β-Alanine

β-Alanine (beta-alanine) is a naturally occurring beta amino acid, which is an amino acid 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>Template:Cite journal</ref> It is produced industrially by the reaction of ammonia with β-propiolactone.<ref name=Ullmann>Template:Ullmann</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">Template:Cite web</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>Template:Cite journal</ref><ref name="Hill2007">Template:Cite journal</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 and β-alanine. Hence, by weight, only about 40% of the dose is available as β-alanine.<ref name="pharmacistanswers.com"/>

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>Template:Cite journal</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 pK_a of the imidazolium group is 6.83, which is ideal for buffering.<ref>Template:Cite journal</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. Template:Doi, 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>Template:Cite journal</ref>

Athletic performance enhancement

There is evidence that β-alanine supplementation can increase exercise and cognitive performance,<ref name=quesnale>Template:Cite journal</ref><ref name=hoffman>Template:Cite journal</ref><ref name=hobson>Template:Cite journal</ref><ref name="issn2015"/> for some sporting modalities,<ref>Template:Cite journal</ref> and exercises within a 0.5–10 min time frame.<ref>Template:Cite journal</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>Template:Cite journal</ref>

Ingestion of β-alanine can cause paraesthesia, reported as a tingling sensation, in a dose-dependent fashion.<ref name="issn2015">Template:Cite journal</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">Template:Cite web</ref>

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

External links

• KEGG map of β-alanine metabolism Template:Webarchive