+ Human enzyme and GPCR binding Inhibited enzyme IC50 () Entry note HDAC1 16,000 HDAC2 12,000 HDAC3 9,000 HDAC4 2,000,000 Lower bound HDAC5 2,000,000 Lower bound HDAC6 2,000,000 Lower bound HDAC7 2,000,000 Lower bound HDAC8 15,000 HDAC9 2,000,000 Lower bound CA1 511,000 CA2 1,032,000 GPCR target pEC50 Entry note FFAR2 2.9–4.6 Full agonist FFAR3 3.8–4.9 Full agonist HCA2 2.8 Agonist Pharmacodynamics<unk>  (pKa 4.82) is fully ionized at physiological pH, so its anion is the material that is mainly relevant in biological systems. It is one of two primary endogenous agonists of human hydroxycarboxylic acid receptor 2 (HCA2, aka GPR109A), a G protein-coupled receptor (GPCR), Like other short-chain fatty acids (SCFAs), butyrate is an agonist at the free fatty acid receptors FFAR2 and FFAR3, which function as nutrient sensors that facilitate the homeostatic control of energy<unk> lance; however, among the group of SCFAs, only butyrate is an agonist of HCA2. It is also an HDAC inhibitor (specifically, HDAC1, HDAC2, HDAC3, and HDAC8), a drug that inhibits the function of histone deacetylase enzymes, thereby favoring an acetylated state of histones in cells. Histone acetylation loosens the structure of chromatin by reducing the electrostatic attraction between histones and DNA. In general, it is thought that transcription factors will be unable to access regions where histones are tightly associated with DNA (i.e., non-acetylated, e.g., heterochromatin). Therefore,<unk>  is thought to enhance the transcriptional activity at promoters, which are typically silenced or downregulated due to histone deacetylase activity. Pharmacokinetics Butyrate that is produced in the colon through microbial fermentation of dietary fiber is primarily absorbed and metabolized by colonocytes and the liver for the generation of ATP during energy metabolism; however, some butyrate is absorbed in the distal colon, which is not connected to the portal vein, thereby allowing for the systemic distribution of butyrate to multiple organ systems through the circulatory system. Butyrate that has reached systemic circulation can readily cross the blood-brain<unk> rrier via monocarboxylate transporters (i.e., certain members of the SLC16A group of transporters). Other transporters that mediate the passage of butyrate across lipid membranes include SLC5A8 (SMCT1), SLC27A1 (FATP1), and SLC27A4 (FATP4). Metabolism<unk>  is metabolized by various human XM-ligases (ACSM1, ACSM2B, ASCM3, ACSM4, ACSM5, and ACSM6), also known as butyrate–CoA ligase. The metabolite produced by this reaction is butyryl–CoA, and is produced as follows: :Adenosine triphosphate +<unk>  + coenzyme A → adenosine monophosphate + pyrophosphate + butyryl-CoA As a short-chain fatty acid, butyrate is metabolized by mitochondria as an energy (i.e., adenosine triphosphate or ATP) source through fatty acid metabolism. In particular, it is an important energy source for cells lining the mammalian colon (colonocytes). Without butyrates, colon cells undergo autophagy (i.e., self-digestion) and die. In humans, the butyrate precursor tributyrin, which is naturally present in butter, is metabolized by triacylglycerol lipase into dibutyrin and butyrate through the reaction: :Tributyrin + H2O → dibutyrin +<unk>
Butyric acid
Choline
Phenylacetic acid
Inositol
Gamma-Amino-beta-hydroxybutyric acid
Gluten
Palate
Keto acid