Generic Embden-Meyerhof-Parnas (EMP) glycolysis module

Scope: direct entry at fructose 6-phosphate is in scope but not yet modelled. Two common routes land on fructose 6-phosphate rather than glucose 6-phosphate — fructose phosphorylated at C6 by a broad-specificity hexokinase, and mannose entering as mannose 6-phosphate and isomerised on by mannose-6-phosphate isomerase — and both are unambiguously INSIDE GO:0061615, since they pass through the defining intermediate. They are simply not represented by any current variant: every variant below produces glucose 6-phosphate, and the broad-specificity hexokinase annoton declares glucose as its substrate for clarity rather than because the enzyme is glucose-specific. A future revision should add a fructose/mannose entry variant; until then this is a known gap, not a scoping decision, and it is distinct from the exclusion described next. 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: participants use ANY_WITH_FUNCTION selectors throughout and terminal nodes intentionally do not name representative proteins, matching the sibling generic gluconeogenesis template. Leaf-grounding QC gaps on this file are therefore expected rather than defects. Concrete grounding to families, isozymes, and UniProt accessions lives in the instantiating modules (glycolysis_investment_phase, glycolysis_payoff_phase for human; entner_doudoroff_and_gluconeogenesis for the bacterial contrast case). 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. 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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