title: Hypothesis: butyrate is not an HDAC inhibitor, but a product inhibitor of deacetylation.
abstract: The short-chain fatty acid butyrate is classically referred to as an inhibitor of histone deacetylases (HDACi), however evidence from direct assays is both sparse and contradictory. This paper assesses the strength of the historical evidence, potential gaps, inadequacies and simplifications in the butyrate-as-HDACi hypothesis. An alternate model to explain the action of butyrate is proposed wherein butyrate acts as a product inhibitor of deacetylation. The model makes testable predictions which may enable future determination of the mode of action of this and other SCFAs.
authors.affiliation: Academic Unit of Surgical Oncology, Department of Oncology, University of Sheffield, Sheffield, UK. b.m.corfe@sheffield.ac.uk
authors.forename: Bernard M
authors.initials: BM
authors.lastname: Corfe
mesh_terms: D000107:Acetylation / Q000187:drug effects; D002087:Butyrates / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D053858:Metabolic Networks and Pathways; D008954:Models, Biological
chemical_list: D002087:Butyrates; D056572:Histone Deacetylase Inhibitors