Alanine
Encyclopedia
Alanine is an α-amino acid
with the chemical formula
CH3CH(NH2)COOH. The L-isomer is one of the 20 amino acid
s encoded by the genetic code
. Its codons are GCU, GCC, GCA, and GCG. It is classified as a nonpolar amino acid. L-Alanine is second only to leucine
in rate of occurrence, accounting for 7.8% of the primary structure
in a sample of 1,150 proteins. D-Alanine occurs in bacterial cell walls and in some peptide antibiotics.
atom of alanine is bound with a methyl group (-CH3), making it one of the simplest α-amino acids with respect to molecular structure and also resulting in alanine's being classified as an aliphatic
amino acid. The methyl group of alanine is non-reactive and is thus almost never directly involved in protein function.
, meaning it can be manufactured by the human body, and does not need to be obtained directly through the diet. Alanine is found in a wide variety of foods, but is particularly concentrated in meats.
Good sources of alanine include
such as valine
, leucine
, and isoleucine
.
Alanine is most commonly produced by reductive amination
of pyruvate. Because transamination
reactions are readily reversible and pyruvate pervasive, alanine can be easily formed and thus has close links to metabolic pathways such as glycolysis
, gluconeogenesis
, and the citric acid cycle
. It also arises together with lactate and generates glucose from protein via the alanine cycle
.
alanine can be prepared by the condensation of acetaldehyde
with ammonium chloride
in the presence of sodium cyanide
by the Strecker reaction
, or by the ammonolysis of 2-bromopropanoic acid:
by transamination
. Glutamate can then transfer its amino group through the action of alanine aminotransferase to pyruvate, a product of muscle glycolysis
, forming alanine and α-ketoglutarate. The alanine formed is passed into the blood and transported to the liver. A reverse of the alanine aminotransferase reaction takes place in liver. Pyruvate regenerated forms glucose through gluconeogenesis
, which returns to muscle through the circulation system. Glutamate in the liver enters mitochondria and degrades into ammonium ion through the action of glutamate dehydrogenase
, which in turn participate in the urea cycle
to form urea
.
The glucose–alanine cycle enables pyruvate and glutamate to be removed from the muscle and find their way to the liver. Glucose is regenerated from pyruvate and then returned to muscle: the energetic burden of gluconeogenesis is thus imposed on the liver instead of the muscle. All available ATP
in muscle is devoted to muscle contraction.
found a correlation between high levels of alanine and higher blood pressure, energy intake, cholesterol levels, and body mass index.
of an alanine molecule produces a stable alkyl free radical
, CH3C•HCOO–. Deamination can be induced in solid or aqueous alanine by radiation.
This property of alanine is used in dosimetric measurements
in radiotherapy. When normal alanine is irradiated, the radiation causes certain alanine molecules to become free radicals, and, as these radicals are stable, the free radical content can later be measured in order to find out how much radiation the alanine was exposed to. In this way, one can be assured that complex radiotherapy treatment plans will deliver the intended pattern of radiation dose.
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
with the chemical formula
Chemical formula
A chemical formula or molecular formula is a way of expressing information about the atoms that constitute a particular chemical compound....
CH3CH(NH2)COOH. The L-isomer is one of the 20 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s encoded by the genetic code
Genetic code
The genetic code is the set of rules by which information encoded in genetic material is translated into proteins by living cells....
. Its codons are GCU, GCC, GCA, and GCG. It is classified as a nonpolar amino acid. L-Alanine is second only to leucine
Leucine
Leucine is a branched-chain α-amino acid with the chemical formula HO2CCHCH2CH2. Leucine is classified as a hydrophobic amino acid due to its aliphatic isobutyl side chain. It is encoded by six codons and is a major component of the subunits in ferritin, astacin and other 'buffer' proteins...
in rate of occurrence, accounting for 7.8% of the primary structure
Primary structure
The primary structure of peptides and proteins refers to the linear sequence of its amino acid structural units. The term "primary structure" was first coined by Linderstrøm-Lang in 1951...
in a sample of 1,150 proteins. D-Alanine occurs in bacterial cell walls and in some peptide antibiotics.
Structure
The α-carbonAlpha carbon
The alpha carbon in organic chemistry refers to the first carbon that attaches to a functional group . By extension, the second carbon is the beta carbon, and so on....
atom of alanine is bound with a methyl group (-CH3), making it one of the simplest α-amino acids with respect to molecular structure and also resulting in alanine's being classified as an aliphatic
Aliphatic compound
In organic chemistry, aliphatic compounds are acyclic or cyclic, non-aromatic carbon compounds.Thus, aliphatic compounds are opposite to aromatic compounds.- Structure :...
amino acid. The methyl group of alanine is non-reactive and is thus almost never directly involved in protein function.
Dietary sources
Alanine is a nonessential amino acidEssential amino acid
An essential amino acid or indispensable amino acid is an amino acid that cannot be synthesized de novo by the organism , and therefore must be supplied in the diet.-Essentiality vs. conditional essentiality in humans:...
, meaning it can be manufactured by the human body, and does not need to be obtained directly through the diet. Alanine is found in a wide variety of foods, but is particularly concentrated in meats.
Good sources of alanine include
- Animal sources: meat, seafood, caseinate, dairy products, eggs, fish, gelatin, lactalbumin
- Vegetarian sources: beans, nuts, seeds, soy, whey, brewer's yeast, brown rice, bran, corn, legumes, whole grains.
Biosynthesis
Alanine can be manufactured in the body from pyruvate and branched chain amino acidsBranched-chain amino acids
A branched-chain amino acid is an amino acid having aliphatic side-chains with a branch...
such as valine
Valine
Valine is an α-amino acid with the chemical formula HO2CCHCH2. L-Valine is one of 20 proteinogenic amino acids. Its codons are GUU, GUC, GUA, and GUG. This essential amino acid is classified as nonpolar...
, leucine
Leucine
Leucine is a branched-chain α-amino acid with the chemical formula HO2CCHCH2CH2. Leucine is classified as a hydrophobic amino acid due to its aliphatic isobutyl side chain. It is encoded by six codons and is a major component of the subunits in ferritin, astacin and other 'buffer' proteins...
, and isoleucine
Isoleucine
Isoleucine is an α-amino acid with the chemical formula HO2CCHCHCH2CH3. It is an essential amino acid, which means that humans cannot synthesize it, so it must be ingested. Its codons are AUU, AUC and AUA....
.
Alanine is most commonly produced by reductive amination
Reductive amination
Reductive amination is a form of amination that involves the conversion of a carbonyl group to an amine via an intermediate imine...
of pyruvate. Because transamination
Transamination
There are two chemical reactions known as transamination . The first is the reaction between an amino acid and an alpha-keto acid...
reactions are readily reversible and pyruvate pervasive, alanine can be easily formed and thus has close links to metabolic pathways such as glycolysis
Glycolysis
Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...
, gluconeogenesis
Gluconeogenesis
Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....
, and the citric acid cycle
Citric acid cycle
The citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...
. It also arises together with lactate and generates glucose from protein via the alanine cycle
Alanine cycle
The alanine cycle is quite similar to the Cori cycle. When muscles produce lactate during times of decreased oxygen, they also produce alanine. This alanine is shuttled to the liver where it is used to make glucose....
.
Chemical synthesis
RacemicRacemic
In chemistry, a racemic mixture, or racemate , is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was "racemic acid", which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.- Nomenclature :A...
alanine can be prepared by the condensation of acetaldehyde
Acetaldehyde
Acetaldehyde is an organic chemical compound with the formula CH3CHO or MeCHO. It is one of the most important aldehydes, occurring widely in nature and being produced on a large scale industrially. Acetaldehyde occurs naturally in coffee, bread, and ripe fruit, and is produced by plants as part...
with ammonium chloride
Ammonium chloride
Ammonium chloride NH4Cl is an inorganic compound with the formula NH4Cl. It is a white crystalline salt that is highly soluble in water. Solutions of ammonium chloride are mildly acidic. Sal ammoniac is a name of natural, mineralogical form of ammonium chloride...
in the presence of sodium cyanide
Sodium cyanide
Sodium cyanide is an inorganic compound with the formula NaCN. This highly toxic colorless salt is used mainly in gold mining but has other niche applications...
by the Strecker reaction
Strecker amino acid synthesis
The Strecker amino acid synthesis, devised by Adolph Strecker, is a series of chemical reactions that synthesize an amino acid from an aldehyde . The aldehyde is condensed with ammonium chloride in the presence of potassium cyanide to form an α-aminonitrile, which is subsequently hydrolyzed to give...
, or by the ammonolysis of 2-bromopropanoic acid:
Glucose–alanine cycle
Alanine plays a key role in glucose–alanine cycle between tissues and liver. In muscle and other tissues that degrade amino acids for fuel, amino groups are collected in the form of glutamateGlutamic acid
Glutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...
by transamination
Transamination
There are two chemical reactions known as transamination . The first is the reaction between an amino acid and an alpha-keto acid...
. Glutamate can then transfer its amino group through the action of alanine aminotransferase to pyruvate, a product of muscle glycolysis
Glycolysis
Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...
, forming alanine and α-ketoglutarate. The alanine formed is passed into the blood and transported to the liver. A reverse of the alanine aminotransferase reaction takes place in liver. Pyruvate regenerated forms glucose through gluconeogenesis
Gluconeogenesis
Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....
, which returns to muscle through the circulation system. Glutamate in the liver enters mitochondria and degrades into ammonium ion through the action of glutamate dehydrogenase
Glutamate dehydrogenase
Glutamate dehydrogenase is an enzyme, present in most microbes and the mitochondria of eukaryotes, as are some of the other enzymes required for urea synthesis, that converts glutamate to α-Ketoglutarate, and vice versa. In animals, the produced ammonia is, however, usually bled off to the urea...
, which in turn participate in the urea cycle
Urea cycle
The urea cycle is a cycle of biochemical reactions occurring in many animals that produces urea from ammonia . This cycle was the first metabolic cycle discovered , five years before the discovery of the TCA cycle...
to form urea
Urea
Urea or carbamide is an organic compound with the chemical formula CO2. The molecule has two —NH2 groups joined by a carbonyl functional group....
.
The glucose–alanine cycle enables pyruvate and glutamate to be removed from the muscle and find their way to the liver. Glucose is regenerated from pyruvate and then returned to muscle: the energetic burden of gluconeogenesis is thus imposed on the liver instead of the muscle. All available ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
in muscle is devoted to muscle contraction.
Link to hypertension
An international study led by Imperial College LondonImperial College London
Imperial College London is a public research university located in London, United Kingdom, specialising in science, engineering, business and medicine...
found a correlation between high levels of alanine and higher blood pressure, energy intake, cholesterol levels, and body mass index.
Link to Diabetes
Alterations in the alanine cycle that increase the levels of serum alanine aminotransferase (ALT) is linked to the development of diabetes. With an elevated level of ALT the risk of developing diabetes increases.Free radical stability
The deaminationDeamination
Deamination is the removal of an amine group from a molecule. Enzymes which catalyse this reaction are called deaminases.In the human body, deamination takes place primarily in the liver, however glutamate is also deaminated in the kidneys. Deamination is the process by which amino acids are...
of an alanine molecule produces a stable alkyl free radical
Radical (chemistry)
Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...
, CH3C•HCOO–. Deamination can be induced in solid or aqueous alanine by radiation.
This property of alanine is used in dosimetric measurements
Dosimetry
Radiation dosimetry is the measurement and calculation of the absorbed dose in matter and tissue resulting from the exposure to indirect and direct ionizing radiation...
in radiotherapy. When normal alanine is irradiated, the radiation causes certain alanine molecules to become free radicals, and, as these radicals are stable, the free radical content can later be measured in order to find out how much radiation the alanine was exposed to. In this way, one can be assured that complex radiotherapy treatment plans will deliver the intended pattern of radiation dose.