{"id":"35c0de7f-89d3-5d0e-9e65-945c6d9417b1","stable_key":"d96b230c-481b-535b-930c-04eb87ec7f02:s-allylcysteine-upstream-kinase","predicate":"changes_tested","statement":"Pharmacological inhibitor experiments implicated CaMKK and SIRT1 in SAC-associated AMPK signaling.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"88f578ec-20dc-51ca-80aa-c18625695cfd","mechanism_event_label":"Upstream pathway perturbations identify dependencies to investigate.","subject":{"id":"8c2c295d-68b3-5e62-b1a7-00fcf915e3cc","slug":"s-allylcysteine","display_name":"S-allyl-L-cysteine / SAC","entity_type_key":"small_molecule"},"object":{"id":"30266915-654f-5093-822f-72d037f5178d","slug":"human-sac-camkk-sirt1-dependence","display_name":"CaMKK/SIRT1-sensitive SAC signaling in HepG2 cells","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"88f578ec-20dc-51ca-80aa-c18625695cfd","stable_key":"d96b230c-481b-535b-930c-04eb87ec7f02:s-allylcysteine-upstream-kinase-event","event_type":"observed_relationship","label":"Upstream pathway perturbations identify dependencies to investigate.","description":"Pharmacological inhibitor experiments implicated CaMKK and SIRT1 in SAC-associated AMPK signaling.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"8c2c295d-68b3-5e62-b1a7-00fcf915e3cc","slug":"s-allylcysteine","display_name":"S-allyl-L-cysteine / SAC","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"30266915-654f-5093-822f-72d037f5178d","slug":"human-sac-camkk-sirt1-dependence","display_name":"CaMKK/SIRT1-sensitive SAC signaling in HepG2 cells","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"b8e1bfa9-c412-5f35-97af-cfc722123d27","slug":"sirt1","display_name":"SIRT1","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"95bc303f-ad04-59ea-8e1e-32f9e8b72c56","slug":"human-ampk-complexes","display_name":"Human AMP-activated protein kinase complexes","entity_type_key":"protein_family"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"acting_entity","value_text":"s-allylcysteine","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"dose","value_text":"Not specified in accessed abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"duration","value_text":"Not specified in accessed abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_comparison","value_text":"SAC addition; pathway inhibitor comparisons","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Free-fatty-acid-treated HepG2 cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"interpretation_status","value_text":"Source-derived research curation; not independent primary verification","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Abstract does not specify CaMKK isoform, inhibitor selectivity or direct SIRT1 activation. No NAD or calcium depletion is demonstrated.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"S-allylcysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"s-allylcysteine","display_name":"S-allyl-L-cysteine / SAC","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Upstream pathway perturbations identify dependencies to investigate.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[23465592] S-allyl cysteine attenuates free fatty acid-induced lipogenesis in human HepG2 cells through activation of the AMP-activated protein kinase-dependent pathway. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23465592/ · DOI 10.1016/j.jnutbio.2012.12.006","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"Cell culture","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Free-fatty-acid-treated HepG2 cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"6b35a8e3-e676-55c7-a2e4-3b8e83b9605e","evidence_kind":"source_excerpt","locator":"Lines 212-219","start_line":212,"end_line":219,"excerpt":"## s-allylcysteine-upstream-kinase\nUpstream pathway perturbations identify dependencies to investigate.\nPharmacological inhibitor experiments implicated CaMKK and SIRT1 in SAC-associated AMPK signaling.\nModel: Free-fatty-acid-treated HepG2 cells\nLimitations: Abstract does not specify CaMKK isoform, inhibitor selectivity or direct SIRT1 activation. No NAD or calcium depletion is demonstrated.\nEvidence access: Primary abstract\n[23465592] S-allyl cysteine attenuates free fatty acid-induced lipogenesis in human HepG2 cells through activation of the AMP-activated protein kinase-dependent pathway. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23465592/ · DOI 10.1016/j.jnutbio.2012.12.006\nStructured context: {\"organism\": \"Homo sapiens\", \"tissue_or_cell_type\": \"Free-fatty-acid-treated HepG2 cells\", \"dose\": \"Not specified in accessed abstract\", \"duration\": \"Not specified in accessed abstract\", \"route\": \"Cell culture\", \"experimental_comparison\": \"SAC addition; pathway inhibitor comparisons\", \"acting_entity\": \"s-allylcysteine\", \"interpretation_status\": \"Source-derived research curation; not independent primary verification\"}","model_system":"Free-fatty-acid-treated HepG2 cells","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"3b0d58f9-8a69-579d-9920-518399a9a8bb","stable_key":"import-d96b230c-481b-535b-930c-04eb87ec7f02","title":"S-allylcysteine: sulfur signaling, redox responses and cross-nutrient mechanisms (2026-09-20)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"91d7aeac82e42ce559d13dd8a2e0165d37760f7f555dd01c80e0604fa6e71ea2","revision_id":"545e497c-e5e3-543c-b26b-b297cbc7bbec","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}