Amino acid

Amino acids ( unusual amino carboxylic acids outdated, amido acids ) are a class of organic compounds having at least one carboxyl group (-COOH) and an amino group (-NH2). The position of the amino group to the carboxyl group of the amino acids divides the class into groups. The most important amino acids have a terminal carboxyl group and in the immediate vicinity of the amino group. This is called vicinal or α -position; these amino acids belong to the α -amino acids as above.

The term amino acids is often simply used as a synonym for the proteinogenic amino acids. These α - Amino acids are the building blocks of proteins. So far, 23 proteinogenic amino acids known, the spectrum of the class of amino goes far beyond this. So 400 nonproteinogenic naturally occurring amino acids are previously known to have biological functions. The number of synthetically generated and the theoretically possible amino acids is significantly larger. Amino acids were also detected in comets and meteorites.

A special group represent the relatively rare D-amino acids

• 4.4.1 acid and base behavior
• Table 4.4.2 Summary of Properties
• 4.4.3 Stereochemistry

• 8.1 Books
• 8.2 journal articles

Extraction and production

Amino acids are obtained either from natural materials by separation of a hydrolyzed protein or synthetic means. Originally, the development of a synthesis of the various amino acids was mainly for structural elucidation. Meanwhile, these structural issues are resolved and the various syntheses, unless they are still up to date, the desired amino acids are specifically shown. In the syntheses initially created racemic mixtures which can be separated. A method for this is, for example, a selective enzymatic hydrolysis. For details, see separation process.

Below an overview of various syntheses that have been developed by chemists as early as the mid-19th century. Some of these older syntheses are due to low yields or other problems only of historical interest. However, these old methods have been partially developed and some are even today for the preparation of amino acids up to date. Further details of these syntheses including the equations for the syntheses are given below the links to the syntheses and the specified amino acids.

• With the cyanohydrin by Adolf Strecker '' alanine was first synthesized in 1850 from acetaldehyde.

• A synthesis for the preparation of glycine, on the α - acids, which are produced by the reaction of bromine or chlorine fatty acids with ammonia is sen WH Perkin. and Duppa already been developed in 1858.

• J. Pöchl discovered in 1883 the azlactone synthesis for the preparation of amino acids. Whose exact sequence but it was only in 1893 jun by Emil Erlenmeyer. elucidated. This method is therefore also called Erlenmeyer synthesis. With this method, histidine and phenylalanine in 1911 and thyroxine were prepared.

• By reduction of an α - oximino acid aspartic acid was first synthesized in 1887. The same method was presented in 1906 by L. Bouveault isoleucine from the oxime of methyl ethyl pyruvic acid ester.

• After developed by Siegmund Gabriel Gabriel synthesis, 1889 via glycine potassium phthalimide was synthesized as a starting chemical. Although this synthesis is obsolete for the representation of glycine, it is because of their high yields for the production of other amino acids.

• With the cyanohydrin synthesis presented Emil Fischer in 1902 for the first time on serine glycolaldehyde ago. 1906 was synthesized with his development of the malonic ester synthesis leucine. Isoleucine, norleucine, methionine, and phenylalanine are further amino acids, which are easily represented with this synthesis.

• Theodor Curtius used the Curtius degradation developed by him for the preparation of α -amino acids by the use of malonic ester derivatives for the synthesis of glycine, alanine, valine and phenylalanine.

• With a combined phthalimide - malonic ester synthesis was synthesized in 1931 by G. Barger methionine. By the same method and phenylalanine, proline, tyrosine, aspartic acid and serine may be prepared. V. Vigneaud you put 1939 DL -cystine ago using this method.

Amino acids are manufactured industrially by the following methods:

• Extraction Method: For this purpose, proteins are first hydrolyzed with acids. After precipitation of the amino acid from the hydrolyzate mixture, a separation is carried out by chromatography by means of ion exchangers, wherein in the elution, the different polarities of the amino acids are utilized.
• Chemical synthesis: There are a variety of synthetic methods. Examples are the Strecker synthesis of D, L -valine, Degussa - Synthesis of D, L- cysteine, and the synthesis of D, L- methionine methyl mercaptan, acrolein and hydrogen cyanide. As the amino acids are present as a racemate, then must be even method for enantiomer.
• Enzymatic method: This method has the advantage of providing enantiomerically pure L-or D -amino acids with appropriate enzymes as biocatalysts. Examples are the production of L- aspartic acid from fumaric acid, L- aspartase and the production of L- tryptophan from indole, pyruvic acid and with Tryptopharase.
• Fermentation method: The fermentation, the amino acids are produced with the aid of suitable microorganisms. The synthesis process takes place from highly complex intermediate steps within the cells. One example is the production of L- glutamic acid from glucose. Here you can win from 1 kg of glucose 0.5 kg glutamic acid.

General structure of amino acids

The unstable carbamic acid is not an amino acid, but a carboxamide. Strictly speaking, it is the mono-amide of carbonic acid. All the amino acids consist of at least two carbon atoms. Here, the carbon atom to which the amino group is, what are those class of amino acids chooses. Are represented more amino groups in the molecule, determined that of carbon, the amino group to the carboxyl carbon is closest to is which class of amino acids themselves.

• α -amino acids: the amino group of the α -amino acids is located at the second carbon atom, including the carboxy carbon atom. The counting always begins with the carboxyl carbon. Therefore, the IUPAC name is 2 -amino carboxylic acids. The simplest member of the α -amino acids is the proteinogenic amino acid glycine. The term amino acids is often used synonymously for a group of α -amino acids, mainly L- α - amino acids: the proteinogenic amino acids. The proteinogenic amino acids are the building blocks of all proteins of all life on Earth and in addition to the nucleic acids building blocks of life.
• β -amino acids: The amino group of the β -amino acids located at the third carbon atom ( the carboxyl carbon atom counted). The IUPAC name is 3 -amino carboxylic acids. The simplest example is β -alanine.
• γ -amino acids: the amino group of the γ -amino acids is located at the fourth carbon atom ( the carboxy carbon atom counted). The IUPAC name is 4 -amino carboxylic acids. The simplest example is γ -aminobutyric acid ( GABA).

The designation of other classes of amino acids results in the same way.

The amino acids of a class differ in their side chain R. If the side chain R different here from the other substituents are located at the carbon of the amino group, so there is a chiral center, and there are two enantiomers of the corresponding amino acid. Contains the side chain R even more stereocenters, the result is also diastereomers and the number of possible stereoisomers increases according to the number of additional stereocenters. Of amino acids with two differently substituted stereocenters, there are four stereoisomers.

Acid - base behavior, and

When solids and in neutral aqueous solutions are amino acids present as zwitterions, ie, the amino group is protonated and the carboxyl group is deprotonated. Generalizing the zwitterion can be represented as:

As a zwitterion, the protonated amino group as the acid ( proton donor ) and the carboxylate group can be used as base ( proton acceptor ) react. In acidic solutions, amino acids are present as cations and anions in basic solutions than before:

The charge of an amino acid molecule that is dependent on the pH of the solution. At a zwitterion is the total charge of the molecule is equal to zero. The corresponding pH is referred to as the isoelectric point ( PHI pI) of an amino acid. The solubility in water at the isoelectric point of an amino acid is the least.

Proteinogenic amino acids

As proteinogenic amino acids, all amino acids are referred to, which are the building blocks of proteins of living organisms. It always is in the proteinogenic amino acids to α -amino acids. Except for the amino acid glycine all proteinogenic amino acids are chiral: There are two enantiomers of each of these amino acids. Only one of the two enantiomers is proteinogenic and that the L-amino acid: the essential proteins for the construction of the apparatus - the ribosome, tRNA, the aminoacyl-tRNA synthetase ( this loading the tRNA with amino acids) and others - are themselves chiral and can only detect the L variant.

D-amino acids occur in living organisms are thinly scattered. You will then be but regardless of the proteinogenic metabolism synthesized and therefore remain nichtproteinogen. They are installed, for example, in the bacterial cell wall and bacterial short peptides as valinomycin (see carriers). One example is D -alanine.

Canonical amino acids

20 of the proteinogenic amino acids are encoded by codons of the genetic material. They are therefore referred to as the canonical amino acids or amino acids as a standard.

The canonical amino acid proline has, in contrast to the other canonical amino acids, is not a primary but a secondary amino group, and therefore also as a secondary amino acid, or incorrectly outdated often called imino acid, respectively.

In amino acid sequences of the amino acids are usually presented in single letter or three-letter code.

In addition to the codes listed above, there are placeholders that are used when it can not be concluded on the exact amino acid from the protein sequencing and X-ray structure analysis.

Noncanonical amino acids

Among the naturally occurring non-canonical amino acids include all other proteinogenic amino acids. These in turn can be divided into three classes:

• To the first class belong the amino acids that are incorporated by a recoding of the genetic material into proteins. The 21 and the 22 proteinogenic amino acid - selenocysteine ​​and pyrrolysine - belong to this class. It is believed that these amino acids probably do not have a canonical tRNA, but their tRNA derived from the canonical tRNAs (see selenocysteine ​​). The amino acids of this class are not used by all organisms.

• The second category contains the amino acids that arise from canonical amino acids, the amino acid residue R is changed after incorporation into proteins. For example, proline hydroxyproline, serine O- phosphoserine, O -phosphotyrosine to tyrosine and glutamate can be converted to γ - carboxyglutamate. An important modification of the amino acid residue represents the glycosylation: here the carbohydrate residues are transferred to the amino acid residues which arise glycoproteins.
• The third class includes the amino acids that can not be distinguished from the canonical amino acids of the organism, and which he therefore instead of incorporating non-specifically into proteins. This includes, for example, selenomethionine, which can be installed instead of the methionine, which canavanine, which can not be distinguished from the organism, or arginine azetidine-2- carboxylic acid, which acts as a proline analog. Many of the proteinogenic amino acids of this class are toxic because they often lead to misfolding of the protein, whereby the function of the protein may be impaired. So azetidine- 2-carboxylic acid is a toxic component of lily of the valley, with the lily of the valley protects with a highly specific prolyl -tRNA synthetase against the uncontrolled installation of this amino acid. Because of their often toxic effects of these amino acids are often not counted among the proteinogenic amino acids to which they belong, by definition.

Man himself uses the 20 canonical amino acids and selenocysteine ​​. Of the 20 canonical amino acids are synthesized by the human body 12 or by living in the human digestive tract microorganisms. The remaining 8 amino acids are essential for humans, that is, he must obtain them through diet.

The installation of artificial, almost any built amino acids on the replacement of the ligand in the corresponding tRNA synthetase is so far advanced that this target specific proteins can get a marker that after treatment with specific reagents for fluorescence stimulate the protein (example: installation of norbornene amino acid via Pyrrolysyl-tRNA-Synthetase/Codon CUA). Thus, an accurate localization of the protein is also possible without the production and reaction with antibodies.

Biochemical importance

Amino acids as building blocks of proteins

L-amino acids are of great importance in biochemistry because they are the building blocks of proteins and peptides ( proteins ). Generally, twenty proteinogenic amino acids are called in the literature called, that is, those that are encoded in the genome for proteins, however, are lately two more ( selenocysteine ​​and pyrrolysine ) added. In these, there always are α - amino acids because the amino group on the immediately adjacent carbon atom, which carries the functional carboxyl group ( Cα ) is bound. This 20 L-amino acids are encoded by three nucleobases in DNA. In addition, there are other amino acids which are constituents of proteins include, but are not be encoded.

Chains of amino acids are referred to depending on their length, the peptides or proteins. Amino acid chains having a length of less than about 100 amino acids are usually also referred to as peptides, until a greater chain length is referred to as proteins. The individual amino acids are linked within the chain of the so-called peptide bond ( amide ). An automated method for the synthesis of peptides provides the Merrifield synthesis.

In the form of food absorbed proteins are broken down during digestion into L -amino acids. In the liver they are recycled. Either they are used for protein synthesis or degraded (see also: Amino acid index). The main mechanisms of amino acid degradation are:

• Transamination
• Deamination
• Decarboxylation

Essential amino acids

Amino acids needed an animal organism, but can not produce itself, are called essential amino acids and must be obtained from the diet. All essential amino acids are L- α -amino acids. Human valine, methionine, leucine, isoleucine, phenylalanine, tryptophan, threonine and lysine are essential amino acids. Semi -essential amino acids must be taken only in certain situations with food, for example during growth or serious injury. The remaining amino acids are synthesized either directly or derived from other amino acids by modification. Cysteine ​​can be synthesized from the essential amino acid methionine. For children tyrosine is in addition to the generally essential amino acids essential because at this age the body function for its production of phenylalanine is not yet mature. There are also diseases that affect the metabolism of amino acids, then may need to actually non-essential amino acids are ingested with food yet. Chicken eggs, for example, contain all of the essential and semi- essential amino acids required by the human body.

Plants and microorganisms can synthesize all the amino acids necessary for themselves. Therefore there is no essential amino acids for them.

Physico-chemical properties

The proteinogenic amino acids can be prepared by their residues in groups split (see Table overview of the properties). It may appear an amino acid in different groups at the same time. In a Venn diagram, the overlapping of the groups can be represented graphically.

The properties of the side chain of cysteine ​​concerning the authors have different views: Loeffler it considers to be polar, while Alberts it considers to be non-polar. Proper way is with a sulfur heteroatom, thus applies: The side chain of cysteine ​​has weakly polar properties.

Acids and bases behavior

For the acid-base behavior of proteinogenic amino acids, especially the behavior of the side chain of the amino acid ( henceforth denoted with R ) interesting. Proteins in the NH2 and - COOH groups are at physiological pH ( around pH 7) because the peptide bond not protonated and are therefore not titratable. The exception of the amino and the carboxy -terminus of the protein. Is therefore essential for the acid-base behavior of proteins and peptides of the R group side chain.

The behavior of the side chain R depends on its constitution, that is, whether the side chain itself again can act as a proton acceptor or donator. The proteinogenous amino acids are classified according to functional groups in non-polar or polar amino acid side chains, and further sub-divided ( in the polarity sorted subsets ) in aliphatic, aromatic, amidated, sulfur -containing, hydroxylated, basic and acidic amino acids. The side chains of tyrosine and cysteine ​​are relatively acidic compared to the other non-polar side chains, but tend only at unphysiological high pH values ​​for deprotonation. Is a secondary amino acid proline as the N-terminus with the side chain includes a five-atom ring. Within a protein binds to the carboxy -terminus of the preceding amino acid on the nitrogen of the proline which is not protonated due to the aforementioned peptide bond. Histidine, tyrosine, and methionine are present in each two subsets.

Aliphatic amino acid side chains

• Alanine
• Glycine
• Isoleucine
• Leucine
• Methionine
• Proline
• Valine

Aromatic amino acid side chains

• Histidine
• Phenylalanine
• Tryptophan
• Tyrosine

Amidated amino acid side chains

• Asparagine
• Glutamine

Sulfur -containing amino acid side chains

• Cysteine
• Methionine

Hydroxylated amino acid side chains

• Serine
• Threonine
• Tyrosine

Basic amino acid side chains

• Lysine
• Arginine
• Histidine

Acidic amino acid side chains

• Aspartic acid (in water dissociates to aspartate )
• Glutamic acid (in water dissociates to glutamate )

The pK of the pH - value at which the titratable groups are protonated and deprotonated in equal parts. That is, the titratable group is equal parts in their basic, as in their acid form ( see also: Henderson -Hasselbalch equation).

It is usually the case, rather than to speak of the pKa on the pK, ie the pK of the acid. In this sense, however, should be by the pK of lysine as pK, are thus spoken of the pK of the base. For the sake of simplicity, this notation is but generally omitted since it also results from the context itself ( that is, whether the group acts as a base or acid).

The pK is not a constant but depends on the temperature, the activity, the ionic strength and the immediate environment of the titratable group and can therefore fluctuate.

If the pH is higher than the pK a titratable group, the titratable group is in its basic (deprotonated ) form. If the pH is lower than the pK a of the titratable group, the titratable group is in its acidic ( protonated ) form:

• Asp (pK = 3.86 ) at pH 7, the side chain is almost completely deprotonated
• Lys (pK = 10.53 ) at pH 7, the side chain is almost completely protonated

The side chains of basic amino acids are simply positively charged in their protonated (acidic) form and unloaded in their deprotonated ( basic ) form. The side chains of acidic amino acids (including cysteine ​​and tyrosine) are uncharged in their protonated (acidic) form and singly negatively charged in its deprotonated ( basic ) form. Therefore, the pH value for the properties of the side chain plays an important role, since the behavior of the side chain is a completely different if it is loaded or unloaded.

The titratable side chains affect, for example, the solubility of the corresponding amino acid. In polar solvents, the following applies: charged side chains make the amino acid soluble, uncharged side chains make the amino acid insoluble.

In proteins may lead to the fact that certain portions of hydrophilic or hydrophobic, whereby the folding, and thus the activity of enzymes is dependent on the pH. By strongly acidic or basic solutions proteins may therefore also be denatured.

Table summary of the properties

Stereochemistry

18 of the 20 proteinogenic amino acids have in accordance with the Cahn -Ingold-Prelog - Convention the α -carbon atom has the ( S) configuration, only cysteine ​​has the ( R)-configuration, since the carbon with the thiol group has a higher priority than the carboxylic acid group. Glycine is not chiral and therefore no absolute configuration can be determined.

In addition to the stereocenter at the α - carbon atom have isoleucine and threonine in their R each another stereogenic center. Proteinogenic isoleucine [R = -C * H (CH3) CH2CH3 ] there is (S)- configured, threonine, [R = -C * H (OH) CH 3 ] (R) configuration.

Nonproteinogenic amino acids

Of the non-proteinogenic, that is not occurring in proteins, amino acids are so far over 400 known which occur in organisms. This includes for example the L- thyroxin, thyroid hormone, L- DOPA, L- ornithine or almost all species of cyanobacteria proven neurotoxin β - Methylaminoalanin ( BMAA ). The L -azetidine -2 -carboxylic acid is a toxic component of the rhizomes of native lily of the valley (Convallaria majalis ) and sugar beet. It has an inhibitory effect on plant growth.

Most non-proteinogenic amino acids are derived from proteinogenic which are L- α -amino acids. Nevertheless, this result also β - amino acids ( β - alanine) or γ - amino acids ( GABA).

Among the non-proteinogenic amino acids include all D- enantiomers of proteinogenic L -amino acids. D-serine is generated ( its enantiomer ) in the brain through serine racemase from L- serine. It serves both as a neurotransmitter and as Gliotransmitter by the activation of the NMDA receptor, thus allowing the opening of the channel, along with glutamate. To open the ion channel glutamate and either glycine or D -serine must bind. D- serine at the glycine binding site of the glutamate receptor NMDA - type, a stronger agonist than glycine itself, but at the time of the first description of the glycine - binding site is still unknown. D-serine is D-aspartate by the second D- amino acid which is found in humans.

To synthetic amino acids include 2-amino -5- phosphonovaleriansäure (APV ), an antagonist of the NMDA receptor and the economically important D -phenylglycine [ Synonym: (R) -phenylglycine ], which as in the side chain of many semi- synthetic β - Lactamantibiotica is part of the structure contain. (S) - and (R) -tert- leucine ( Synonym: (S) - and (R) - β - methylvaline ) are synthetic structural isomers of the proteinogenic amino acid (S)- leucine and are used as starting material in the stereoselective syntheses.

There are also α - amino sulfonic acids [Example: 2- aminoethanesulfonic (synonym: Taurine ) ], α - amino phosphonic acids and α - amino phosphinic acids. Which are α -amino acids, but not α -amino carboxylic acids. Rather than a carboxyl group (-COOH), a sulfonic acid, phosphonic or phosphinic acid is present in those α -amino acids.

Use

Amino acids have a fundamental importance in the diet of man. In general, the supply of essential amino acids is completely covered by animal or a suitable combination of plant proteins (eg from cereals and legumes ). Plant proteins usually have a lower biological value. Feed in livestock in addition to amino acids, such as DL -methionine and L- lysine, enriched, so that their nutritional value is increased.

Amino acids or their derivatives are used as additives for food, especially as a flavor enhancer ( monosodium glutamate ), sweetener ( aspartame), and are precursors for certain flavorings, caused by the Maillard reaction in the food preparation.

In pharmacy or medicine L -amino acid infusion solutions for parenteral nutrition are applied. In addition, amino acids can also be used as excipients, for example as salt formers, buffers, and stabilizers in certain liver diseases. In diseases with a deficiency of neurotransmitters using L -dopa. Synthetic peptide hormones and the biosynthesis of antibiotics, amino acids are necessary starting materials. Magnesium and potassium aspartate play a role in the treatment of heart and circulatory diseases. Cysteine, or the derivatives acetylcysteine ​​and carbocysteine ​​, also provide an application in infectious bronchial diseases with increased bronchial secretions. In addition, L-cysteine ​​is used as the reducing agent in the permanent waving.

Amino acids are added in cosmetics skin care products and shampoos.