{"id":"9610e51f-2a35-5169-8c0a-1cec9af84203","stable_key":"08ce9896-9d1c-5bbf-b705-5bfe771091d5:b7-pc-reaction","predicate":"carboxylates","statement":"Human PC catalyzes two-step pyruvate carboxylation to oxaloacetate.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"22efc451-e111-566a-ac12-b1977141c622","mechanism_event_label":"PC replenishes a key carbon molecule used by several metabolic pathways.","subject":{"id":"b84a1471-7246-543a-8f35-2bedbca6bf0b","slug":"pc","display_name":"Human pyruvate carboxylase / PC","entity_type_key":"protein"},"object":{"id":"91e6d4f5-fba1-542d-b68a-57cc28e1e425","slug":"pyruvate","display_name":"Pyruvate","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"22efc451-e111-566a-ac12-b1977141c622","stable_key":"08ce9896-9d1c-5bbf-b705-5bfe771091d5:b7-pc-reaction-event","event_type":"biochemical_relationship","label":"PC replenishes a key carbon molecule used by several metabolic pathways.","description":"Human PC catalyzes two-step pyruvate carboxylation to oxaloacetate.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"37a8e96b-f95b-5ba7-a0bc-8ed3cfaf5fd8","slug":"biotin","display_name":"Biotin","entity_type_key":"small_molecule"},"role":"tethered cofactor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"edf44f6b-7b23-5b97-a86b-c940e5812b06","slug":"bicarbonate-ion","display_name":"Bicarbonate ion","entity_type_key":"ion"},"role":"carboxyl donor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"58b974f1-d389-5bf6-81cd-889c44442c42","slug":"atp","display_name":"ATP","entity_type_key":"small_molecule"},"role":"energy substrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"32119d9f-54be-5e6d-98da-1621b0e2421d","slug":"oxaloacetate","display_name":"Oxaloacetate","entity_type_key":"small_molecule"},"role":"product","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"b84a1471-7246-543a-8f35-2bedbca6bf0b","slug":"pc","display_name":"Human pyruvate carboxylase / PC","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"91e6d4f5-fba1-542d-b68a-57cc28e1e425","slug":"pyruvate","display_name":"Pyruvate","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/biotin-research/36283412.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"2a5fb8ec1c27e243b8c8ba158f2c58ab1592d9895eecf16438175b2a5778de15\", \"start_char\": 0, \"end_char\": 1060, \"text_sha256\": \"2a5fb8ec1c27e243b8c8ba158f2c58ab1592d9895eecf16438175b2a5778de15\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Time-resolved cryo-EM and biochemical analysis of human PC","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Pyruvate, ATP and acetyl-CoA catalytic conditions","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Purified-enzyme regulation is not evidence that consuming B5 or biotin stimulates this pathway in every tissue.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Biotin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"biotin","display_name":"Biotin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"PC replenishes a key carbon molecule used by several metabolic pathways.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[b7-p36283412] Mechanistic insight into allosteric activation of human pyruvate carboxylase by acetyl-CoA. (2022). https://pubmed.ncbi.nlm.nih.gov/36283412/ DOI: 10.1016/j.molcel.2022.09.033","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified human pyruvate carboxylase","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"6eb9223a-792b-5c18-a18a-7eb59b334dc4","evidence_kind":"source_excerpt","locator":"Lines 546-557","start_line":546,"end_line":557,"excerpt":"### b7-pc-reaction\nHuman PC catalyzes two-step pyruvate carboxylation to oxaloacetate.\nCondition category: normal\nnutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: PC replenishes a key carbon molecule used by several metabolic pathways.\norganism: Homo sapiens\ntissue_or_cell_type: Purified human pyruvate carboxylase\nexperimental_model: Time-resolved cryo-EM and biochemical analysis of human PC\nlimitations: Purified-enzyme regulation is not evidence that consuming B5 or biotin stimulates this pathway in every tissue.\nexposure: Pyruvate, ATP and acetyl-CoA catalytic conditions\nevidence_span: {\"source_cache\": \"artifacts/biotin-research/36283412.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"2a5fb8ec1c27e243b8c8ba158f2c58ab1592d9895eecf16438175b2a5778de15\", \"start_char\": 0, \"end_char\": 1060, \"text_sha256\": \"2a5fb8ec1c27e243b8c8ba158f2c58ab1592d9895eecf16438175b2a5778de15\"}\n[b7-p36283412] Mechanistic insight into allosteric activation of human pyruvate carboxylase by acetyl-CoA. 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