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{{cs1 config|name-list-style=vanc}} |
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{{DISPLAYTITLE:''beta''-Hydroxybutyric acid}} |
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{{Distinguish|β-Hydroxy β-methylbutyric acid}} |
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{{lowercase title}} |
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{{chembox |
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{{chembox |
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|Watchedfields = changed |
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| verifiedrevid = 407465551 |
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|verifiedrevid = 443420188 |
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| Name = ''beta''-Hydroxybutyric acid |
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| ImageFile = Beta-Hydroxybutyric acid-2D-skeletal.svg |
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|Name = β-Hydroxybutyric acid |
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|ImageFile = Beta-Hydroxybutyric acid-2D-skeletal.svg |
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| ImageSize = 200px |
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|ImageSize = 200px |
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|ImageClass = skin-invert |
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| IUPACName = 3-Hydroxybutanoic acid |
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|PIN = 3-Hydroxybutanoic acid |
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| OtherNames = |
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| Section1 = {{Chembox Identifiers |
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|Section1={{Chembox Identifiers |
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| InChI = 1/C4H8O3/c1-3(5)2-4(6)7/h3,5H,2H2,1H3,(H,6,7) |
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|InChI = 1/C4H8O3/c1-3(5)2-4(6)7/h3,5H,2H2,1H3,(H,6,7) |
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| InChIKey = WHBMMWSBFZVSSR-UHFFFAOYAO |
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|InChIKey = WHBMMWSBFZVSSR-UHFFFAOYAO |
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| SMILES1 = CC(CC(=O)O)O |
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|SMILES1 = CC(CC(=O)O)O |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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|ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 1162496 |
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|ChEMBL = 1162496 |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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|StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C4H8O3/c1-3(5)2-4(6)7/h3,5H,2H2,1H3,(H,6,7) |
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|StdInChI = 1S/C4H8O3/c1-3(5)2-4(6)7/h3,5H,2H2,1H3,(H,6,7) |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = WHBMMWSBFZVSSR-UHFFFAOYSA-N |
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|StdInChIKey = WHBMMWSBFZVSSR-UHFFFAOYSA-N |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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|CASNo_Ref = {{cascite|correct|CAS}} |
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| CASNo = 300-85-6 |
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|CASNo = 300-85-6 |
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| PubChem = 441 |
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|PubChem = 441 |
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| IUPHAR_ligand = 1593 |
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|IUPHAR_ligand = 1593 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 428 |
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|ChemSpiderID = 428 |
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|ChEBI_Ref = {{ebicite|correct|EBI}} |
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| ChEBI = 20067 |
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|ChEBI = 20067 |
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| SMILES = O=C(O)CC(O)C |
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|Beilstein = 773861 |
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| MeSHName = beta-Hydroxybutyrate |
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|UNII_Ref = {{fdacite|correct|FDA}} |
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}} |
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|UNII = TZP1275679 |
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| Section2 = {{Chembox Properties |
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|KEGG = C01089 |
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| C=4|H=8|O=3 |
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|3DMet = B00239 |
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| Appearance = |
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|SMILES = O=C(O)CC(O)C |
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| Density = |
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|MeSHName = beta-Hydroxybutyrate |
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| MeltingPt = |
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}} |
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| BoilingPt = |
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|Section2={{Chembox Properties |
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}} |
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|C=4 | H=8 | O=3 |
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| Section3 = {{Chembox Hazards |
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|Appearance = white solid |
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| Solubility = |
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|MeltingPt = 44-46 |
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| MainHazards = |
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}} |
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| FlashPt = |
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|Section3={{Chembox Related |
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| Autoignition = |
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|OtherAnions = ] |
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}} |
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|OtherFunction_label = ]s |
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| Section4 = {{Chembox Related |
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|OtherFunction = ]<br />]<br />]<br />]<br />]<br />]<br />]<br />]<br />] |
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| OtherAnions = ] |
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|OtherCompounds = ]<br />]<br />]<br />]<br />]<br />] |
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| Function = ]s |
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}} |
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| OtherFunctn = ]<br />]<br />]<br />]<br />]<br />] |
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| OtherCpds = ]<br />]<br />]<br />]<br />]<br />] |
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}} |
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}} |
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'''''beta''-Hydroxybutyric acid''' (also known as '''''beta''-hydroxybutyrate''' or '''3-hydroxybutyric acid''') is a ]. It is a ] compound having two ], <small>D</small>-3-hydroxybutyric acid and <small>L</small>-3-hydroxybutyric acid. Like the other ketone bodies (] and ]), levels of ''beta''-hydroxybutyrate are raised in ]. In humans, ''beta''-hydroxybutyrate is synthesized in the ] from ] and can be used as an energy source by the brain when blood ] is low.<ref>{{cite journal|author=O. E. Owen et al.|title=Brain Metabolism during Fasting|journal=The Journal of Clinical Investigation|volume=46|issue=10|year=1967|pages=1589–1595|pmid=6061736|doi=10.1172/JCI105650|pmc=292907}}</ref> ] patients can have their ketone levels tested via urine or blood to indicate ]. In alcoholic ketoacidosis, this ketone body is produced in greatest concentration. Both types of ketoacidosis result in an increase B-Hydroxybutyrate to ] ratio, resulting in TCA cycle stalling and shifting of glucose towards ketone body production. |
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'''β-Hydroxybutyric acid''', also known as '''3-hydroxybutyric acid''' or '''BHB''', is an organic compound and a ] with the ] CH<sub>3</sub>CH(OH)CH<sub>2</sub>CO<sub>2</sub>H; its ] is '''β-hydroxybutyrate''', also known as '''3-hydroxybutyrate'''. β-Hydroxybutyric acid is a ] compound with two ]: <small>D</small>-β-hydroxybutyric acid and <small>L</small>-β-hydroxybutyric acid. Its oxidized and polymeric derivatives occur widely in nature. In humans, <small>D</small>-β-hydroxybutyric acid is one of two primary ] ]s of ] (HCA<sub>2</sub>), a {{nowrap|]}} ] (GPCR).<ref name="IUPHAR's comprehensive 2011 review on HCARs">{{cite journal | vauthors = Offermanns S, Colletti SL, Lovenberg TW, Semple G, Wise A, IJzerman AP | title = International Union of Basic and Clinical Pharmacology. LXXXII: Nomenclature and Classification of Hydroxy-carboxylic Acid Receptors (GPR81, GPR109A, and GPR109B) | journal = Pharmacological Reviews | volume = 63 | issue = 2 | pages = 269–290 | date = June 2011 | pmid = 21454438 | doi = 10.1124/pr.110.003301 | doi-access = free }}</ref><ref name="IUPHAR-DB HCAR family page">{{cite web |vauthors = Offermanns S, Colletti SL, IJzerman AP, Lovenberg TW, Semple G, Wise A, Waters MG |title=Hydroxycarboxylic acid receptors |url=http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=48 |website=IUPHAR/BPS Guide to Pharmacology |publisher=International Union of Basic and Clinical Pharmacology |access-date=13 July 2018}}</ref> |
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==Biosynthesis== |
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In industry, it can also be used for the synthesis of ], such as ]. This polymer can be produced biologically by the bacteria '']''.<ref>{{cite journal | author = Yoshiharu Doi, Masao Kunioka, Yoshiyuki Nakamura, Kazuo Soga | title = Nuclear magnetic resonance studies on unusual bacterial copolyesters of 3-hydroxybutyrate and 4-hydroxybutyrate | journal = Macromolecules | year = 1988 | volume = 21 | issue = 9 | pages = 2722–2727 | doi=10.1021/ma00187a012}}</ref> |
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In humans, {{nowrap|<small>D</small>-β-hydroxybutyrate}} can be synthesized in the ] via the ] (e.g., ]), ], and ]s through a series of reactions that metabolize these compounds into ], which is the first ] that is produced in the ] state. The biosynthesis of {{nowrap|<small>D</small>-β-hydroxybutyrate}} from acetoacetate is catalyzed by the ] ]. |
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Butyrate can also be metabolized into {{nowrap|<small>D</small>-β-hydroxybutyrate}} via a second ] that does not involve acetoacetate as a metabolic intermediate. This metabolic pathway is as follows:<ref name="Butyrate metabolism">{{cite web|title=Butanoate metabolism - Reference pathway|url=http://www.genome.jp/kegg-bin/show_pathway?map00650|website=Kyoto Encyclopedia of Genes and Genomes|publisher=Kanehisa Laboratories|date=1 November 2017|access-date=1 February 2018}}</ref> |
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==See also== |
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:butyrate→]→]→]→]→{{nowrap|<small>D</small>-β-}}({{nowrap|<small>D</small>-β-hydroxybutyryloxy}}){{nowrap|-butyrate}}→{{nowrap|<small>D</small>-β-hydroxybutyrate}} |
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The last reaction in this metabolic pathway, which involves the conversion of {{nowrap|<small>D</small>-β-}}({{nowrap|<small>D</small>-β-hydroxybutyryloxy}}){{nowrap|-butyrate}} into {{nowrap|<small>D</small>-β-hydroxybutyrate}}, is catalyzed by the ] enzyme.<ref name="Butyrate metabolism" /> |
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The concentration of β-hydroxybutyrate in human blood plasma, as with other ], increases through ].<ref name="Medscape2015">{{Cite journal |url= https://emedicine.medscape.com/article/2087381-overview#a4|title = Beta-Hydroxybutyrate |vauthors = Perelas A, Staros EB |date=October 30, 2015 |website= Medscape |publisher = WebMD LLC. |access-date= February 8, 2017}}</ref> This elevated β-hydroxybutyrate level is naturally expected, as β-hydroxybutyrate is formed from acetoacetate. The compound can be used as an energy source by the brain and skeletal muscle when ] is low.<ref>{{cite journal | vauthors = Owen OE, Morgan AP, Kemp HG, Sullivan JM, Herrera MG, Cahill GF | title = Brain metabolism during fasting | journal = The Journal of Clinical Investigation | volume = 46 | issue = 10 | pages = 1589–1595 | date = October 1967 | pmid = 6061736 | pmc = 292907 | doi = 10.1172/JCI105650 }}</ref><ref>{{cite journal | vauthors = Evans E, Walhin JP, Hengist A, Betts JA, Dearlove DJ, Gonzalez JT | title = Ketone monoester ingestion increases postexercise serum erythropoietin concentrations in healthy men | journal = American Journal of Physiology. Endocrinology and Metabolism | volume = 324 | issue = 1 | pages = E56–E61 | date = January 2023 | pmid = 36449571 | pmc = 9870573 | doi = 10.1152/ajpendo.00264.2022 }}</ref><ref>{{cite journal | vauthors = Cahill GF | title = Fuel metabolism in starvation | journal = Annual Review of Nutrition | volume = 26 | issue = 1 | pages = 1–22 | date = 2006-08-01 | pmid = 16848698 | doi = 10.1146/annurev.nutr.26.061505.111258 }}</ref><ref>{{cite journal | vauthors = Mikkelsen KH, Seifert T, Secher NH, Grøndal T, van Hall G | title = Systemic, cerebral and skeletal muscle ketone body and energy metabolism during acute hyper-D-β-hydroxybutyratemia in post-absorptive healthy males | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 100 | issue = 2 | pages = 636–643 | date = February 2015 | pmid = 25415176 | doi = 10.1210/jc.2014-2608 | doi-access = free }}</ref> ] patients can have their ketone levels tested via urine or blood to indicate ]. In ], this ketone body is produced in greatest concentration. Ketogenesis occurs if ] in the liver cells is depleted, a circumstance created by reduced carbohydrate intake (through diet or starvation); prolonged, excessive ] consumption; and/or insulin deficiency. Because oxaloacetate is crucial for entry of ] into the TCA cycle, the rapid production of acetyl-CoA from fatty acid oxidation in the absence of ample oxaloacetate overwhelms the decreased capacity of the TCA cycle, and the resultant excess of acetyl-CoA is shunted towards ketone body production.{{citation needed|date=June 2016}} |
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==References== |
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{{reflist}} |
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{{Leucine metabolism in humans|note=yes|align=left|caption=Acetoacetate, the metabolic precursor of β-hydroxybutyrate, is a metabolite of ]s, ]s such as ]<ref name="HMG biosynthesis" /> and ],<ref name="HMG biosynthesis">{{cite web|title=Valine, leucine and isoleucine degradation - Reference pathway|url=http://www.genome.jp/kegg-bin/show_pathway?map00280+C00356|website=Kyoto Encyclopedia of Genes and Genomes|publisher=Kanehisa Laboratories|date=27 January 2016|access-date=1 February 2018}}</ref> and ]}}{{clear}} |
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==Biological activity== |
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{{expand section|transporter proteins<ref name="β-D-hydroxybutyric acid IUPHAR" /> that move it across lipid membranes|date=February 2018|small=no}} |
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<small>D</small>-β-Hydroxybutyric acid, along with ], are the two primary ] ]s of ] (HCA<sub>2</sub>), a {{nowrap|]}} ].<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 ] into the ].<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 |doi-access=free }}</ref> Levels of β-hydroxybutyric acid increase in the ], ], ], ], and other tissues with ], ], ], and ]s.<ref name="pmid27253067" /> The compound has been found to act as a ].<ref name="pmid27253067" /> Through inhibition of the HDAC class I ]s ] and ], β-hydroxybutyric acid has been found to increase ] (BDNF) levels and ] ] in the ].<ref name="pmid27253067" /> Moreover, a rodent study found that prolonged exercise increases plasma β-hydroxybutyrate concentrations, which induces ] of the BDNF gene in the hippocampus.<ref name="pmid27253067" /> These findings may have clinical relevance in the treatment of ], ], and ].<ref name="pmid27253067"/> |
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In ] patients on the ketogenic diet, blood β-hydroxybutyrate levels correlate best with degree of ] control. The threshold for optimal ] effect appears to be approximately 4 ].<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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==Laboratory and industrial chemistry== |
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β-Hydroxybutyric acid is the precursor to polyesters, which are ]. This polymer, ], is also ] by the bacteria '']''.<ref>{{cite journal | vauthors = Doi Y, Kunioka M, Nakamura Y, Soga K | title = Nuclear magnetic resonance studies on unusual bacterial copolyesters of 3-hydroxybutyrate and 4-hydroxybutyrate | journal = Macromolecules | year = 1988 | volume = 21 | issue = 9 | pages = 2722–2727 | doi=10.1021/ma00187a012|bibcode=1988MaMol..21.2722D}}</ref> |
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β-Hydroxybutyrate can be extracted from poly(3-hydroxybutyrate) by acid ].<ref>{{cite journal | vauthors = Seebach D, Beck AK, Breitschuh R, Job K | title = Direct Degradation of the Biopolymer Poly[(''R'')-3-Hydroxybutrric Acid to (''R'')-3-Hydroxybutanoic Acid and Its Methyl Ester | journal = Organic Syntheses | date = April 1993 | volume = 71 | page = 39 | doi = 10.15227/orgsyn.071.0039}}</ref> |
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The concentration of {{nowrap|β-hydroxybutyrate}} in ] is measured through a test that uses ], with ] as an electron-accepting ]. The conversion of {{nowrap|β-hydroxybutyrate}} to acetoacetate, which is catalyzed by this enzyme, reduces the NAD<sup>+</sup> to ], generating an electrical change; the magnitude of this change can then be used to extrapolate the amount of {{nowrap|β-hydroxybutyrate}} in the sample. |
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== See also == |
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* ] |
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* ] (HMB) |
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* ] |
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* ] |
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==Notes== |
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{{Reflist|group=note}} |
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== References == |
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{{Reflist}} |
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{{Cholesterol and steroid intermediates}} |
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{{Cholesterol and steroid intermediates}} |
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{{HDAC inhibitors}} |
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{{DEFAULTSORT:Hydroxybutyric acid, beta-}} |
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{{DEFAULTSORT:Hydroxybutyric acid, beta-}} |
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