Β-Alanine

{{Lowercase title}} {{chembox | Watchedfields = changed | verifiedrevid = 443667077 | Name=β-Alanine | ImageFile = Beta-alanine structure.svg | ImageSize = 180 | ImageAlt = Skeletal formula of beta alanine | ImageFile1 = | ImageSize1 = 180 | ImageAlt1 = | ImageClass = skin-invert | IUPACName = β-Alanine | SystematicName = 3-Aminopropanoic acid | OtherNames = 3-Aminopropionic acid |Section1={{Chembox Identifiers | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 11P2JDE17B | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D07561 | InChI = 1/C3H7NO2/c4-2-1-3(5)6/h1-2,4H2,(H,5,6) | InChIKey = UCMIRNVEIXFBKS-UHFFFAOYAL | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 297569 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C3H7NO2/c4-2-1-3(5)6/h1-2,4H2,(H,5,6) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = UCMIRNVEIXFBKS-UHFFFAOYSA-N | CASNo = 107-95-9 | CASNo_Ref = {{cascite|correct|CAS}} | EC_number = 203-536-5 | PubChem = 239 | IUPHAR_ligand = 2365 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 234 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 16958 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB03107 | SMILES = O=C(O)CCN }} |Section2={{Chembox Properties | Properties_ref = <ref>{{Merck11th|196}}.</ref><ref>{{RubberBible62nd|page=C-83}}.</ref> | C=3 | H=7 | N=1 | O=2 | Appearance = white bipyramidal crystals | Odor = odorless | Density = 1.437 g/cm3 (19 °C) | MeltingPtC = 207 | MeltingPt_notes = (decomposes) | BoilingPt = | Solubility = 54.5 g/100 mL | SolubleOther = soluble in methanol. Insoluble in diethyl ether, acetone | LogP = −3.05 | pKa = {{ubl | 3.55 (carboxyl; H2O) | 10.24 (amino; H2O)<ref name="CRC97">{{cite book | editor= Haynes, William M. | year = 2016 | title = CRC Handbook of Chemistry and Physics | edition = 97th | publisher = CRC Press | isbn = 978-1498754286 | pages=5–88 | title-link = CRC Handbook of Chemistry and Physics }}</ref> }} }} |Section3={{Chembox Hazards | ExternalSDS = [http://www.hmdb.ca/system/metabolites/msds/000/000/041/original/HMDB00056.pdf?1358893572] | MainHazards = Irritant | NFPA-H = 2 | NFPA-F = 1 | NFPA-R = 0 | FlashPtC = | AutoignitionPt = | LD50 = 1000 mg/kg (rat, oral) }} }}

'''β-Alanine''' ('''''beta''-alanine''') is a naturally occurring beta amino acid. Beta amino acids are amino acids in which the amino group is attached to the β-carbon atom (i.e. the carbon atom two carbon atoms away from the carboxylate group) instead of the more usual α-carbon atom for alanine (α-alanine). The IUPAC name for β-alanine is '''3-aminopropanoic acid'''. Unlike its counterpart α-alanine, β-alanine has no stereocenter.

==Biosynthesis and industrial route== In terms of its biosynthesis, it is formed by the degradation of dihydrouracil and carnosine. β-Alanine ethyl ester is the ethyl ester which hydrolyses within the body to form β-alanine.<ref>{{cite journal|last1=Wright|first1=Margaret Robson|title=Arrhenius parameters for the acid hydrolysis of esters in aqueous solution. Part I. Glycine ethyl ester, β-alanine ethyl ester, acetylcholine, and methylbetaine methyl ester|journal=Journal of the Chemical Society B: Physical Organic|date=1969|pages=707–710|doi=10.1039/J29690000707}}</ref> It is produced industrially by the reaction of ammonia with β-propiolactone.<ref name=Ullmann>{{Ullmann|doi=10.1002/14356007.a13_507|title=Hydroxycarboxylic Acids, Aliphatic|year=2005|last1=Miltenberger|first1=Karlheinz|isbn=3527306730}}</ref>

Sources for β-alanine includes pyrimidine catabolism of cytosine and uracil.

==Biochemical function== β-Alanine residues are rare. It is a component of the peptides carnosine and anserine and also of pantothenic acid (vitamin B5), which itself is a component of coenzyme A. β-alanine is metabolized into acetic acid.

=== Precursor of carnosine === β-Alanine is the rate-limiting precursor of carnosine, which is to say carnosine levels are limited by the amount of available β-alanine, not histidine.<ref name="pharmacistanswers.com">{{cite web|url=http://pharmacistanswers.com/beta-alanine-supplementation-for-exercise-performance.html|title=Beta-Alanine Supplementation For Exercise Performance|access-date=21 September 2018|archive-date=20 June 2017|archive-url=https://web.archive.org/web/20170620082252/http://www.pharmacistanswers.com/beta-alanine-supplementation-for-exercise-performance.html|url-status=dead}}</ref> Supplementation with β-alanine has been shown to increase the concentration of carnosine in muscles, decrease fatigue in athletes, and increase total muscular work done.<ref>{{cite journal|vauthors=Derave W, Ozdemir MS, Harris R, Pottier A, Reyngoudt H, Koppo K, Wise JA, Achten E |title=Beta-alanine supplementation augments muscle carnosine content and attenuates fatigue during repeated isokinetic contraction bouts in trained sprinters |journal=J Appl Physiol |date=August 9, 2007 |pmid = 17690198 |doi=10.1152/japplphysiol.00397.2007 |volume=103|issue=5 |pages=1736–43 |s2cid=6990201 }}</ref><ref name="Hill2007">{{cite journal|vauthors=Hill CA, Harris RC, Kim HJ, Harris BD, Sale C, Boobis LH, Kim CK, Wise JA |title=Influence of beta-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity |journal= Amino Acids |year=2007 |issue=2 |volume=32 |pages=225–33 |pmid =16868650 |doi=10.1007/s00726-006-0364-4 |s2cid=23988054 }}</ref> Simply supplementing with carnosine is not as effective as supplementing with β-alanine alone since carnosine, when taken orally, is broken down during digestion to its components, histidine (which people usually already have enough of from regular protein consumption) and β-alanine. Hence, by weight, only about 40% of the dose is available as β-alanine.<ref name="pharmacistanswers.com"/>

thumb|left|200px|Comparison of β-alanine (right) with the more customary, chiral, α-amino acid, L-α-alanine (left)

Because β-alanine dipeptides are not incorporated into proteins, they can be stored at relatively high concentrations. Occurring at 17–25 mmol/kg (dry muscle),<ref>{{Cite journal | doi = 10.1007/BF00376439 | pmid = 1735411 | last1 = Mannion | first1 = AF | last2 = Jakeman | first2 = PM | last3 = Dunnett | first3 = M | last4 = Harris | first4 = RC | last5 = Willan | first5 = PLT | year = 1992 | title = Carnosine and anserine concentrations in the quadriceps femoris muscle of healthy humans | journal = Eur. J. Appl. Physiol | volume = 64 | issue = 1| pages = 47–50 | s2cid = 24590951 }}</ref> carnosine (β-alanyl-L-histidine) is an important intramuscular buffer, constituting 10-20% of the total buffering capacity in type I and II muscle fibres. In carnosine, the p''K''a of the imidazolium group is 6.83, which is ideal for buffering.<ref>{{Cite journal | last1 = Bate-Smith | first1 = EC | year = 1938 | title = The buffering of muscle in rigor: protein, phosphate and carnosine | journal = Journal of Physiology | volume = 92 | issue = 3| pages = 336–343 | pmid = 16994977 | pmc = 1395289 | doi = 10.1113/jphysiol.1938.sp003605 }}</ref>

=== Receptors === Even though much weaker than glycine (and, thus, with a debated role as a physiological transmitter), β-alanine is an agonist next in activity to the cognate ligand glycine itself, for strychnine-sensitive inhibitory glycine receptors (GlyRs) (the agonist order: glycine ≫ β-alanine > taurine ≫ alanine, L-serine > proline).<ref>''Encyclopedia of Life Sciences'' Amino Acid Neurotransmitters. Jeremy M Henley, 2001 John Wiley & Sons, Ltd. {{doi|10.1038/npg.els.0000010}}, Article Online Posting Date: April 19, 2001</ref>

β-alanine has five known receptor sites, including GABA-A, GABA-C a co-agonist site (with glycine) on NMDA receptors, the aforementioned GlyR site, and blockade of GAT protein-mediated glial GABA uptake, making it a putative "small molecule neurotransmitter."<ref>{{cite journal |vauthors=Tiedje KE, Stevens K, Barnes S, Weaver DF |title=Beta-alanine as a small molecule neurotransmitter |journal=Neurochem Int |volume=57 |issue=3 |pages=177–88 |date=October 2010 |pmid=20540981 |doi=10.1016/j.neuint.2010.06.001 |s2cid=7814845 |url=}}</ref>

== Athletic performance enhancement == There is evidence that β-alanine supplementation can increase exercise and cognitive performance,<ref name=quesnale>{{cite journal |vauthors=Quesnele JJ, Laframboise MA, Wong JJ, Kim P, Wells GD |title=The effects of beta-alanine supplementation on performance: a systematic review of the literature |journal=Int J Sport Nutr Exerc Metab |volume=24 |issue=1 |pages=14–27 |year=2014 |pmid=23918656 |doi=10.1123/ijsnem.2013-0007 |type=Systematic review}}</ref><ref name=hoffman>{{cite journal |vauthors=Hoffman JR, Stout JR, Harris RC, Moran DS |title=β-Alanine supplementation and military performance |journal=Amino Acids |volume=47 |issue=12 |pages=2463–74 |year=2015 |pmid=26206727 |pmc=4633445 |doi=10.1007/s00726-015-2051-9 }}</ref><ref name=hobson>{{cite journal |last1=Hobson |first1=R. M. |last2=Saunders |first2=B. |last3=Ball |first3=G. |last4=Harris |first4=R. C. |last5=Sale |first5=C. |title=Effects of β-alanine supplementation on exercise performance: a meta-analysis |journal=Amino Acids|date=9 December 2016 |volume=43 |issue=1 |pages=25–37|doi=10.1007/s00726-011-1200-z|pmc=3374095|issn=0939-4451|pmid=22270875}}</ref><ref name="issn2015"/> for some sporting modalities,<ref>{{cite journal |title=Ergogenic Effects of β-Alanine Supplementation on Different Sports Modalities: Strong Evidence or Only Incipient Findings? |first1=Gabriel M P |last1=Brisola |first2=Alessandro M |last2=Zagatto |journal=The Journal of Strength and Conditioning Research |year=2019 |volume=33 |issue=1 |pages=253–282 |pmid= 30431532 |doi= 10.1519/JSC.0000000000002925 |s2cid=53441737 }}</ref> and exercises within a 0.5–10 min time frame.<ref>{{cite journal |title=β-alanine supplementation to improve exercise capacity and performance: a systematic review and meta-analysis FREE |author1=Bryan Saunders |author2=Kirsty Elliott-Sale |author3=Guilherme G Artioli1 |author4=Paul A Swinton |author5=Eimear Dolan |author6=Hamilton Roschel |author7=Craig Sale |author8=Bruno Gualano|journal=British Journal of Sports Medicine |year=2017 |volume=51 |issue=8 |pages=658–669 |pmid=27797728 |doi=10.1136/bjsports-2016-096396 |s2cid=25496458 |doi-access=free|hdl=10059/1913 |hdl-access=free }}</ref> β-alanine is converted within muscle cells into carnosine, which acts as a buffer for the lactic acid produced during high-intensity exercises, and helps delay the onset of neuromuscular fatigue.<ref name=hobson /><ref>{{cite journal |journal=Med Sci Sports Exerc |date=June 2010 |volume=42 |issue=6 |pages=1162–73 |title=Role of beta-alanine supplementation on muscle carnosine and exercise performance |author1=Guilherme Giannini Artioli |author2=Bruno Gualano |author3=Abbie Smith |author4=Jeffrey Stout |author5=Antonio Herbert Lancha Jr. |doi=10.1249/MSS.0b013e3181c74e38 |pmid=20479615|doi-access=free }}</ref>

Ingestion of β-alanine can cause paraesthesia, reported as a tingling sensation, in a dose-dependent fashion.<ref name="issn2015">{{cite journal |vauthors=Trexler ET, Smith-Ryan AE, Stout JR, Hoffman JR, Wilborn CD, Sale C, Kreider RB, Jäger R, Earnest CP, Bannock L, Campbell B, Kalman D, Ziegenfuss TN, Antonio J |title=International society of sports nutrition position stand: Beta-Alanine |journal=J Int Soc Sports Nutr |volume=12 |pages=30 |year=2015 |pmid=26175657 |pmc=4501114 |doi=10.1186/s12970-015-0090-y |doi-access=free |type=Review}}</ref> Aside from this, no important adverse effect of β-alanine has been reported, however, there is also no information on the effects of its long-term usage or its safety in combination with other supplements, and caution on its use has been advised.<ref name=quesnale /><ref name=hoffman /> Furthermore, many studies have failed to test for the purity of the supplements used and check for the presence of banned substances.<ref name=hobson />

== Metabolism == β-Alanine can undergo a transamination reaction with pyruvate to form malonate-semialdehyde and L-alanine. The malonate semialdehyde can then be converted into malonate via malonate-semialdehyde dehydrogenase. Malonate is then converted into malonyl-CoA and enter fatty acid biosynthesis.<ref name=":0">{{Cite web|url=http://www.genome.jp/kegg-bin/show_pathway?scale=1.0&query=1.2.1.15&map=map00410&scale=&auto_image=&show_description=hide&multi_query=|title=KEGG PATHWAY: beta-Alanine metabolism - Reference pathway|website=www.genome.jp|access-date=2016-10-04}}</ref>

Alternatively, β-alanine can be diverted into pantothenic acid and coenzyme A biosynthesis.<ref name=":0" />

==References== {{reflist}}

==External links== * [http://www.genome.ad.jp/kegg/pathway/map/map00410.html KEGG map of β-alanine metabolism] {{Webarchive|url=https://web.archive.org/web/20090302170913/http://www.genome.ad.jp/kegg/pathway/map/map00410.html |date=2009-03-02 }}

{{DEFAULTSORT:Alanine, Beta-}} Category:Beta-Amino acids Category:Ergogenic aids Category:GABA reuptake inhibitors Category:Glycine receptor agonists Category:Non-proteinogenic amino acids Category:Inhibitory amino acids