{ "schemaVersion": "BASE-biological-assertion/1.1.0", "caseStudy": { "slug": "cellular-respiration", "title": "Where Cellular Respiration Gets Its ATP" }, "context": { "scope": "Selected aerobic human-cell pathway route from glucose oxidation to oxidative phosphorylation", "organism": "Homo sapiens", "taxonId": "9606", "population": "Human curated pathway model; tissue, cell type, substrate supply, and energetic demand vary", "exposureContext": "Oxygen is available as the terminal electron acceptor in this selected aerobic route; pathway flux and ATP yield vary with cell state and coupling." }, "groups": [ { "id": "carbon", "title": "Carbon Through the Pathway", "description": "Track glucose carbon through pyruvate oxidation and the citric acid cycle.", "assertionIds": [ "respiration-glycolysis-carbon-and-carriers", "respiration-pyruvate-oxidation-links-to-tca", "respiration-tca-loads-electron-carriers" ] }, { "id": "electrons", "title": "Electrons, Oxygen & Proton Gradient", "description": "Follow reducing equivalents through the inner-membrane respiratory chain.", "assertionIds": [ "respiration-electron-chain-uses-oxygen", "respiration-electron-transfer-builds-proton-gradient" ] }, { "id": "atp", "title": "Chemiosmosis & ATP Yield", "description": "See how ATP synthase uses the gradient and why yield depends on context.", "assertionIds": [ "respiration-atp-synthase-couples-proton-flow", "respiration-atp-yield-is-context-dependent" ] } ], "assertions": [ { "id": "respiration-glycolysis-carbon-and-carriers", "version": 1, "subjectId": "pathway-glycolysis", "predicate": "CONVERTS", "objectId": "molecule-pyruvate", "statement": "In the canonical human glycolytic sequence, one glucose is converted to two pyruvate, with a net production of two ATP and two NADH per glucose.", "qualifier": "The ATP value is the net substrate-level yield for the pathway under the standard accounting convention. Glycolysis occurs in the cytosol and does not itself require oxygen; pyruvate and NADH have multiple possible fates.", "evidenceKind": "curated_pathway", "context": { "scope": "Selected aerobic human-cell pathway route from glucose oxidation to oxidative phosphorylation", "organism": "Homo sapiens", "taxonId": "9606", "population": "Human curated pathway model; tissue, cell type, substrate supply, and energetic demand vary", "exposureContext": "Oxygen is available as the terminal electron acceptor in this selected aerobic route; pathway flux and ATP yield vary with cell state and coupling." }, "references": [ { "referenceId": "reactome-glycolysis", "relation": "supports", "sourceRecordId": "Reactome:R-HSA-70171", "sourceVersion": "Stable identifier; release not recorded in this snapshot" }, { "referenceId": "mboc-glycolysis", "relation": "supports", "sourceRecordId": "NCBI Bookshelf:NBK26882", "sourceVersion": "Edition/version not recorded in this snapshot" } ] }, { "id": "respiration-pyruvate-oxidation-links-to-tca", "version": 1, "subjectId": "pathway-pyruvate-oxidation", "predicate": "CONVERTS", "objectId": "molecule-acetyl-coa", "statement": "In human mitochondria under aerobic metabolism, pyruvate oxidation produces acetyl-CoA, CO₂, and NADH, linking glycolysis to the citric acid cycle.", "qualifier": "This is the mitochondrial pyruvate dehydrogenase route; pyruvate can be reduced to lactate or enter other reactions depending on tissue and metabolic state.", "evidenceKind": "curated_pathway", "context": { "scope": "Selected aerobic human-cell pathway route from glucose oxidation to oxidative phosphorylation", "organism": "Homo sapiens", "taxonId": "9606", "population": "Human curated pathway model; tissue, cell type, substrate supply, and energetic demand vary", "exposureContext": "Oxygen is available as the terminal electron acceptor in this selected aerobic route; pathway flux and ATP yield vary with cell state and coupling." }, "references": [ { "referenceId": "reactome-pyruvate-oxidation", "relation": "supports", "sourceRecordId": "Reactome:R-HSA-70268", "sourceVersion": "Stable identifier; release not recorded in this snapshot" }, { "referenceId": "reactome-aerobic-respiration", "relation": "supports", "sourceRecordId": "Reactome:R-HSA-1428517", "sourceVersion": "Reviewed 2024-05-16; release not recorded in this snapshot" } ] }, { "id": "respiration-tca-loads-electron-carriers", "version": 1, "subjectId": "pathway-tca-cycle", "predicate": "GENERATES", "objectId": "molecule-nadh", "statement": "The citric acid cycle oxidizes acetyl-derived carbon and transfers reducing equivalents to NADH and FADH₂ while regenerating its starting acceptor.", "qualifier": "The cycle is amphibolic: intermediates also supply biosynthesis. The carbon atoms released as CO₂ in a given turn are not necessarily the same two atoms that entered as acetyl-CoA in that turn.", "evidenceKind": "curated_pathway", "context": { "scope": "Selected aerobic human-cell pathway route from glucose oxidation to oxidative phosphorylation", "organism": "Homo sapiens", "taxonId": "9606", "population": "Human curated pathway model; tissue, cell type, substrate supply, and energetic demand vary", "exposureContext": "Oxygen is available as the terminal electron acceptor in this selected aerobic route; pathway flux and ATP yield vary with cell state and coupling." }, "references": [ { "referenceId": "reactome-tca", "relation": "supports", "sourceRecordId": "Reactome:R-HSA-71403", "sourceVersion": "Stable identifier; release not recorded in this snapshot" }, { "referenceId": "reactome-aerobic-respiration", "relation": "supports", "sourceRecordId": "Reactome:R-HSA-1428517", "sourceVersion": "Reviewed 2024-05-16; release not recorded in this snapshot" } ] }, { "id": "respiration-electron-chain-uses-oxygen", "version": 1, "subjectId": "pathway-oxidative-phosphorylation", "predicate": "TRANSFERS_ELECTRONS_TO", "objectValue": "Oxygen, the terminal electron acceptor in this aerobic respiratory route; water is formed", "statement": "NADH and FADH₂ donate electrons to the respiratory chain; in aerobic mitochondria, oxygen accepts electrons at the end of the chain and is reduced to water.", "qualifier": "This statement describes aerobic respiration. Cells and organisms can use other electron acceptors or fermentation strategies under different biological conditions.", "evidenceKind": "curated_pathway", "context": { "scope": "Selected aerobic human-cell pathway route from glucose oxidation to oxidative phosphorylation", "organism": "Homo sapiens", "taxonId": "9606", "population": "Human curated pathway model; tissue, cell type, substrate supply, and energetic demand vary", "exposureContext": "Oxygen is available as the terminal electron acceptor in this selected aerobic route; pathway flux and ATP yield vary with cell state and coupling." }, "references": [ { "referenceId": "reactome-respiratory-electron-transport", "relation": "supports", "sourceRecordId": "Reactome:R-HSA-611105", "sourceVersion": "Stable identifier; release not recorded in this snapshot" }, { "referenceId": "ncbi-electron-transport", "relation": "supports", "sourceRecordId": "NCBI Bookshelf:NBK26904", "sourceVersion": "Edition/version not recorded in this snapshot" } ] }, { "id": "respiration-electron-transfer-builds-proton-gradient", "version": 1, "subjectId": "pathway-oxidative-phosphorylation", "predicate": "BUILDS", "objectValue": "An electrochemical proton gradient across the inner mitochondrial membrane", "statement": "Electron-transfer energy is coupled to proton movement across the inner mitochondrial membrane, storing part of the energy as an electrochemical gradient.", "qualifier": "The gradient also powers other transport and cellular processes. Proton pumping and coupling vary among respiratory complexes, tissues, and mitochondrial states.", "evidenceKind": "curated_pathway", "context": { "scope": "Selected aerobic human-cell pathway route from glucose oxidation to oxidative phosphorylation", "organism": "Homo sapiens", "taxonId": "9606", "population": "Human curated pathway model; tissue, cell type, substrate supply, and energetic demand vary", "exposureContext": "Oxygen is available as the terminal electron acceptor in this selected aerobic route; pathway flux and ATP yield vary with cell state and coupling." }, "references": [ { "referenceId": "reactome-aerobic-respiration", "relation": "supports", "sourceRecordId": "Reactome:R-HSA-1428517", "sourceVersion": "Reviewed 2024-05-16; release not recorded in this snapshot" }, { "referenceId": "ncbi-electron-transport", "relation": "supports", "sourceRecordId": "NCBI Bookshelf:NBK26904", "sourceVersion": "Edition/version not recorded in this snapshot" } ] }, { "id": "respiration-atp-synthase-couples-proton-flow", "version": 1, "subjectId": "pathway-oxidative-phosphorylation", "predicate": "USES_PROTON_GRADIENT_TO_FORM", "objectId": "molecule-atp", "statement": "ATP synthase couples proton flow down the electrochemical gradient to ATP formation from ADP and inorganic phosphate.", "qualifier": "This is chemiosmotic coupling, not a direct transfer of an electron to ADP. ATP synthase can run in reverse under some conditions, and cellular ATP production depends on coupling and demand.", "evidenceKind": "curated_pathway", "context": { "scope": "Selected aerobic human-cell pathway route from glucose oxidation to oxidative phosphorylation", "organism": "Homo sapiens", "taxonId": "9606", "population": "Human curated pathway model; tissue, cell type, substrate supply, and energetic demand vary", "exposureContext": "Oxygen is available as the terminal electron acceptor in this selected aerobic route; pathway flux and ATP yield vary with cell state and coupling." }, "references": [ { "referenceId": "reactome-atp-synthase", "relation": "supports", "sourceRecordId": "Reactome:R-HSA-164835", "sourceVersion": "Stable identifier; release not recorded in this snapshot" }, { "referenceId": "mboc-oxidative-phosphorylation-mechanism", "relation": "supports", "sourceRecordId": "NCBI Bookshelf:NBK9885", "sourceVersion": "Edition/version not recorded in this snapshot" } ] }, { "id": "respiration-atp-yield-is-context-dependent", "version": 1, "subjectId": "concept-cellular-respiration", "predicate": "ATP_YIELD_DEPENDS_ON", "objectValue": "Substrate oxidation, shuttle systems, proton leak, coupling, tissue, and cell state", "statement": "A single universal ATP total for complete glucose oxidation is not a dependable biological constant; realized yield depends on transport, coupling, and cellular context.", "qualifier": "Textbook stoichiometric estimates are useful models, but they should be labeled with their assumptions and should not be presented as measured output in every cell.", "evidenceKind": "mechanistic_review", "context": { "scope": "Selected aerobic human-cell pathway route from glucose oxidation to oxidative phosphorylation", "organism": "Homo sapiens", "taxonId": "9606", "population": "Human curated pathway model; tissue, cell type, substrate supply, and energetic demand vary", "exposureContext": "Oxygen is available as the terminal electron acceptor in this selected aerobic route; pathway flux and ATP yield vary with cell state and coupling." }, "references": [ { "referenceId": "reactome-aerobic-respiration", "relation": "supports", "sourceRecordId": "Reactome:R-HSA-1428517", "sourceVersion": "Reviewed 2024-05-16; pathway includes uncoupling" }, { "referenceId": "mboc-oxidative-phosphorylation-mechanism", "relation": "qualifies", "sourceRecordId": "NCBI Bookshelf:NBK9885", "sourceVersion": "Edition/version not recorded in this snapshot" } ] } ], "limitation": "This is a selected aerobic human-cell route, not a complete metabolic network. Glycolysis can proceed without oxygen; pyruvate and TCA intermediates have other fates; ATP yield depends on coupling, transport, tissue, substrate, and cell state.", "release": { "snapshotSchemaVersion": "BASE-case-snapshot/1.0.0", "exportedAt": "2026-10-11T01:50:31.557Z", "caseContentRevision": 1, "diagramRevision": 1, "diagramId": "respiration-case-map", "sourceCommitSha": "e97dc5327f9d807ecaf44b77e87ddf6f3f6d2bc2", "snapshotSha256": "57f955dd4be767754a31dea91a42177ac8a5ff8475946e9b665c88c1b256618f" }, "snapshot": { "releaseInputs": { "caseContentRevision": 1, "diagramRevision": 1, "diagramId": "respiration-case-map", "sourceCommitSha": "e97dc5327f9d807ecaf44b77e87ddf6f3f6d2bc2" }, "caseStudy": { "slug": "cellular-respiration", "title": "Where Cellular Respiration Gets Its ATP", "area": "Metabolism · Matter and Energy", "question": "How does breaking down glucose help a cell make ATP?", "overview": "Cellular respiration transfers energy from fuel through a series of reactions. Carbon atoms from glucose are rearranged and released as carbon dioxide; electrons are transferred to carriers and ultimately help power ATP production.", "mechanism": [ "Glycolysis takes place in the cytosol. Per glucose, the canonical pathway makes two pyruvate, two NADH, and a net two ATP by substrate-level phosphorylation; glycolysis itself does not require oxygen.", "In aerobic human cells, pyruvate can enter mitochondria and be converted to acetyl-CoA, CO₂, and NADH. Pyruvate can also be reduced to lactate or enter other reactions depending on cell state.", "The citric acid cycle oxidizes acetyl-derived carbon in the mitochondrial matrix, generating NADH and FADH₂ and a small amount of nucleotide triphosphate directly. Its intermediates also feed biosynthesis.", "NADH and FADH₂ carry electrons to the respiratory chain in the inner mitochondrial membrane. Electron transfer to oxygen releases energy; oxygen is reduced to water at the end of the aerobic chain.", "Energy from electron transfer helps pump protons across the inner membrane. The resulting electrochemical gradient stores energy and can also support other mitochondrial transport processes.", "ATP synthase lets protons flow back down the gradient and couples that flow to ATP formation from ADP and phosphate. This is chemiosmotic coupling, not a direct transfer of electrons to ATP.", "Carbon atoms and electrons follow related but distinct paths: carbon leaves as CO₂, while electron carriers transfer reducing power to oxygen. Actual ATP yield varies with shuttles, coupling, tissue, substrate, and cell state." ], "evidence": "This page shows a selected aerobic human-cell route, not the complete metabolic network. Glycolysis can proceed without oxygen, pyruvate and TCA intermediates have other fates, and a single universal ATP yield hides assumptions about coupling, transport, tissue, and metabolic state.", "entityIds": [ "concept-cellular-respiration", "pathway-glycolysis", "pathway-pyruvate-oxidation", "pathway-tca-cycle", "pathway-oxidative-phosphorylation", "molecule-glucose", "molecule-pyruvate", "molecule-acetyl-coa", "molecule-nadh", "molecule-fadh2", "molecule-atp", "molecule-carbon-dioxide" ], "references": [ "hhmi-respiration", "openstax-carbon-cycle", "reactome-glycolysis", "mboc-glycolysis", "reactome-pyruvate-oxidation", "reactome-tca", "reactome-respiratory-electron-transport", "reactome-aerobic-respiration", "reactome-atp-synthase", "ncbi-electron-transport", "mboc-oxidative-phosphorylation-mechanism" ], "assertionIds": [ "respiration-glycolysis-carbon-and-carriers", "respiration-pyruvate-oxidation-links-to-tca", "respiration-tca-loads-electron-carriers", "respiration-electron-chain-uses-oxygen", "respiration-electron-transfer-builds-proton-gradient", "respiration-atp-synthase-couples-proton-flow", "respiration-atp-yield-is-context-dependent" ], "check": [ { "question": "What role does oxygen play in aerobic cellular respiration?", "answer": "Oxygen accepts electrons at the end of the respiratory electron transport chain, allowing electron flow to continue." }, { "question": "Does glycolysis make most of the ATP from aerobic glucose oxidation?", "answer": "No. Glycolysis makes a small amount directly; most ATP is generated through oxidative phosphorylation." }, { "question": "Why do the carbon and electron arrows need to be shown separately?", "answer": "Glucose carbon is eventually released as CO₂, while electrons are carried by NADH and FADH₂ to the respiratory chain and ultimately transferred to oxygen. Matter flow and energy transfer are connected but not identical." }, { "question": "How does the proton gradient help make ATP?", "answer": "Electron transfer builds an electrochemical gradient across the inner mitochondrial membrane. Proton flow through ATP synthase is coupled to ATP formation from ADP and phosphate." }, { "question": "Why should an ATP-per-glucose number include assumptions?", "answer": "The realized yield depends on cytosolic NADH shuttles, proton leak, coupling efficiency, transport costs, tissue, substrate use, and cell state." } ] }, "diagram": { "revision": 1, "id": "respiration-case-map", "title": "Carbon exits; electrons power ATP production", "subtitle": "Cellular respiration is a linked set of pathways in different locations, with ATP made along the way.", "note": "This map shows a simplified aerobic route in a eukaryotic cell. Glycolysis and the citric acid cycle make some ATP-equivalent directly; most ATP from complete glucose oxidation is associated with oxidative phosphorylation. Oxygen is the terminal electron acceptor in the respiratory chain and is reduced to water.", "sources": [ { "label": "HHMI BioInteractive · Cellular Respiration Hub", "href": "https://www.biointeractive.org/classroom-resources/cellular-respiration-hub" }, { "label": "NCBI Bookshelf · Electron-Transport Chains", "href": "https://www.ncbi.nlm.nih.gov/books/NBK26904/" } ], "lanes": [ { "label": "Glycolysis", "note": "The canonical human sequence converts glucose to pyruvate and yields ATP and NADH.", "links": [ "converts glucose carbon to" ], "assertionIds": [ "respiration-glycolysis-carbon-and-carriers" ], "nodes": [ { "label": "Glycolysis", "detail": "One glucose is converted into two pyruvate, with net ATP and NADH production.", "href": "/pathway/glycolysis", "location": "Cytosol" }, { "label": "Pyruvate", "detail": "The three-carbon product can enter mitochondrial oxidation in aerobic cells or take other fates depending on context.", "href": "/molecule/pyruvate", "location": "Cytosol" } ] }, { "label": "Link to the citric acid cycle", "note": "Pyruvate oxidation connects glycolytic carbon to mitochondrial acetyl-CoA.", "links": [ "produces" ], "assertionIds": [ "respiration-pyruvate-oxidation-links-to-tca" ], "nodes": [ { "label": "Pyruvate oxidation", "detail": "In human mitochondria under aerobic metabolism, this step produces acetyl-CoA, CO₂, and NADH.", "href": "/pathway/pyruvate-oxidation", "location": "Mitochondrial matrix" }, { "label": "Acetyl-CoA", "detail": "The acetyl group can enter the citric acid cycle; other fates also exist.", "href": "/molecule/acetyl-coa", "location": "Mitochondrial matrix" } ] }, { "label": "Electron carriers", "note": "The citric acid cycle transfers reducing equivalents to multiple carriers.", "links": [ "generates" ], "assertionIds": [ "respiration-tca-loads-electron-carriers" ], "nodes": [ { "label": "Citric acid cycle", "detail": "The cycle oxidizes acetyl-derived carbon and regenerates its starting acceptor.", "href": "/pathway/tca-cycle", "location": "Mitochondrial matrix" }, { "label": "NADH + FADH₂", "detail": "Reduced carriers deliver electrons to the respiratory chain.", "href": "/molecule/nadh", "location": "Carrier pool" } ] }, { "label": "Oxygen as terminal electron acceptor", "note": "This assertion describes the aerobic mitochondrial route.", "links": [ "transfers electrons to" ], "assertionIds": [ "respiration-electron-chain-uses-oxygen" ], "nodes": [ { "label": "Oxidative phosphorylation", "detail": "NADH and FADH₂ donate electrons into the respiratory chain.", "href": "/pathway/oxidative-phosphorylation", "location": "Inner mitochondrial membrane" }, { "label": "Oxygen → water", "detail": "Oxygen accepts electrons at the end of this aerobic route and is reduced to water.", "href": "/molecule/water" } ] }, { "label": "Proton gradient", "note": "Electron transfer is coupled to proton movement across the inner membrane.", "links": [ "builds" ], "assertionIds": [ "respiration-electron-transfer-builds-proton-gradient" ], "nodes": [ { "label": "Respiratory electron transfer", "detail": "The chain couples electron-transfer energy to proton movement.", "href": "/pathway/oxidative-phosphorylation" }, { "label": "Electrochemical proton gradient", "detail": "The gradient stores part of the transferred energy across the inner mitochondrial membrane.", "href": "/concept/proton-motive-force" } ] }, { "label": "ATP synthesis", "note": "Chemiosmosis couples proton flow to ATP formation; actual ATP yield varies by context.", "links": [ "uses proton flow to form" ], "assertionIds": [ "respiration-atp-synthase-couples-proton-flow" ], "nodes": [ { "label": "Proton gradient + ATP synthase", "detail": "Proton flow down the electrochemical gradient drives ATP synthesis from ADP and inorganic phosphate.", "href": "/pathway/oxidative-phosphorylation" }, { "label": "ATP", "detail": "ATP supports transport, biosynthesis, movement, and other cell work.", "href": "/molecule/atp" } ] } ] }, "connectedRecords": [ { "id": "concept-cellular-respiration", "type": "process", "slug": "cellular-respiration", "name": "Cellular Respiration", "canonicalName": "Cellular respiration", "summary": "How cells transfer energy from fuel molecules into ATP, often using oxygen in the final electron-accepting step." }, { "id": "pathway-glycolysis", "type": "pathway", "slug": "glycolysis", "name": "Glycolysis", "canonicalName": "Glycolysis (human)", "summary": "The ten-step cytosolic pathway that splits one glucose into two pyruvate, with a net gain of 2 ATP and 2 NADH." }, { "id": "pathway-pyruvate-oxidation", "type": "pathway", "slug": "pyruvate-oxidation", "name": "Pyruvate Oxidation", "canonicalName": "Pyruvate oxidation in human metabolism", "summary": "The pyruvate dehydrogenase complex links glycolysis to the citric acid cycle by converting pyruvate to acetyl-CoA. It releases carbon dioxide and captures electrons in NADH; its reaction is effectively irreversible in cells." }, { "id": "pathway-tca-cycle", "type": "pathway", "slug": "tca-cycle", "name": "Citric Acid cycle", "canonicalName": "Citric acid cycle in human metabolism", "summary": "The citric acid cycle oxidizes the acetyl group of acetyl-CoA to two carbon dioxide molecules while regenerating oxaloacetate. Each turn yields three NADH, one FADH2, and one GTP (or ATP), which feed biosynthesis and oxidative phosphorylation." }, { "id": "pathway-oxidative-phosphorylation", "type": "pathway", "slug": "oxidative-phosphorylation", "name": "Oxidative Phosphorylation", "canonicalName": "Oxidative phosphorylation in human metabolism", "summary": "The respiratory chain transfers electrons from NADH and FAD-linked sources to oxygen. Complexes I, III, and IV pump protons; ATP synthase uses the proton-motive force to make ATP from ADP and phosphate." }, { "id": "molecule-glucose", "type": "molecule", "slug": "glucose", "name": "Glucose", "canonicalName": "Glucose", "summary": "A six-carbon sugar and the starting fuel for glycolysis." }, { "id": "molecule-pyruvate", "type": "molecule", "slug": "pyruvate", "name": "Pyruvate", "canonicalName": "Pyruvate", "summary": "The three-carbon end product of glycolysis. It can be oxidized in mitochondria or reduced to lactate." }, { "id": "molecule-acetyl-coa", "type": "molecule", "slug": "acetyl-coa", "name": "Acetyl-CoA", "canonicalName": "Acetyl-CoA", "summary": "A two-carbon acetyl donor that connects carbohydrate, lipid, amino-acid, and energy metabolism." }, { "id": "molecule-nadh", "type": "molecule", "slug": "nadh", "name": "NADH", "canonicalName": "NADH", "summary": "Reduced nicotinamide adenine dinucleotide, which carries electrons away from glycolysis." }, { "id": "molecule-fadh2", "type": "molecule", "slug": "fadh2", "name": "FADH2", "canonicalName": "FADH2", "summary": "Reduced flavin adenine dinucleotide that carries electrons to the respiratory chain." }, { "id": "molecule-atp", "type": "molecule", "slug": "atp", "name": "ATP", "canonicalName": "ATP", "summary": "Adenosine triphosphate, the cell's main short-term energy carrier." }, { "id": "molecule-carbon-dioxide", "type": "molecule", "slug": "carbon-dioxide", "name": "Carbon Dioxide", "canonicalName": "Carbon dioxide", "summary": "A small carbon-containing molecule fixed into organic compounds by photosynthesis and released by many respiratory and decomposition processes." } ], "references": [ { "id": "hhmi-respiration", "title": "Cellular Respiration Hub", "publisher": "HHMI BioInteractive", "url": "https://www.biointeractive.org/classroom-resources/cellular-respiration-hub", "kind": "guide" }, { "id": "openstax-carbon-cycle", "title": "Biogeochemical Cycles", "publisher": "OpenStax Biology 2e", "url": "https://openstax.org/books/biology-2e/pages/46-3-biogeochemical-cycles", "kind": "textbook" }, { "id": "reactome-glycolysis", "title": "Glycolysis (R-HSA-70171)", "publisher": "Reactome · Homo sapiens", "url": "https://reactome.org/content/detail/R-HSA-70171", "kind": "pathway" }, { "id": "mboc-glycolysis", "title": "Molecular Biology of the Cell: glycolysis (NBK26882)", "publisher": "Alberts et al. · NCBI Bookshelf", "url": "https://www.ncbi.nlm.nih.gov/books/NBK26882/", "kind": "textbook" }, { "id": "reactome-pyruvate-oxidation", "title": "Pyruvate metabolism (R-HSA-70268)", "publisher": "Reactome · Homo sapiens", "url": "https://reactome.org/content/detail/R-HSA-70268", "kind": "pathway" }, { "id": "reactome-tca", "title": "Citric acid cycle (R-HSA-71403)", "publisher": "Reactome · Homo sapiens", "url": "https://reactome.org/content/detail/R-HSA-71403", "kind": "pathway" }, { "id": "reactome-respiratory-electron-transport", "title": "Respiratory electron transport (R-HSA-611105)", "publisher": "Reactome · Homo sapiens", "url": "https://reactome.org/content/detail/R-HSA-611105", "kind": "pathway" }, { "id": "reactome-aerobic-respiration", "title": "Aerobic respiration and respiratory electron transport (R-HSA-1428517)", "publisher": "Reactome · Homo sapiens", "url": "https://reactome.org/content/detail/R-HSA-1428517", "kind": "pathway" }, { "id": "reactome-atp-synthase", "title": "ATP synthase (R-HSA-164835)", "publisher": "Reactome · Homo sapiens", "url": "https://www.reactome.org/content/detail/R-HSA-164835", "kind": "pathway" }, { "id": "ncbi-electron-transport", "title": "Electron-Transport Chains", "publisher": "Molecular Biology of the Cell · NCBI Bookshelf", "url": "https://www.ncbi.nlm.nih.gov/books/NBK26904/", "kind": "textbook" }, { "id": "mboc-oxidative-phosphorylation-mechanism", "title": "The Mechanism of Oxidative Phosphorylation", "publisher": "The Cell · NCBI Bookshelf", "url": "https://www.ncbi.nlm.nih.gov/books/NBK9885/", "kind": "textbook" } ], "mechanismEvidence": { "schemaVersion": "BASE-biological-assertion/1.1.0", "context": { "scope": "Selected aerobic human-cell pathway route from glucose oxidation to oxidative phosphorylation", "organism": "Homo sapiens", "taxonId": "9606", "population": "Human curated pathway model; tissue, cell type, substrate supply, and energetic demand vary", "exposureContext": "Oxygen is available as the terminal electron acceptor in this selected aerobic route; pathway flux and ATP yield vary with cell state and coupling." }, "groups": [ { "id": "carbon", "title": "Carbon Through the Pathway", "description": "Track glucose carbon through pyruvate oxidation and the citric acid cycle.", "assertionIds": [ "respiration-glycolysis-carbon-and-carriers", "respiration-pyruvate-oxidation-links-to-tca", "respiration-tca-loads-electron-carriers" ] }, { "id": "electrons", "title": "Electrons, Oxygen & Proton Gradient", "description": "Follow reducing equivalents through the inner-membrane respiratory chain.", "assertionIds": [ "respiration-electron-chain-uses-oxygen", "respiration-electron-transfer-builds-proton-gradient" ] }, { "id": "atp", "title": "Chemiosmosis & ATP Yield", "description": "See how ATP synthase uses the gradient and why yield depends on context.", "assertionIds": [ "respiration-atp-synthase-couples-proton-flow", "respiration-atp-yield-is-context-dependent" ] } ], "assertions": [ { "id": "respiration-glycolysis-carbon-and-carriers", "version": 1, "subjectId": "pathway-glycolysis", "predicate": "CONVERTS", "objectId": "molecule-pyruvate", "statement": "In the canonical human glycolytic sequence, one glucose is converted to two pyruvate, with a net production of two ATP and two NADH per glucose.", "qualifier": "The ATP value is the net substrate-level yield for the pathway under the standard accounting convention. Glycolysis occurs in the cytosol and does not itself require oxygen; pyruvate and NADH have multiple possible fates.", "evidenceKind": "curated_pathway", "context": { "scope": "Selected aerobic human-cell pathway route from glucose oxidation to oxidative phosphorylation", "organism": "Homo sapiens", "taxonId": "9606", "population": "Human curated pathway model; tissue, cell type, substrate supply, and energetic demand vary", "exposureContext": "Oxygen is available as the terminal electron acceptor in this selected aerobic route; pathway flux and ATP yield vary with cell state and coupling." }, "references": [ { "referenceId": "reactome-glycolysis", "relation": "supports", "sourceRecordId": "Reactome:R-HSA-70171", "sourceVersion": "Stable identifier; release not recorded in this snapshot" }, { "referenceId": "mboc-glycolysis", "relation": "supports", "sourceRecordId": "NCBI Bookshelf:NBK26882", "sourceVersion": "Edition/version not recorded in this snapshot" } ] }, { "id": "respiration-pyruvate-oxidation-links-to-tca", "version": 1, "subjectId": "pathway-pyruvate-oxidation", "predicate": "CONVERTS", "objectId": "molecule-acetyl-coa", "statement": "In human mitochondria under aerobic metabolism, pyruvate oxidation produces acetyl-CoA, CO₂, and NADH, linking glycolysis to the citric acid cycle.", "qualifier": "This is the mitochondrial pyruvate dehydrogenase route; pyruvate can be reduced to lactate or enter other reactions depending on tissue and metabolic state.", "evidenceKind": "curated_pathway", "context": { "scope": "Selected aerobic human-cell pathway route from glucose oxidation to oxidative phosphorylation", "organism": "Homo sapiens", "taxonId": "9606", "population": "Human curated pathway model; tissue, cell type, substrate supply, and energetic demand vary", "exposureContext": "Oxygen is available as the terminal electron acceptor in this selected aerobic route; pathway flux and ATP yield vary with cell state and coupling." }, "references": [ { "referenceId": "reactome-pyruvate-oxidation", "relation": "supports", "sourceRecordId": "Reactome:R-HSA-70268", "sourceVersion": "Stable identifier; release not recorded in this snapshot" }, { "referenceId": "reactome-aerobic-respiration", "relation": "supports", "sourceRecordId": "Reactome:R-HSA-1428517", "sourceVersion": "Reviewed 2024-05-16; release not recorded in this snapshot" } ] }, { "id": "respiration-tca-loads-electron-carriers", "version": 1, "subjectId": "pathway-tca-cycle", "predicate": "GENERATES", "objectId": "molecule-nadh", "statement": "The citric acid cycle oxidizes acetyl-derived carbon and transfers reducing equivalents to NADH and FADH₂ while regenerating its starting acceptor.", "qualifier": "The cycle is amphibolic: intermediates also supply biosynthesis. The carbon atoms released as CO₂ in a given turn are not necessarily the same two atoms that entered as acetyl-CoA in that turn.", "evidenceKind": "curated_pathway", "context": { "scope": "Selected aerobic human-cell pathway route from glucose oxidation to oxidative phosphorylation", "organism": "Homo sapiens", "taxonId": "9606", "population": "Human curated pathway model; tissue, cell type, substrate supply, and energetic demand vary", "exposureContext": "Oxygen is available as the terminal electron acceptor in this selected aerobic route; pathway flux and ATP yield vary with cell state and coupling." }, "references": [ { "referenceId": "reactome-tca", "relation": "supports", "sourceRecordId": "Reactome:R-HSA-71403", "sourceVersion": "Stable identifier; release not recorded in this snapshot" }, { "referenceId": "reactome-aerobic-respiration", "relation": "supports", "sourceRecordId": "Reactome:R-HSA-1428517", "sourceVersion": "Reviewed 2024-05-16; release not recorded in this snapshot" } ] }, { "id": "respiration-electron-chain-uses-oxygen", "version": 1, "subjectId": "pathway-oxidative-phosphorylation", "predicate": "TRANSFERS_ELECTRONS_TO", "objectValue": "Oxygen, the terminal electron acceptor in this aerobic respiratory route; water is formed", "statement": "NADH and FADH₂ donate electrons to the respiratory chain; in aerobic mitochondria, oxygen accepts electrons at the end of the chain and is reduced to water.", "qualifier": "This statement describes aerobic respiration. Cells and organisms can use other electron acceptors or fermentation strategies under different biological conditions.", "evidenceKind": "curated_pathway", "context": { "scope": "Selected aerobic human-cell pathway route from glucose oxidation to oxidative phosphorylation", "organism": "Homo sapiens", "taxonId": "9606", "population": "Human curated pathway model; tissue, cell type, substrate supply, and energetic demand vary", "exposureContext": "Oxygen is available as the terminal electron acceptor in this selected aerobic route; pathway flux and ATP yield vary with cell state and coupling." }, "references": [ { "referenceId": "reactome-respiratory-electron-transport", "relation": "supports", "sourceRecordId": "Reactome:R-HSA-611105", "sourceVersion": "Stable identifier; release not recorded in this snapshot" }, { "referenceId": "ncbi-electron-transport", "relation": "supports", "sourceRecordId": "NCBI Bookshelf:NBK26904", "sourceVersion": "Edition/version not recorded in this snapshot" } ] }, { "id": "respiration-electron-transfer-builds-proton-gradient", "version": 1, "subjectId": "pathway-oxidative-phosphorylation", "predicate": "BUILDS", "objectValue": "An electrochemical proton gradient across the inner mitochondrial membrane", "statement": "Electron-transfer energy is coupled to proton movement across the inner mitochondrial membrane, storing part of the energy as an electrochemical gradient.", "qualifier": "The gradient also powers other transport and cellular processes. Proton pumping and coupling vary among respiratory complexes, tissues, and mitochondrial states.", "evidenceKind": "curated_pathway", "context": { "scope": "Selected aerobic human-cell pathway route from glucose oxidation to oxidative phosphorylation", "organism": "Homo sapiens", "taxonId": "9606", "population": "Human curated pathway model; tissue, cell type, substrate supply, and energetic demand vary", "exposureContext": "Oxygen is available as the terminal electron acceptor in this selected aerobic route; pathway flux and ATP yield vary with cell state and coupling." }, "references": [ { "referenceId": "reactome-aerobic-respiration", "relation": "supports", "sourceRecordId": "Reactome:R-HSA-1428517", "sourceVersion": "Reviewed 2024-05-16; release not recorded in this snapshot" }, { "referenceId": "ncbi-electron-transport", "relation": "supports", "sourceRecordId": "NCBI Bookshelf:NBK26904", "sourceVersion": "Edition/version not recorded in this snapshot" } ] }, { "id": "respiration-atp-synthase-couples-proton-flow", "version": 1, "subjectId": "pathway-oxidative-phosphorylation", "predicate": "USES_PROTON_GRADIENT_TO_FORM", "objectId": "molecule-atp", "statement": "ATP synthase couples proton flow down the electrochemical gradient to ATP formation from ADP and inorganic phosphate.", "qualifier": "This is chemiosmotic coupling, not a direct transfer of an electron to ADP. ATP synthase can run in reverse under some conditions, and cellular ATP production depends on coupling and demand.", "evidenceKind": "curated_pathway", "context": { "scope": "Selected aerobic human-cell pathway route from glucose oxidation to oxidative phosphorylation", "organism": "Homo sapiens", "taxonId": "9606", "population": "Human curated pathway model; tissue, cell type, substrate supply, and energetic demand vary", "exposureContext": "Oxygen is available as the terminal electron acceptor in this selected aerobic route; pathway flux and ATP yield vary with cell state and coupling." }, "references": [ { "referenceId": "reactome-atp-synthase", "relation": "supports", "sourceRecordId": "Reactome:R-HSA-164835", "sourceVersion": "Stable identifier; release not recorded in this snapshot" }, { "referenceId": "mboc-oxidative-phosphorylation-mechanism", "relation": "supports", "sourceRecordId": "NCBI Bookshelf:NBK9885", "sourceVersion": "Edition/version not recorded in this snapshot" } ] }, { "id": "respiration-atp-yield-is-context-dependent", "version": 1, "subjectId": "concept-cellular-respiration", "predicate": "ATP_YIELD_DEPENDS_ON", "objectValue": "Substrate oxidation, shuttle systems, proton leak, coupling, tissue, and cell state", "statement": "A single universal ATP total for complete glucose oxidation is not a dependable biological constant; realized yield depends on transport, coupling, and cellular context.", "qualifier": "Textbook stoichiometric estimates are useful models, but they should be labeled with their assumptions and should not be presented as measured output in every cell.", "evidenceKind": "mechanistic_review", "context": { "scope": "Selected aerobic human-cell pathway route from glucose oxidation to oxidative phosphorylation", "organism": "Homo sapiens", "taxonId": "9606", "population": "Human curated pathway model; tissue, cell type, substrate supply, and energetic demand vary", "exposureContext": "Oxygen is available as the terminal electron acceptor in this selected aerobic route; pathway flux and ATP yield vary with cell state and coupling." }, "references": [ { "referenceId": "reactome-aerobic-respiration", "relation": "supports", "sourceRecordId": "Reactome:R-HSA-1428517", "sourceVersion": "Reviewed 2024-05-16; pathway includes uncoupling" }, { "referenceId": "mboc-oxidative-phosphorylation-mechanism", "relation": "qualifies", "sourceRecordId": "NCBI Bookshelf:NBK9885", "sourceVersion": "Edition/version not recorded in this snapshot" } ] } ], "limitation": "This is a selected aerobic human-cell route, not a complete metabolic network. Glycolysis can proceed without oxygen; pyruvate and TCA intermediates have other fates; ATP yield depends on coupling, transport, tissue, substrate, and cell state." } } }