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<small>D</small>-β-Hydroxybutyric acid, along with [[butyric acid]], are the two primary [[endogenous]] [[agonist]]s of [[hydroxycarboxylic acid receptor 2]] (HCA<sub>2</sub>), a {{nowrap|[[Gi alpha subunit|G<sub>i/o</sub>-coupled]]}} [[GPCR]].<ref name="IUPHAR's comprehensive 2011 review on HCARs"/><ref name="IUPHAR-DB HCAR family page"/><ref name="β-D-hydroxybutyric acid IUPHAR">{{cite web|title=β-D-hydroxybutyric acid: Biological activity|url=http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=biology&ligandId=1593|website=IUPHAR/BPS Guide to Pharmacology|publisher=International Union of Basic and Clinical Pharmacology|access-date=5 February 2018}}</ref> |
<small>D</small>-β-Hydroxybutyric acid, along with [[butyric acid]], are the two primary [[endogenous]] [[agonist]]s of [[hydroxycarboxylic acid receptor 2]] (HCA<sub>2</sub>), a {{nowrap|[[Gi alpha subunit|G<sub>i/o</sub>-coupled]]}} [[GPCR]].<ref name="IUPHAR's comprehensive 2011 review on HCARs"/><ref name="IUPHAR-DB HCAR family page"/><ref name="β-D-hydroxybutyric acid IUPHAR">{{cite web|title=β-D-hydroxybutyric acid: Biological activity|url=http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=biology&ligandId=1593|website=IUPHAR/BPS Guide to Pharmacology|publisher=International Union of Basic and Clinical Pharmacology|access-date=5 February 2018}}</ref> |
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β-Hydroxybutyric acid is able to cross the [[blood-brain-barrier]] into the [[central nervous system]].<ref name="pmid27253067">{{cite journal | vauthors = Sleiman SF, Henry J, Al-Haddad R, El Hayek L, Abou Haidar E, Stringer T, Ulja D, Karuppagounder SS, Holson EB, Ratan RR, Ninan I, Chao MV | display-authors = 6 | title = Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate | journal = eLife | volume = 5 | date = June 2016 | pmid = 27253067 | pmc = 4915811 | doi = 10.7554/eLife.15092 |
β-Hydroxybutyric acid is able to cross the [[blood-brain-barrier]] into the [[central nervous system]].<ref name="pmid27253067">{{cite journal | vauthors = Sleiman SF, Henry J, Al-Haddad R, El Hayek L, Abou Haidar E, Stringer T, Ulja D, Karuppagounder SS, Holson EB, Ratan RR, Ninan I, Chao MV | display-authors = 6 | title = Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate | journal = eLife | volume = 5 | date = June 2016 | pmid = 27253067 | pmc = 4915811 | doi = 10.7554/eLife.15092 }}</ref> Levels of β-hydroxybutyric acid increase in the [[liver]], [[heart]], [[muscle]], [[brain]], and other tissues with [[exercise]], [[calorie restriction]], [[fasting]], and [[ketogenic diet]]s.<ref name="pmid27253067" /> The compound has been found to act as a [[histone deacetylase inhibitor|histone deacetylase (HDAC) inhibitor]].<ref name="pmid27253067" /> Through inhibition of the HDAC class I [[isoenzyme]]s [[HDAC2]] and [[HDAC3]], β-hydroxybutyric acid has been found to increase [[brain-derived neurotrophic factor]] (BDNF) levels and [[TrkB]] [[cell signaling|signaling]] in the [[hippocampus]].<ref name="pmid27253067" /> Moreover, a rodent study found that prolonged exercise increases plasma β-hydroxybutyrate concentrations, which induces [[promoter (genetics)|promoters]] of the BDNF gene in the hippocampus.<ref name="pmid27253067" /> These findings may have clinical relevance in the treatment of [[depression (mood)|depression]], [[anxiety]], and [[cognitive impairment]].<ref name="pmid27253067"/> |
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In [[epilepsy]] patients on the ketogenic diet, blood β-hydroxybutyrate levels correlate best with degree of [[seizure]] control. The threshold for optimal [[anticonvulsant]] effect appears to be approximately 4 mmol/L.<ref name="pmid11198492">{{cite journal | vauthors = Gilbert DL, Pyzik PL, Freeman JM | title = The ketogenic diet: seizure control correlates better with serum beta-hydroxybutyrate than with urine ketones | journal = Journal of Child Neurology | volume = 15 | issue = 12 | pages = 787–790 | date = December 2000 | pmid = 11198492 | doi = 10.1177/088307380001501203 | s2cid = 46659339 }}</ref> |
In [[epilepsy]] patients on the ketogenic diet, blood β-hydroxybutyrate levels correlate best with degree of [[seizure]] control. The threshold for optimal [[anticonvulsant]] effect appears to be approximately 4 mmol/L.<ref name="pmid11198492">{{cite journal | vauthors = Gilbert DL, Pyzik PL, Freeman JM | title = The ketogenic diet: seizure control correlates better with serum beta-hydroxybutyrate than with urine ketones | journal = Journal of Child Neurology | volume = 15 | issue = 12 | pages = 787–790 | date = December 2000 | pmid = 11198492 | doi = 10.1177/088307380001501203 | s2cid = 46659339 }}</ref> |
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