Β-Alanine

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. It is produced industrially by the reaction of ammonia with β-propiolactone.

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. 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. 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.

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), 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 pKa of the imidazolium group is 6.83, which is ideal for buffering.

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).

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."

Athletic performance enhancement

There is evidence that β-alanine supplementation can increase exercise and cognitive performance, for some sporting modalities, and exercises within a 0.5–10 min time frame. 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.

Ingestion of β-alanine can cause paraesthesia, reported as a tingling sensation, in a dose-dependent fashion. 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. Furthermore, many studies have failed to test for the purity of the supplements used and check for the presence of banned substances.

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.

Alternatively, β-alanine can be diverted into pantothenic acid and coenzyme A biosynthesis.

References

References

1. {{Merck11th. 196.
2. {{RubberBible62nd
3. (2016). "CRC Handbook of Chemistry and Physics". [[CRC Press]].
4. (1969). "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 of the Chemical Society B: Physical Organic.
5. (2005). "Hydroxycarboxylic Acids, Aliphatic".
6. "Beta-Alanine Supplementation For Exercise Performance".
7. (August 9, 2007). "Beta-alanine supplementation augments muscle carnosine content and attenuates fatigue during repeated isokinetic contraction bouts in trained sprinters". J Appl Physiol.
8. (2007). "Influence of beta-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity". Amino Acids.
9. (1992). "Carnosine and anserine concentrations in the quadriceps femoris muscle of healthy humans". Eur. J. Appl. Physiol.
10. (1938). "The buffering of muscle in rigor: protein, phosphate and carnosine". Journal of Physiology.
11. ''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
12. (October 2010). "Beta-alanine as a small molecule neurotransmitter". Neurochem Int.
13. (2014). "The effects of beta-alanine supplementation on performance: a systematic review of the literature". Int J Sport Nutr Exerc Metab.
14. (2015). "β-Alanine supplementation and military performance". Amino Acids.
15. (9 December 2016). "Effects of β-alanine supplementation on exercise performance: a meta-analysis". Amino Acids.
16. (2019). "Ergogenic Effects of β-Alanine Supplementation on Different Sports Modalities: Strong Evidence or Only Incipient Findings?". [[The Journal of Strength and Conditioning Research]].
17. (2017). "β-alanine supplementation to improve exercise capacity and performance: a systematic review and meta-analysis FREE". British Journal of Sports Medicine.
18. (June 2010). "Role of beta-alanine supplementation on muscle carnosine and exercise performance". Med Sci Sports Exerc.
19. (2015). "International society of sports nutrition position stand: Beta-Alanine". J Int Soc Sports Nutr.
20. "KEGG PATHWAY: beta-Alanine metabolism - Reference pathway".