061615 under GO:0006096, not a child of it, so the route is outside this module rather than a missing variant of it. It is covered by modules/bacterial_fructose_pts_catabolism.yaml and modules/fructose_pts_uptake_and_catabolism.yaml. The glucose PTS variant retained here is a different thing: it yields glucose 6-phosphate and rejoins the F6P route at the isomerase. Scope. The module starts at hexose entry and ends at pyruvate. The fate of pyruvate (pyruvate dehydrogenase, lactate or ethanol fermentation, anaplerotic carboxylation), the reoxidation of the reduced cofactor produced at the oxidation step, and the mobilisation of glucans that feeds the glucose-1-phosphate entry variant are all deliberately outside it, and are covered by separate modules. Relationship to gluconeogenesis. Counting reactions rather than parts (the phosphorylating oxidation part contains two), the module has ten, of which seven are near-equilibrium and are shared, run in reverse, by the gluconeogenesis template. Only the entry kinase, the phosphofructokinase step (except in the diphosphate-dependent variant, which is freely reversible) and the pyruvate kinase step are effectively irreversible, and those three are exactly the steps the gluconeogenesis module covers with dedicated bypass reactions. The two modules are intended to be read together. Grounding. scope is ABSTRACT: every step is defined by its required GO molecular function, and the steps that fungi use are oriented by a PANTHER family with representative budding-yeast and fission-yeast members (for aldolase and phosphoglycerate mutase, both non-homologous enzyme families are named). The representatives are examples, not a complete list of members. The archaeal ADP-dependent kinases, the bacterial PTS, the diphosphate-dependent PFK and the non-phosphorylating or ferredoxin-dependent G3P oxidations have no yeast member and stay ungrounded ANY_WITH_FUNCTION selectors, so leaf-grounding QC gaps on those variants are expected. Concrete human grounding lives in glycolysis_investment_phase and glycolysis_payoff_phase; entner_doudoroff_and_gluconeogenesis is the bacterial contrast case. Yeast realisation (YeastPathways GLYCOLYSIS, PWY3O-3827, PWY3O-0, PWY3O-1743). On glucose the main isozymes are Hxk2 (hexokinase), Tdh3 (GAPDH, 50-60% of activity) and Cdc19 (pyruvate kinase), and PFK is the Pfk1/Pfk2 alpha4beta4 hetero-octamer. Hxk1, Glk1 and Pyk2 are glucose-repressed isozymes. Corrections relative to YeastCyc: (1) FBP1 is listed in the GLYCOLYSIS frame and its GO-CAM (F16BDEPHOS-RXN, part_of glycolysis) but is the gluconeogenic bypass enzyme and is not a member of this module; (2) GPM1 is assigned to both the dPGM (RXN-15513) and iPGM (3PGAREARR-RXN, EC 5.4.2.12) reactions, but Gpm1 is a dPGM, and only the former is used; (3) PWY3O-0 and its GO-CAM type Hxk1/Hxk2 on fructose as GO:0008865 fructokinase activity (EC 2.7.1.4). Hexokinases phosphorylate fructose with their own hexokinase activity (GO:0004396, EC 2.7.1.1), and that is the term used here. GO-CAM notes: the SGD glycolysis model has no hexokinase step (the frame starts at glucose 6-phosphate) and gives the PFK activity to complex CPX-554. The PomBase model 663d668500002302 covers all ten steps (hxk1/hxk2, pgi1, pfk1, fba1, tpi1, tdh1/gpd3, pgk1, gpm1, eno101/eno102, pyk1). It also holds activities outside this module (fbp26 fructose-2,6-bisphosphate turnover, ser3, pda1, mitochondrial pyruvate import) and lists tpi1 twice (663d668500002432 and 68b0f0d000002382). Stoichiometry. Per hexose entering at glucose 6-phosphate via an ATP-dependent kinase and running the phosphorylating oxidation variant: 2 ATP invested, 4 ATP and 2 NAD(P)H produced, for a net 2 ATP + 2 NAD(P)H + 2 pyruvate. The PTS entry variant substitutes one phosphoenolpyruvate for one investment ATP; the non-phosphorylating oxidation variants forgo 2 ATP per hexose; the diphosphate-dependent phosphofructokinase variant spends diphosphate rather than ATP. Ontology limitations recorded against this template. GO provides no molecular function term distinguishing cofactor-dependent (dPGM, EC 5.4.2.11) from cofactor-independent (iPGM, EC 5.4.2.12) phosphoglycerate mutase — GO:0046538 and GO:0046537 are obsolete with term_replaced_by GO:0004619 — and class I (Schiff-base) and class II (metal-dependent) fructose-bisphosphate aldolases likewise share GO:0004332 and EC 4.1.2.13. In both cases a concrete module cannot record which family an organism uses through the function term alone, despite the pairs being non-homologous, unevenly distributed across taxa, and of direct interest as drug targets; family-level grounding (PANTHER, InterPro) is the only route to that distinction. Term status (updated 2026-10-06). QuickGO now reports the whole family of glycolysis route terms as obsolete with GO:0006096 (now labelled "glycolysis") as the target: GO:0061615 (this module's core term), GO:0061616, GO:0061619, GO:0061621, GO:0061622, GO:0061625 and GO:0061633. GOA has already migrated the corresponding annotations (the S. pombe glycolysis gene reviews MODIFY them to GO:0006096). The ontology release pinned for validation in this repository still has these terms live, so the concept ids are kept for now; when the pinned GO is updated, the module core concept should become GO:0006096 and the entry-route variants should keep their preferred_term without a GO id. GO no longer distinguishes the EMP route from other glycolytic routes by a process term, so the EMP-versus-Entner-Doudoroff distinction will rest on the part structure of this module rather than on its concept. The PomBase model title "canonical glycolysis (GO:0061621)" is quoted as the model's own title. Before leaving DRAFT. This template has not been checked for satisfiability against a bacterial or archaeal genome. The archaeal ADP-dependent kinase and ferredoxin-dependent oxidation variants in particular are asserted from the GO term inventory and general pathway knowledge rather than from a specific annotated genome, and should be confirmed against one.

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