 | |
| Names | |
|---|---|
| Preferred IUPAC name 3-Hydroxybutanoic acid | |
| Identifiers | |
| |
3D model (JSmol) | |
| 773861 | |
| ChEBI | |
| ChEMBL | |
| ChemSpider |
|
| ECHA InfoCard | 100.005.546 |
| KEGG | |
| MeSH | beta-Hydroxybutyrate |
| UNII | |
| |
| |
| Properties | |
| C4H8O3 | |
| Molar mass | 104.105 g·mol−1 |
| Appearance | white solid |
| Melting point | 44-46 |
| Related compounds | |
Otheranions | hydroxybutyrate |
Relatedcarboxylic acids | propionic acid lactic acid 3-hydroxypropanoic acid malonic acid β-hydroxyvaleric acid butyric acid β-methylbutyric acid β-hydroxy β-methylbutyric acid crotonic acid |
Related compounds | erythrose threose 1,2-butanediol 1,3-butanediol 2,3-butanediol 1,4-butanediol |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
β-Hydroxybutyric acid, also known as3-hydroxybutyric acid orBHB, is an organic compound and abeta hydroxy acid with thechemical formula CH3CH(OH)CH2CO2H; itsconjugate base isβ-hydroxybutyrate, also known as3-hydroxybutyrate. β-Hydroxybutyric acid is achiral compound with twoenantiomers:D-β-hydroxybutyric acid andL-β-hydroxybutyric acid. Its oxidized and polymeric derivatives occur widely in nature. In humans,D-β-hydroxybutyric acid is one of two primaryendogenousagonists ofhydroxycarboxylic acid receptor 2 (HCA2), aGi/o-coupledG protein-coupled receptor (GPCR).[1][2]
In humans,D-β-hydroxybutyrate can be synthesized in theliver via themetabolism of fatty acids (e.g.,butyrate),β-hydroxyβ-methylbutyrate, andketogenic amino acids through a series of reactions that metabolize these compounds intoacetoacetate, which is the firstketone body that is produced in thefasting state. The biosynthesis ofD-β-hydroxybutyrate from acetoacetate is catalyzed by theβ-hydroxybutyrate dehydrogenaseenzyme.
Butyrate can also be metabolized intoD-β-hydroxybutyrate via a secondmetabolic pathway that does not involve acetoacetate as a metabolic intermediate. This metabolic pathway is as follows:[3]
The last reaction in this metabolic pathway, which involves the conversion ofD-β-(D-β-hydroxybutyryloxy)-butyrate intoD-β-hydroxybutyrate, is catalyzed by thehydroxybutyrate-dimer hydrolase enzyme.[3]
The concentration of β-hydroxybutyrate in human blood plasma, as with otherketone bodies, increases throughketosis.[4] 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 whenblood glucose is low.[5][6][7][8]Diabetic patients can have their ketone levels tested via urine or blood to indicatediabetic ketoacidosis. Inalcoholic ketoacidosis, this ketone body is produced in greatest concentration. Ketogenesis occurs ifoxaloacetate in the liver cells is depleted, a circumstance created by reduced carbohydrate intake (through diet or starvation); prolonged, excessivealcohol consumption; and/or insulin deficiency. Because oxaloacetate is crucial for entry ofacetyl-CoA 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]
 Muscle:α-Ketoisocaproate (α-KIC) Liver:α-Ketoisocaproate (α-KIC) Excreted in urine (10–40%) β-Hydroxy β-methylglutaryl-CoA (HMG-CoA) β-Methylcrotonyl-CoA (MC-CoA) β-Methylglutaconyl-CoA (MG-CoA) Unknown enzyme  |
![[icon]](/mt/?noimg=&dark=on&url=https%3a%2f%2fen.wikipedia.org%2fwiki%2fFile%3aWiki_letter_w_cropped.svg) | This sectionneeds expansion with: transporter proteins[12] that move it across lipid membranes. You can help byadding to it.(February 2018) |
D-β-Hydroxybutyric acid, along withbutyric acid, are the two primaryendogenousagonists ofhydroxycarboxylic acid receptor 2 (HCA2), aGi/o-coupledGPCR.[1][2][12]
β-Hydroxybutyric acid is able to cross theblood-brain-barrier into thecentral nervous system.[13] Levels of β-hydroxybutyric acid increase in theliver,heart,muscle,brain, and other tissues withexercise,calorie restriction,fasting, andketogenic diets.[13] The compound has been found to act as ahistone deacetylase (HDAC) inhibitor.[13] Through inhibition of the HDAC class IisoenzymesHDAC2 andHDAC3, β-hydroxybutyric acid has been found to increasebrain-derived neurotrophic factor (BDNF) levels andTrkBsignaling in thehippocampus.[13] Moreover, a rodent study found that prolonged exercise increases plasma β-hydroxybutyrate concentrations, which inducespromoters of the BDNF gene in the hippocampus.[13] These findings may have clinical relevance in the treatment ofdepression,anxiety, andcognitive impairment.[13]
Inepilepsy patients on the ketogenic diet, blood β-hydroxybutyrate levels correlate best with degree ofseizure control. The threshold for optimalanticonvulsant effect appears to be approximately 4 mmol/L.[14]
β-Hydroxybutyric acid is the precursor to polyesters, which arebiodegradable plastics. This polymer,poly(3-hydroxybutyrate), is alsonaturally produced by the bacteriaAlcaligenes eutrophus.[15]
β-Hydroxybutyrate can be extracted from poly(3-hydroxybutyrate) by acidhydrolysis.[16]
The concentration ofβ-hydroxybutyrate inblood plasma is measured through a test that usesβ-hydroxybutyrate dehydrogenase, withNAD+ as an electron-acceptingcofactor. The conversion ofβ-hydroxybutyrate to acetoacetate, which is catalyzed by this enzyme, reduces the NAD+ toNADH, generating an electrical change; the magnitude of this change can then be used to extrapolate the amount ofβ-hydroxybutyrate in the sample.
Metabolic impairment diverts methylcrotonyl CoA to 3-hydroxyisovaleryl CoA in a reaction catalyzed by enoyl-CoA hydratase (22, 23). 3-Hydroxyisovaleryl CoA accumulation can inhibit cellular respiration either directly or via effects on the ratios of acyl CoA:free CoA if further metabolism and detoxification of 3-hydroxyisovaleryl CoA does not occur (22). The transfer to carnitine by 4 carnitine acyl-CoA transferases distributed in subcellular compartments likely serves as an important reservoir for acyl moieties (39–41). 3-Hydroxyisovaleryl CoA is likely detoxified by carnitine acetyltransferase producing 3HIA-carnitine, which is transported across the inner mitochondrial membrane (and hence effectively out of the mitochondria) via carnitine-acylcarnitine translocase (39). 3HIA-carnitine is thought to be either directly deacylated by a hydrolase to 3HIA or to undergo a second CoA exchange to again form 3-hydroxyisovaleryl CoA followed by release of 3HIA and free CoA by a thioesterase.
