β-Hydroxybutyric acid

Source: Wikipedia, the free encyclopedia.
Not to be confused with β-Hydroxy β-methylbutyric acid.
β-Hydroxybutyric acid
Names
Preferred IUPAC name
3-Hydroxybutanoic acid
Identifiers
3D model (
JSmol
)
3DMet
773861
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard
 100.005.546 Edit this at Wikidata
IUPHAR/BPS
KEGG
MeSH beta-Hydroxybutyrate
UNII
  • InChI=1S/C4H8O3/c1-3(5)2-4(6)7/h3,5H,2H2,1H3,(H,6,7) checkY
    Key: WHBMMWSBFZVSSR-UHFFFAOYSA-N checkY
  • InChI=1/C4H8O3/c1-3(5)2-4(6)7/h3,5H,2H2,1H3,(H,6,7)
    Key: WHBMMWSBFZVSSR-UHFFFAOYAO
  • O=C(O)CC(O)C
  • CC(CC(=O)O)O
Properties
C4H8O3
Molar mass 104.105 g·mol−1
Appearance white solid
Melting point 44-46
Related compounds
Other anions
hydroxybutyrate
β-hydroxy β-methylbutyric acid
Related compounds
1,4-butanediol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

β-Hydroxybutyric acid, also known as 3-hydroxybutyric acid or BHB, is an organic compound and a

endogenous agonists of hydroxycarboxylic acid receptor 2 (HCA2), a Gi/o-coupled G protein-coupled receptor (GPCR).[1][2]

Biosynthesis

In humans, D-β-hydroxybutyrate can be synthesized in the

β-hydroxybutyrate dehydrogenase enzyme
.

Butyrate can also be metabolized into D-β-hydroxybutyrate via a second metabolic pathway that does not involve acetoacetate as a metabolic intermediate. This metabolic pathway is as follows:[3]

butyrate→
poly-β-hydroxybutyrate
→D-β-(D-β-hydroxybutyryloxy)-butyrate→D-β-hydroxybutyrate

The last reaction in this metabolic pathway, which involves the conversion of D-β-(D-β-hydroxybutyryloxy)-butyrate into D-β-hydroxybutyrate, is catalyzed by the hydroxybutyrate-dimer hydrolase enzyme.[3]

The concentration of β-hydroxybutyrate in human blood plasma, as with other

oxaloacetate in the liver cells is depleted, a circumstance created by reduced carbohydrate intake (through diet or starvation); prolonged, excessive alcohol consumption; and/or insulin deficiency. Because oxaloacetate is crucial for entry of acetyl-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
]


Diagram of leucine, HMB, and isovaleryl-CoA metabolism in humans
α-Ketoglutarate
Glutamate
Glutamate
Pyruvate
α-Ketoisocaproate
(α-KIC)
α-Ketoisocaproate
(α-KIC)
mitochondria
)
Excreted
in urine
(10–40%)


(
HMG-CoA
lyase
HMG-CoA 
synthase
Unknown
enzyme
β-Hydroxybutyrate
Acetoacetate
Mevalonate
The image above contains clickable links
Acetoacetate, the metabolic precursor of β-hydroxybutyrate, is a metabolite of
β-hydroxy β-methylbutyrate

Biological activity

D-β-Hydroxybutyric acid, along with

GPCR.[1][2][12]

β-Hydroxybutyric acid is able to cross the

TrkB signaling in the hippocampus.[13] Moreover, a rodent study found that prolonged exercise increases plasma β-hydroxybutyrate concentrations, which induces promoters of the BDNF gene in the hippocampus.[13] These findings may have clinical relevance in the treatment of depression, anxiety, and cognitive impairment.[13]

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.[14]

Laboratory and industrial chemistry

β-Hydroxybutyric acid is the precursor to polyesters, which are

Alcaligenes eutrophus.[15]

β-Hydroxybutyrate can be extracted from poly(3-hydroxybutyrate) by acid hydrolysis.[16]

The concentration of β-hydroxybutyrate in

β-hydroxybutyrate dehydrogenase, with NAD+ as an electron-accepting cofactor. The conversion of β-hydroxybutyrate to acetoacetate, which is catalyzed by this enzyme, reduces the NAD+ to NADH
, generating an electrical change; the magnitude of this change can then be used to extrapolate the amount of β-hydroxybutyrate in the sample.

See also

Notes

  1. ^ This reaction is catalyzed by an unknown thioesterase enzyme.[9][10]

References

  1. ^
    PMID 21454438
    .
  2. ^ a b Offermanns S, Colletti SL, IJzerman AP, Lovenberg TW, Semple G, Wise A, Waters MG. "Hydroxycarboxylic acid receptors". IUPHAR/BPS Guide to Pharmacology. International Union of Basic and Clinical Pharmacology. Retrieved 13 July 2018.
  3. ^ a b "Butanoate metabolism - Reference pathway". Kyoto Encyclopedia of Genes and Genomes. Kanehisa Laboratories. 1 November 2017. Retrieved 1 February 2018.
  4. ^ Perelas A, Staros EB (October 30, 2015). "Beta-Hydroxybutyrate". Medscape. WebMD LLC. Retrieved February 8, 2017.
  5. PMID 6061736
    .
  6. PMID 36449571
    .
  7. PMID 16848698
    .
  8. PMID 25415176
    .
  9. ^ "KEGG Reaction: R10759". Kyoto Encyclopedia of Genes and Genomes. Kanehisa Laboratories. Retrieved 24 June 2016.
  10. PMID 21918059
    . 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.
  11. ^ a b "Valine, leucine and isoleucine degradation - Reference pathway". Kyoto Encyclopedia of Genes and Genomes. Kanehisa Laboratories. 27 January 2016. Retrieved 1 February 2018.
  12. ^ a b "β-D-hydroxybutyric acid: Biological activity". IUPHAR/BPS Guide to Pharmacology. International Union of Basic and Clinical Pharmacology. Retrieved 5 February 2018.
  13. ^
    PMID 27253067
    .
  14. S2CID 46659339
    .
  15. doi:10.1021/ma00187a012
    .
  16. doi:10.15227/orgsyn.071.0039
    .
Retrieved from "https://en.wikipedia.org/w/index.php?title=Β-Hydroxybutyric_acid&oldid=1194115582"