Beta-alanine
Encyclopedia
β-Alanine is a naturally occurring beta amino acid, which are amino acids in which the amino group is at the β-position from the carboxylate group (i.e., two atoms away, see Figure 1). The IUPAC name for β-alanine would be 3-aminopropanoic acid. Unlike its normal counterpart, α-alanine
, β-alanine has no chiral center.
β-Alanine is not used in the biosynthesis
of any major protein
s or enzyme
s. It is formed in vivo
by the degradation of dihydrouracil
and carnosine
. It is a component of the naturally occurring peptides carnosine and anserine
and also of pantothenic acid
(vitamin B5) which itself is a component of coenzyme A
. Under normal conditions, β-alanine is metabolized
into acetic acid
.
β-Alanine is the rate-limiting precursor of carnosine
, which is to say carnosine levels are limited by the amount of available β-alanine. 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.
Typically studies have used supplementing strategies of multiple doses of 400 mg or 800 mg, administered at regular intervals for up to eight hours, over periods ranging from 4 to 10 weeks. After a 10 week supplementing strategy, the reported increase in intramuscular carnosine content was an average of 80.1% (range 18 to 205%).
L-Histidine
, with a pKa of 6.1 is a relatively weak buffer over the physiological intramuscular pH range. However, when bound to other amino acids this increases nearer to 6.8-7.0. In particular, when bound to β-alanine the pKa value is 6.83, making this a very efficient intramuscular buffer. Furthermore, because of the position of the beta amino group, β-alanine dipeptides are not incorporated proteins and thus can be stored at relatively high concentrations (millimolar). 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.
β-Alanine, provided in solution or as powder in gelatine capsules, however, causes paraesthesia when ingested in amounts above 10 mg per kg body weight (bwt). This is variable between individuals. Symptoms may be experienced by some individuals as mild even at 10 mg per kg bwt, in a majority as significant at 20 mg per kg bwt, and severe at 40 mg per kg bwt. However, an equivalent amount (equimolar) to 40 mg per kg bwt, ingested in the form of histidine containing dipeptides in chicken broth extract, did not cause paraesthesia.
It is probable that the paraesthesia, a form of neuropathic pain, results from high peak blood-plasma concentrations of β-alanine since greater quantities, ingested in the form of the β-alanine / histidine (or methylhistidine) containing dipeptides (i.e. carnosine and anserine) in meat, do not cause the same symptoms. In this case the β-alanine absorption profile is flattened but sustained for a longer period of time, whereas, the β-alanine samples in the studies were administered as gelatine capsules containing powder. This resulted in plasma concentrations rising rapidly, peaking within 30 to 45 minutes, and being eliminated after 90 to 120 minutes. The paraesthesia caused is no indication of efficacy since the published studies undertaken so far have utilised doses of 400 mg or 800 mg at a time to avoid the paraesthesia. Furthermore, excretion of β-alanine in urine accounted for 0.60%(+/-0.09), 1.50%(+/-0.40) and 3.64%(+/-0.47) of the administered doses of 10, 20, or 40 mg per kg body weight, indicating greater losses occurring with increasing dosage.
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 receptor
s (GlyRs) (the agonist order: glycine >> β-alanine > taurine >> alanine, L-serine > proline).
A high potency artificial sweetener, called suosan
, is derived from beta-alanine.
Alanine
Alanine is an α-amino acid with the chemical formula CH3CHCOOH. The L-isomer is one of the 20 amino acids encoded by the genetic code. Its codons are GCU, GCC, GCA, and GCG. It is classified as a nonpolar amino acid...
, β-alanine has no chiral center.
β-Alanine is not used in the biosynthesis
Biosynthesis
Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
of any major protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s or enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s. It is formed in vivo
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
by the degradation of dihydrouracil
Dihydrouracil
Dihydrouracil is an intermediate in the catabolism of uracil.-See also:* Dihydrouracil dehydrogenase * Dihydrouracil oxidase* Dihydropyrimidinase...
and carnosine
Carnosine
Carnosine is a dipeptide of the amino acids beta-alanine and histidine. It is highly concentrated in muscle and brain tissues....
. It is a component of the naturally occurring peptides carnosine and anserine
Anserine
Anserine is a dipeptide found in the skeletal muscle and brain of mammals, and birds.It is an antioxidant and helps reduce fatigue....
and also of pantothenic acid
Pantothenic acid
Pantothenic acid, also called pantothenate or vitamin B5 , is a water-soluble vitamin. For many animals, pantothenic acid is an essential nutrient. Animals require pantothenic acid to synthesize coenzyme-A , as well as to synthesize and metabolize proteins, carbohydrates, and fats.Pantothenic acid...
(vitamin B5) which itself is a component of coenzyme A
Coenzyme A
Coenzyme A is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All sequenced genomes encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it as a substrate...
. Under normal conditions, β-alanine is metabolized
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
into acetic acid
Acetic acid
Acetic acid is an organic compound with the chemical formula CH3CO2H . It is a colourless liquid that when undiluted is also called glacial acetic acid. Acetic acid is the main component of vinegar , and has a distinctive sour taste and pungent smell...
.
β-Alanine is the rate-limiting precursor of carnosine
Carnosine
Carnosine is a dipeptide of the amino acids beta-alanine and histidine. It is highly concentrated in muscle and brain tissues....
, which is to say carnosine levels are limited by the amount of available β-alanine. 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.
Typically studies have used supplementing strategies of multiple doses of 400 mg or 800 mg, administered at regular intervals for up to eight hours, over periods ranging from 4 to 10 weeks. After a 10 week supplementing strategy, the reported increase in intramuscular carnosine content was an average of 80.1% (range 18 to 205%).
L-Histidine
Histidine
Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...
, with a pKa of 6.1 is a relatively weak buffer over the physiological intramuscular pH range. However, when bound to other amino acids this increases nearer to 6.8-7.0. In particular, when bound to β-alanine the pKa value is 6.83, making this a very efficient intramuscular buffer. Furthermore, because of the position of the beta amino group, β-alanine dipeptides are not incorporated proteins and thus can be stored at relatively high concentrations (millimolar). 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.
β-Alanine, provided in solution or as powder in gelatine capsules, however, causes paraesthesia when ingested in amounts above 10 mg per kg body weight (bwt). This is variable between individuals. Symptoms may be experienced by some individuals as mild even at 10 mg per kg bwt, in a majority as significant at 20 mg per kg bwt, and severe at 40 mg per kg bwt. However, an equivalent amount (equimolar) to 40 mg per kg bwt, ingested in the form of histidine containing dipeptides in chicken broth extract, did not cause paraesthesia.
It is probable that the paraesthesia, a form of neuropathic pain, results from high peak blood-plasma concentrations of β-alanine since greater quantities, ingested in the form of the β-alanine / histidine (or methylhistidine) containing dipeptides (i.e. carnosine and anserine) in meat, do not cause the same symptoms. In this case the β-alanine absorption profile is flattened but sustained for a longer period of time, whereas, the β-alanine samples in the studies were administered as gelatine capsules containing powder. This resulted in plasma concentrations rising rapidly, peaking within 30 to 45 minutes, and being eliminated after 90 to 120 minutes. The paraesthesia caused is no indication of efficacy since the published studies undertaken so far have utilised doses of 400 mg or 800 mg at a time to avoid the paraesthesia. Furthermore, excretion of β-alanine in urine accounted for 0.60%(+/-0.09), 1.50%(+/-0.40) and 3.64%(+/-0.47) of the administered doses of 10, 20, or 40 mg per kg body weight, indicating greater losses occurring with increasing dosage.
Even though much weaker than glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
(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
Strychnine
Strychnine is a highly toxic , colorless crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine causes muscular convulsions and eventually death through asphyxia or sheer exhaustion...
-sensitive inhibitory glycine receptor
Glycine receptor
The glycine receptor, or GlyR, is the receptor for the amino acid neurotransmitter glycine. GlyR is an ionotropic receptor that produces its effects through chloride current...
s (GlyRs) (the agonist order: glycine >> β-alanine > taurine >> alanine, L-serine > proline).
A high potency artificial sweetener, called suosan
Suosan
Suosan is calorie-free artificial sweetener derived from beta-Alanine.Suosan is a sodium salt of beta-4-nitroanilide aspartic acid and is 700 times sweeter than sucrose with a bitter aftertaste....
, is derived from beta-alanine.