Biofelsefe — Amino asitler
NFA 2020 / Aziz Yardımlı

 

SİTELER

Biofelsefe — Amino asitler


SİTE İÇİ ARAMA       
 
 
   
 

🛑 ANAHATLAR

 
   
Amino asidin genel yapısı
Bu yapı α-amino asitlerden biri (prolin, döngülü bir amino asit) dışında tümüne ortaktır. Karbona bağlı olan R grubu ya da yan zincir her bir amino asitte ayrıdır.

 
  • Amino asitler amin (-NH2) ve karboksil grup (-COOH) kapsayan ve bir R grubu (yan zincir) ile tamamlanan organik bileşimlerdir.
  • Glysin dışında tüm ortak amino asitler için, α-karbon dört ayrı gruba bağlıdır: bir karboxil grup, bir amino grubu, bir R grubu ve bir H atomu. (Glysinde R grubu bir başka H atomudur).
  • “Amino asit” terimi α-amino karboksilik asit için kısaltmadır.
  • Amino asitlerde kapsanan başlıca elementler C, H, O ve N’dir.
  • Doğal olarak oluşan 500 kadar amino asit vardır.
  • Genetik kodda yalnızca 20 amino asit bulunur.
  • Sınıflandırma: başlıca alfa- (α-), beta- (β-), gamma- (γ-) ya da delta- (δ-) amino asitler olarak yapılır (başka ölçütlere göre de sınıflandırmalar vardır).
  • Amino asitler bedende proteinler olarak sudan sonra ikinci büyük kütleyi oluşturur.
  • Amino asitler sinir iletiminde ve biosentezde de işlev görür.
  • Amino asitler peptit grupları oluşturarak proteinleri üretir.
  • 1808’de “asparagine” keşfedilen ilk amino asit oldu.
  • 20’nci amino asit 1935’te keşfedildi.
  • Peptit bağ bir amino asidin amino grubu ile bir başkasının karboksil grubu arasında oluşur.
  • Kısa polimer zincirlerine peptitler, uzun zincirlere polipeptitler ya da proteinler denir.
  • Bu zincirler lineer ya da dalsızdır.
  • The Amino Acid Sequences of Millions of Proteins Have Been Determined.
  • The Function of a Protein Depends on Its Amino Acid Sequence.

  • (Lehninger).

 



 
  Amino acid — CHEMICAL COMPOUND (B)

Amino acid — CHEMICAL COMPOUND (B)

Amino acid — CHEMICAL COMPOUND (B)

Introduction

Introduction

Introduction (B)


Amino acid
, any of a group of organic molecules that consist of a basic amino group (―NH2), an acidic carboxyl group (―COOH), and an organic R group (or side chain) that is unique to each amino acid. The term amino acid is short for α-amino [alpha-amino] carboxylic acid. Each molecule contains a central carbon (C) atom, called the α-carbon, to which both an amino and a carboxyl group are attached. The remaining two bonds of the α-carbon atom are generally satisfied by a hydrogen (H) atom and the R group. The formula of a general amino acid is:

 
   
The amino acids differ from each other in the particular chemical structure of the R group.

 



 
Building Blocks Of Proteins

Building Blocks Of Proteins

Building Blocks Of Proteins (B)

Proteins are of primary importance to the continuing functioning of life on Earth. Proteins catalyze the vast majority of chemical reactions that occur in the cell. They provide many of the structural elements of a cell, and they help to bind cells together into tissues. Some proteins act as contractile elements to make movement possible. Others are responsible for the transport of vital materials from the outside of the cell (“extracellular”) to its inside (“intracellular”). Proteins, in the form of antibodies, protect animals from disease and, in the form of interferon, mount an intracellular attack against viruses that have eluded destruction by the antibodies and other immune system defenses. Many hormones are proteins. Last but certainly not least, proteins control the activity of genes (“gene expression”).

This plethora of vital tasks is reflected in the incredible spectrum of known proteins that vary markedly in their overall size, shape, and charge. By the end of the 19th century, scientists appreciated that, although there exist many different kinds of proteins in nature, all proteins upon their hydrolysis yield a class of simpler compounds, the building blocks of proteins, called amino acids. The simplest amino acid is called glycine, named for its sweet taste (glyco, “sugar”). It was one of the first amino acids to be identified, having been isolated from the protein gelatin in 1820. In the mid-1950s scientists involved in elucidating the relationship between proteins and genes agreed that 20 amino acids (called standard or common amino acids) were to be considered the essential building blocks of all proteins. The last of these to be discovered, threonine, had been identified in 1935.

 



 
Chirality

Chirality

Chirality (B)

All the amino acids but glycine are chiral molecules. That is, they exist in two optically active asymmetric forms (called enantiomers) that are the mirror images of each other. (This property is conceptually similar to the spatial relationship of the left hand to the right hand.) One enantiomer is designated D and the other L. It is important to note that the amino acids found in proteins almost always possess only the L-configuration. This reflects the fact that the enzymes responsible for protein synthesis have evolved to utilize only the L-enantiomers. Reflecting this near universality, the prefix L is usually omitted. Some D-amino acids are found in microorganisms, particularly in the cell walls of bacteria and in several of the antibiotics. However, these are not synthesized in the ribosome.

 



 
Acid-Base Properties

Acid-Base Properties

Acid-Base Properties (B)

Another important feature of free amino acids is the existence of both a basic and an acidic group at the α-carbon. Compounds such as amino acids that can act as either an acid or a base are called amphoteric. The basic amino group typically has a pKa between 9 and 10, while the acidic α-carboxyl group has a pKa that is usually close to 2 (a very low value for carboxyls). The pKa of a group is the pH value at which the concentration of the protonated group equals that of the unprotonated group. Thus, at physiological pH (about 7–7.4), the free amino acids exist largely as dipolar ions or “zwitterions” (German for “hybrid ions”; a zwitterion carries an equal number of positively and negatively charged groups). Any free amino acid and likewise any protein will, at some specific pH, exist in the form of a zwitterion. That is, all amino acids and all proteins, when subjected to changes in pH, pass through a state at which there is an equal number of positive and negative charges on the molecule. The pH at which this occurs is known as the isoelectric point (or isoelectric pH) and is denoted as pI. When dissolved in water, all amino acids and all proteins are present predominantly in their isoelectric form. Stated another way, there is a pH (the isoelectric point) at which the molecule has a net zero charge (equal number of positive and negative charges), but there is no pH at which the molecule has an absolute zero charge (complete absence of positive and negative charges). That is, amino acids and proteins are always in the form of ions; they always carry charged groups. This fact is vitally important in considering further the biochemistry of amino acids and proteins.

 



 
Standard Amino Acids

Standard Amino Acids

Standard Amino Acids (B)

One of the most useful manners by which to classify the standard (or common) amino acids is based on the polarity (that is, the distribution of electric charge) of the R group (e.g., side chain).

 



Group I: Nonpolar amino acids

Group I: Nonpolar amino acids (B)

Group I amino acids are glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, and tryptophan. The R groups of these amino acids have either aliphatic or aromatic groups. This makes them hydrophobic (“water fearing”). In aqueous solutions, globular proteins will fold into a three-dimensional shape to bury these hydrophobic side chains in the protein interior. The chemical structures of Group I amino acids are:

 
 
Isoleucine is an isomer of leucine, and it contains two chiral carbon atoms. Proline is unique among the standard amino acids in that it does not have both free α-amino and free α-carboxyl groups. Instead, its side chain forms a cyclic structure as the nitrogen atom of proline is linked to two carbon atoms. (Strictly speaking, this means that proline is not an amino acid but rather an α-imino acid.) Phenylalanine, as the name implies, consists of a phenyl group attached to alanine. Methionine is one of the two amino acids that possess a sulfur atom. Methionine plays a central role in protein biosynthesis ( translation) as it is almost always the initiating amino acid. Methionine also provides methyl groups for metabolism. Tryptophan contains an indole ring attached to the alanyl side chain.

 



Group II: Polar, uncharged amino acids

Group II: Polar, uncharged amino acids (B)

Group II: Polar, uncharged amino acids

Group II amino acids are serine, cysteine, threonine, tyrosine, asparagine, and glutamine. The side chains in this group possess a spectrum of functional groups. However, most have at least one atom (nitrogen, oxygen, or sulfur) with electron pairs available for hydrogen bonding to water and other molecules. The chemical structures of Group II amino acids are:

 
 
Two amino acids, serine and threonine, contain aliphatic hydroxyl groups (that is, an oxygen atom bonded to a hydrogen atom, represented as ―OH). Tyrosine possesses a hydroxyl group in the aromatic ring, making it a phenol derivative. The hydroxyl groups in these three amino acids are subject to an important type of posttranslational modification: phosphorylation (see below Nonstandard amino acids). Like methionine, cysteine contains a sulfur atom. Unlike methionine’s sulfur atom, however, cysteine’s sulfur is very chemically reactive (see below Cysteine oxidation). Asparagine, first isolated from asparagus, and glutamine both contain amide R groups. The carbonyl group can function as a hydrogen bond acceptor, and the amino group (NH2) can function as a hydrogen bond donor.

 



Group III: Acidic amino acids

Group III: Acidic amino acids (B)

The two amino acids in this group are aspartic acid and glutamic acid. Each has a carboxylic acid on its side chain that gives it acidic (proton-donating) properties. In an aqueous solution at physiological pH, all three functional groups on these amino acids will ionize, thus giving an overall charge of −1. In the ionic forms, the amino acids are called aspartate and glutamate. The chemical structures of Group III amino acids are

 
 
The side chains of aspartate and glutamate can form ionic bonds (“salt bridges”), and they can also function as hydrogen bond acceptors. Many proteins that bind metal ions (“metalloproteins”) for structural or functional purposes possess metal-binding sites containing aspartate or glutamate side chains or both. Free glutamate and glutamine play a central role in amino acid metabolism. Glutamate is the most abundant excitatory neurotransmitter in the central nervous system.

 



Group IV: Basic amino acids

Group IV: Basic amino acids (B)



The three amino acids in this group are arginine, histidine, and lysine. Each side chain is basic (i.e., can accept a proton). Lysine and arginine both exist with an overall charge of +1 at physiological pH. The guanidino group in arginine’s side chain is the most basic of all R groups (a fact reflected in its pKa value of 12.5). As mentioned above for aspartate and glutamate, the side chains of arginine and lysine also form ionic bonds. The chemical structures of Group IV amino acids are

 
 

The imidazole side chain of histidine allows it to function in both acid and base catalysis near physiological pH values. None of the other standard amino acids possesses this important chemical property. Therefore, histidine is an amino acid that most often makes up the active sites of protein enzymes.

The majority of amino acids in Groups II, III, and IV are hydrophilic (“water loving”). As a result, they are often found clustered on the surface of globular proteins in aqueous solutions.

 



 
Amino Acid Reactions

Amino Acid Reactions

Amino Acid Reactions (B)

Amino acids via their various chemical functionalities (carboxyls, amino, and R groups) can undergo numerous chemical reactions. However, two reactions (peptide bond and cysteine oxidation) are of particular importance because of their effect on protein structure.

 



Peptide bond

Peptide bond (B)

Amino acids can be linked by a condensation reaction in which an ―OH is lost from the carboxyl group of one amino acid along with a hydrogen from the amino group of a second, forming a molecule of water and leaving the two amino acids linked via an amide—called, in this case, a peptide bond. At the turn of the 20th century, German chemist Emil Fischer first proposed this linking together of amino acids. Note that when individual amino acids are combined to form proteins, their carboxyl and amino groups are no longer able to act as acids or bases, since they have reacted to form the peptide bond. Therefore, the acid-base properties of proteins are dependent upon the overall ionization characteristics of the individual R groups of the component amino acids.

 


The linking of atoms in a peptide bond..
 
Amino acids joined by a series of peptide bonds are said to constitute a peptide. After they are incorporated into a peptide, the individual amino acids are referred to as amino acid residues. Small polymers of amino acids (fewer than 50) are called oligopeptides, while larger ones (more than 50) are referred to as polypeptides. Hence, a protein molecule is a polypeptide chain composed of many amino acid residues, with each residue joined to the next by a peptide bond. The lengths for different proteins range from a few dozen to thousands of amino acids, and each protein contains different relative proportions of the 20 standard amino acids.
 


Condensation reaction in which three molecules of the amino acid glycine produce a tripeptide chain, with the elimination of two molecules of water (H2O).

 



Cysteine oxidation

Cysteine oxidation (B)

The thiol (sulfur-containing) group of cysteine is highly reactive. The most common reaction of this group is a reversible oxidation that forms a disulfide. Oxidation of two molecules of cysteine forms cystine, a molecule that contains a disulfide bond. When two cysteine residues in a protein form such a bond, it is referred to as a disulfide bridge. Disulfide bridges are a common mechanism used in nature to stabilize many proteins. Such disulfide bridges are often found among extracellular proteins that are secreted from cells. In eukaryotic organisms, formation of disulfide bridges occurs within the organelle called the endoplasmic reticulum.

In extracellular fluids (such as blood), the sulfhydryl groups of cysteine are rapidly oxidized to form cystine. In a genetic disorder known as cystinuria, there is a defect that results in excessive excretion of cystine into the urine. Because cystine is the least soluble of the amino acids, crystallization of the excreted cystine results in formation of calculi—more commonly known as “stones”—in the kidney, ureter, or urinary bladder. The stones may cause intense pain, infection, and blood in the urine. Medical intervention often involves the administration of D-penicillamine. Penicillamine works by forming a complex with cystine; this complex is 50 times more water-soluble than cystine alone.

In summary, it is the sequence of amino acids that determines the shape and biological function of a protein as well as its physical and chemical properties. Thus, the functional diversity of proteins arises because proteins are polymers of 20 different kinds of amino acids. For example, a “simple” protein is the hormone insulin, which has 51 amino acids. With 20 different amino acids to chose from at each of these 51 positions, a total of 2051, or about 1066, different proteins could theoretically be made.

 



 
Other Functions

Other Functions

Other Functions (B)

Amino acids are precursors of a variety of complex nitrogen-containing molecules. Prominent among these are the nitrogenous base components of nucleotides and the nucleic acids (DNA and RNA). Furthermore, there are complex amino-acid derived cofactors such as heme and chlorophyll. Heme is the iron-containing organic group required for the biological activity of vitally important proteins such as the oxygen-carrying hemoglobin and the electron-transporting cytochrome c. Chlorophyll is a pigment required for photosynthesis.

 


polynucleotide chain of deoxyribonucleic acid (DNA)
Portion of polynucleotide chain of deoxyribonucleic acid (DNA). The inset shows the corresponding pentose sugar and pyrimidine base in ribonucleic acid (RNA).
 

Several α-amino acids (or their derivatives) act as chemical messengers. For example, γ-aminobutyric acid (gamma-aminobutyric acid, or GABA; a derivative of glutamic acid), serotonin and melatonin (derivatives of tryptophan), and histamine (synthesized from histidine) are neurotransmitters. Thyroxine (a tyrosine derivative produced in the thyroid gland of animals) and indole acetic acid (a tryptophan derivative found in plants) are two examples of hormones.

Several standard and nonstandard amino acids often are vital metabolic intermediates. Important examples of this are the amino acids arginine, citrulline, and ornithine, which are all components of the urea cycle. The synthesis of urea is the principal mechanism for the removal of nitrogenous waste.

 



 
Nonstandard Amino Acids

Nonstandard Amino Acids

Nonstandard Amino Acids (B)

Nonstandard amino acids refer to those amino acids that have been chemically modified after they have been incorporated into a protein (called a “posttranslational modification”) and those amino acids that occur in living organisms but are not found in proteins. Among these modified amino acids is γ-carboxyglutamic acid, a calcium-binding amino acid residue found in the blood-clotting protein prothrombin (as well as in other proteins that bind calcium as part of their biological function). The most abundant protein by mass in vertebrates is collagen. Significant proportions of the amino acids in collagen are modified forms of proline and lysine: 4-hydroxyproline and 5-hydroxylysine.

 


Genes are made up of promoter regions and alternating regions of introns (noncoding sequences) and exons (coding sequences). The production of a functional protein involves the transcription of the gene from DNA into RNA, the removal of introns and splicing together of exons, the translation of the spliced RNA sequences into a chain of amino acids, and the posttranslational modification of the protein molecule.
 

Arguably, the most important posttranslational modification of amino acids in eukaryotic organisms (including humans) is the reversible addition of a phosphate molecule to the hydroxyl portion of the R groups of serine, threonine, and tyrosine. This event is known as phosphorylation and is used to regulate the activity of proteins in their minute-to-minute functioning in the cell. Serine is the most commonly phosphorylated residue in proteins, threonine is second, and tyrosine is third.

Proteins with carbohydrates (sugars) covalently attached to them are called glycoproteins. Glycoproteins are widely distributed in nature and provide the spectrum of functions already discussed for unmodified proteins. The sugar groups in glycoproteins are attached to amino acids through either oxygen (O-linked sugars) or nitrogen atoms (N-linked sugars) in the amino acid residues. The O-linked sugars are attached to proteins through the oxygen atoms in serine, threonine, hydroxylysine, or hydroxylproline residues. The N-linked sugars are attached to proteins through the nitrogen atom in asparagine.

Finally, there is the case of selenocysteine. Although it is part of only a few known proteins, there is a sound scientific reason to consider this the 21st amino acid because it is in fact introduced during protein biosynthesis rather than created by a posttranslational modification. Selenocysteine is actually derived from the amino acid serine (in a very complicated fashion), and it contains selenium instead of the sulfur of cysteine.

 



Analysis Of Amino Acid Mixtures

Analysis Of Amino Acid Mixtures (B)

The modern biochemist has a wide array of methods available for the separation and analysis of amino acids and proteins. These methods exploit the chemical differences of amino acids and in particular their ionization and solubility behaviour.

A typical determination of the amino acid composition of proteins involves three basic steps:

  1. Hydrolysis of the protein to its constituent amino acids.
  2. Separation of the amino acids in the mixture.
  3. Quantification of the individual amino acids.

 

Hydrolysis is accomplished by treatment of a purified protein with a concentrated acid solution (6N HCl) at a very high temperature (usually 110 °C [230 °F]) for up to 70 hours. These conditions cleave the peptide bond between each and every amino acid residue.

The hydrolyzed protein sample is then separated into its constituent amino acids. Methods important for amino acid separations include ion exchange chromatography, gas chromatography, high-performance liquid chromatography, and most recently, capillary zone electrophoresis.

The sensitivity of the analysis of separated amino acids has been greatly improved by the use of fluorescent molecules that are attached to the amino acids, followed by their subsequent detection using fluorescence spectroscopy. For example, amino acids may be chemically “tagged” with a small fluorescent molecule (such as o-phthalaldehyde). These approaches routinely allow as little as a picomole (10−12 mole) of an amino acid to be detected. Most recently, this range of sensitivity has been extended to the attomole (10−18 mole) range.

 



Some Common Uses

Some Common Uses (B)

The industrial production of amino acids is an important worldwide business. The first report of the commercial production of an amino acid was in 1908. It was then that the flavouring agent monosodium glutamate (MSG) was prepared from a type of large seaweed. This led to the commercial production of MSG, which is now produced using a bacterial fermentation process with starch and molasses as carbon sources. Glycine, cysteine, and D,L-alanine are also used as food additives, and mixtures of amino acids serve as flavour enhancers in the food industry. The amino acid balance of soy or corn protein for animal feed is significantly enhanced upon the addition of the nutritionally limiting amino acids methionine and lysine.

 


Monosodium glutamate (MSG)
Monosodium glutamate (MSG) crystals.
 

Amino acids are used therapeutically for nutritional and pharmaceutical purposes. For example, patients are often infused with amino acids to supply these nutrients before and after surgical procedures. Treatments with single amino acids are part of the medical approach to control certain disease states. Examples include L-dihydroxyphenylalanine (L-dopa) for Parkinson disease; glutamine and histidine to treat peptic ulcers; and arginine, citrulline, and ornithine to treat liver diseases.

Certain derivations of amino acids, especially of glutamate, are used as surfactants in mild soaps and shampoos. D-Phenylglycine and D-hydroxyphenylglycine are intermediates used for the chemical synthesis of β-lactam antibiotics (e.g., synthetic versions of penicillin). Aspartame is a sweetener prepared from the individual component amino acids aspartic acid and phenylalanine.

 



Amino Acids And The Origin Of Life On Earth

Amino Acids And The Origin Of Life On Earth (B)

The question of why organisms on Earth consist of L-amino acids instead of D-amino acids is still an unresolved riddle. Some scientists have long suggested that a substantial fraction of the organic compounds that were the precursors to amino acids—and perhaps some amino acids themselves—on early Earth may have been derived from comet and meteorite impacts. One such organic-rich meteorite impact occurred on September 28, 1969, over Murchison, Victoria, Australia. This meteorite is suspected to be of cometary origin because of its high water content of 12 percent. Dozens of different amino acids have been identified within the Murchison meteorite, some of which are found on Earth. Some compounds identified in the meteorite, however, have no apparent terrestrial source. Most intriguing are the reports that amino acids in the Murchison meteorite exhibit an excess of L-amino acids. An extraterrestrial source for an L-amino acid excess in the solar system could predate the origin of life on Earth and thus explain the presence of a similar excess of L-amino acids on the prelife Earth.

 



 







 
  Amino acid (W)

Amino acid

Amino acid (W)


The structure of an alpha amino acid in its un-ionized form.
 
   

Amino acids are organic compounds that contain amine (-NH2) and carboxyl (-COOH) functional groups, along with a side chain (R group) specific to each amino acid. The key elements of an amino acid are carbon (C), hydrogen (H), oxygen (O), and nitrogen (N), although other elements are found in the side chains of certain amino acids. About 500 naturally occurring amino acids are known (though only 20 appear in the genetic code) and can be classified in many ways. They can be classified according to the core structural functional groups' locations as alpha- (α-), beta- (β-), gamma- (γ-) or delta- (δ-) amino acids; other categories relate to polarity, pH level, and side chain group type (aliphatic, acyclic, aromatic, containing hydroxyl or sulfur, etc.).

In the form of proteins, amino acid residues form the second-largest component (water is the largest) of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis.

In biochemistry, amino acids having both the amine and the carboxylic acid groups attached to the first (alpha-) carbon atom have particular importance. They are known as 2-, alpha-, or α-amino acids (generic formula H2NCHRCOOH in most cases, where R is an organic substituent known as a "side chain"); often the term "amino acid" is used to refer specifically to these. They include the 22 proteinogenic (“protein-building”) amino acids, which combine into peptide chains ("polypeptides") to form the building-blocks of a vast array of proteins. These are all L-stereoisomers ("left-handed" isomers), although a few D-amino acids ("right-handed") occur in bacterial envelopes, as a neuromodulator (D-serine), and in some antibiotics.

Twenty of the proteinogenic amino acids are encoded directly by triplet codons in the genetic code and are known as "standard" amino acids. The other two ("non-standard" or "non-canonical") are selenocysteine (present in many prokaryotes as well as most eukaryotes, but not coded directly by DNA), and pyrrolysine (found only in some archaea and one bacterium). Pyrrolysine and selenocysteine are encoded via variant codons; for example, selenocysteine is encoded by stop codon and SECIS element. N-formylmethionine (which is often the initial amino acid of proteins in bacteria, mitochondria, and chloroplasts) is generally considered as a form of methionine rather than as a separate proteinogenic amino acid. Codon–tRNA combinations not found in nature can also be used to "expand" the genetic code and form novel proteins known as alloproteins incorporating non-proteinogenic amino acids.

Many important proteinogenic and non-proteinogenic amino acids have biological functions. For example, in the human brain, glutamate (standard glutamic acid) and gamma-amino-butyric acid ("GABA", non-standard gamma-amino acid) are, respectively, the main excitatory and inhibitory neurotransmitters. Hydroxyproline, a major component of the connective tissue collagen, is synthesised from proline. Glycine is a biosynthetic precursor to porphyrins used in red blood cells. Carnitine is used in lipid transport.

Nine proteinogenic amino acids are called “essential” for humans because they cannot be produced from other compounds by the human body and so must be taken in as food. Others may be conditionally essential for certain ages or medical conditions. Essential amino acids may also differ between species.

Because of their biological significance, amino acids are important in nutrition and are commonly used in nutritional supplements, fertilizers, feed, and food technology. Industrial uses include the production of drugs, biodegradable plastics, and chiral catalysts.

 
History

History

History (W)

The first few amino acids were discovered in the early 19th century. In 1806, French chemists Louis-Nicolas Vauquelin and Pierre Jean Robiquet isolated a compound in asparagus that was subsequently named asparagine, the first amino acid to be discovered. Cystine was discovered in 1810, although its monomer, cysteine, remained undiscovered until 1884. Glycine and leucine were discovered in 1820. The last of the 20 common amino acids to be discovered was threonine in 1935 by William Cumming Rose, who also determined the essential amino acids and established the minimum daily requirements of all amino acids for optimal growth.

The unity of the chemical category was recognized by Wurtz in 1865, but he gave no particular name to it. First use of the term "amino acid" in the English language dates from 1898, while the German term, Aminosäure, was used earlier. Proteins were found to yield amino acids after enzymatic digestion or acid hydrolysis. In 1902, Emil Fischer and Franz Hofmeister independently proposed that proteins are formed from many amino acids, whereby bonds are formed between the amino group of one amino acid with the carboxyl group of another, resulting in a linear structure that Fischer termed "peptide".

 



 
General structure

General structure

General structure (W)

In the structure shown at the top of the page, R represents a side chain specific to each amino acid. The carbon atom next to the carboxyl group (which is therefore numbered 2 in the carbon chain starting from that functional group) is called the α–carbon. Amino acids containing an amino group bonded directly to the alpha carbon are referred to as alpha amino acids. These include amino acids such as proline which contain secondary amines, which used to be often referred to as "imino acids".



The 21 proteinogenic α-amino acids found in eukaryotes, grouped according to their side chains' pKa values and charges carried at physiological pH (7.4)

 



Isomerism

Isomerism (W)

The alpha amino acids are the most common form found in nature, but only when occurring in the L-isomer. The alpha carbon is a chiral carbon atom, with the exception of glycine which has two indistinguishable hydrogen atoms on the alpha carbon. Therefore, all alpha amino acids but glycine can exist in either of two enantiomers, called L or D amino acids (relative configuration), which are mirror images of each other (see also Chirality). While L-amino acids represent all of the amino acids found in proteins during translation in the ribosome, D-amino acids are found in some proteins produced by enzyme posttranslational modifications after translation and translocation to the endoplasmic reticulum, as in exotic sea-dwelling organisms such as cone snails. They are also abundant components of the peptidoglycan cell walls of bacteria, and D-serine may act as a neurotransmitter in the brain. D-amino acids are used in racemic crystallography to create centrosymmetric crystals, which (depending on the protein) may allow for easier and more robust protein structure determination. The L and D convention for amino acid configuration refers not to the optical activity of the amino acid itself but rather to the optical activity of the isomer of glyceraldehyde from which that amino acid can, in theory, be synthesized (D-glyceraldehyde is dextrorotatory; L-glyceraldehyde is levorotatory). In alternative fashion, the (S) and (R) designators are used to indicate the absolute configuration. Almost all of the amino acids in proteins are (S) at the α carbon, with cysteine being (R) and glycine non-chiral. Cysteine has its side chain in the same geometric position as the other amino acids, but the R/S terminology is reversed because of the higher atomic number of sulfur compared to the carboxyl oxygen gives the side chain a higher priority by the Cahn–Ingold–Prelog rules, whereas the atoms in other side chains give them lower priority compared to the carboxyl group.

 



Side chains

Side chains (W)

Amino acids are designated as α- when the nitrogen atom is attached to the carbon atom adjacent to the carboxyl group: in this case the compound contains the sub-structure N-C-CO2. Amino acids with the sub-structure N-C-C-CO2 are classified as β- amino acids. γ- amino acids contain the sub-structure N-C-C-C-CO2, and so on.

Amino acids are usually classified by the properties of their side chain into four groups. The side chain can make an amino acid a weak acid or a weak base, and a hydrophile if the side chain is polar or a hydrophobe if it is nonpolar. The chemical structures of the 22 standard amino acids, along with their chemical properties, are described more fully in the article on these proteinogenic amino acids.

The phrase "branched-chain amino acids" or BCAA refers to the amino acids having aliphatic side chains that are linear; these are leucine, isoleucine, and valine. Proline is the only proteinogenic amino acid whose side-group links to the α-amino group and, thus, is also the only proteinogenic amino acid containing a secondary amine at this position. In chemical terms, proline is, therefore, an imino acid, since it lacks a primary amino group, although it is still classed as an amino acid in the current biochemical nomenclature, and may also be called an "N-alkylated alpha-amino acid".

 



Zwitterions

Zwitterions (W)

In aqueous solution amino acids exist in two forms (as illustrated at the right), the molecular form and the zwitterion form in equilibrium with each other. The two forms co-exist over the pH range pK1 - 2 to pK2 + 2, which for glycine is pH 0-12. The ratio of the concentrations of the two isomers is independent of pH. The value of this ratio cannot be determined experimentally.

Because all amino acids contain amine and carboxylic acid functional groups, they are amphiprotic. At pH = pK1 (ca. 2.2) there will be equal concentration of the species NH3+CH(R)CO2H and NH3+CH(R)CO2- and at pH = pK2 (ca. 10) there will be equal concentration of the species NH3+CH(R)CO2- and NH2CH(R)CO2-. It follows that the neutral molecule and the zwitterion are effectively the only species present at biological pH.

It is generally assumed that the concentration of the zwitterion is much greater than the concentration of the neutral molecule on the basis of comparisons with the known pK values of amines and carboxylic acids.



An amino acid in its (1) molecular and (2) zwitterionic forms.

 



Isoelectric point

Isoelectric point (W)

The variation in titration curves when the amino acids can be grouped by category. With the exception of tyrosine, using titration to distinguish among hydrophobic amino acids is problematic.

At pH values between the two pKa values, the zwitterion predominates, but coexists in dynamic equilibrium with small amounts of net negative and net positive ions. At the exact midpoint between the two pKa values, the trace amount of net negative and trace of net positive ions exactly balance, so that average net charge of all forms present is zero. This pH is known as the isoelectric point pI, so pI = ½(pKa1 + pKa2). The individual amino acids all have slightly different pKa values and therefore have different isoelectric points. For amino acids with charged side chains, the pKa of the side chain is involved. Thus for Asp or Glu with negative side chains, pI = ½(pKa1 + pKaR), where pKaR is the side chain pKa. Cysteine also has potentially negative side chain with pKaR = 8.14, so pI should be calculated as for Asp and Glu, even though the side chain is not significantly charged at physiological pH. For His, Lys, and Arg with positive side chains, pI = ½(pKaR + pKa2). Amino acids have zero mobility in electrophoresis at their isoelectric point, although this behaviour is more usually exploited for peptides and proteins than single amino acids. Zwitterions have minimum solubility at their isoelectric point, and some amino acids (in particular, with non-polar side chains) can be isolated by precipitation from water by adjusting the pH to the required isoelectric point.



Composite of titration curves of twenty proteinogenic amino acids grouped by side chain category.

 



 
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A polypeptide is an unbranched chain of amino acids.
 
 
Occurrence and functions in biochemistry

Proteinogenic amino acids

Proteinogenic amino acids (W)

Amino acids are the structural units (monomers) that make up proteins. They join together to form short polymer chains called peptides or longer chains called either polypeptides or proteins. These polymers are linear and unbranched, with each amino acid within the chain attached to two neighboring amino acids. The process of making proteins encoded by DNA/RNA genetic material is called translationand involves the step-by-step addition of amino acids to a growing protein chain by a ribozyme that is called a ribosome. The order in which the amino acids are added is read through the genetic code from an mRNA template, which is an RNA copy of one of the organism’s genes.

Twenty-two amino acids are naturally incorporated into polypeptides and are called proteinogenic or natural amino acids. Of these, 20 are encoded by the universal genetic code. The remaining 2, selenocysteine and pyrrolysine, are incorporated into proteins by unique synthetic mechanisms. Selenocysteine is incorporated when the mRNA being translated includes a SECIS element, which causes the UGA codon to encode selenocysteine instead of a stop codon. Pyrrolysine is used by some methanogenic archaea in enzymes that they use to produce methane. It is coded for with the codon UAG, which is normally a stop codon in other organisms. This UAG codon is followed by a PYLIS downstream sequence.

 


A polypeptide is an unbranched chain of amino acids.


The amino acid selenocysteine.

 



Non-proteinogenic amino acids

Non-proteinogenic amino acids (W)

Aside from the 22 proteinogenic amino acids, many non-proteinogenic amino acids are known. Those either are not found in proteins (for example carnitine, GABA, levothyroxine) or are not produced directly and in isolation by standard cellular machinery (for example, hydroxyproline and selenomethionine).

Non-proteinogenic amino acids that are found in proteins are formed by post-translational modification, which is modification after translation during protein synthesis. These modifications are often essential for the function or regulation of a protein. For example, the carboxylation of glutamate allows for better binding of calcium cations, and collagen contains hydroxyproline, generated by hydroxylation of proline. Another example is the formation of hypusine in the translation initiation factor EIF5A, through modification of a lysine residue. Such modifications can also determine the localization of the protein, e.g., the addition of long hydrophobic groups can cause a protein to bind to a phospholipid membrane.

Some non-proteinogenic amino acids are not found in proteins. Examples include 2-aminoisobutyric acid and the neurotransmitter gamma-aminobutyric acid. Non-proteinogenic amino acids often occur as intermediates in the metabolic pathways for standard amino acids – for example, ornithine and citrulline occur in the urea cycle, part of amino acid catabolism (see below). A rare exception to the dominance of α-amino acids in biology is the β-amino acid beta alanine (3-aminopropanoic acid), which is used in plants and microorganisms in the synthesis of pantothenic acid (vitamin B5), a component of coenzyme A.

 


β-alanine and its α-alanine isomer.

 



D-amino acid natural abundance

D-amino acid natural abundance (W)

Although D-isomers are uncommon in live organisms, gramicidin is a polypeptide made up from mixture of D- and L-amino acids. Other compounds containing D-amino acids are tyrocidine and valinomycin. These compounds disrupt bacterial cell walls, particularly in Gram-positive bacteria. As of 2011, only 837 D-amino acids were found in the Swiss-Prot database out of a total of 187 million amino acids analysed.

 



Non-standard amino acids

Non-standard amino acids (W)

The 20 amino acids that are encoded directly by the codons of the universal genetic code are called standard or canonical amino acids. A modified form of methionine (N-formylmethionine) is often incorporated in place of methionine as the initial amino acid of proteins in bacteria, mitochondria and chloroplasts. Other amino acids are called non-standard or non-canonical. Most of the non-standard amino acids are also non-proteinogenic (i.e. they cannot be incorporated into proteins during translation), but two of them are proteinogenic, as they can be incorporated translationally into proteins by exploiting information not encoded in the universal genetic code.

The two non-standard proteinogenic amino acids are selenocysteine (present in many non-eukaryotes as well as most eukaryotes, but not coded directly by DNA) and pyrrolysine (found only in some archaea and one bacterium). The incorporation of these non-standard amino acids is rare. For example, 25 human proteins include selenocysteine (Sec) in their primary structure, and the structurally characterized enzymes (selenoenzymes) employ Sec as the catalytic moiety in their active sites. Pyrrolysine and selenocysteine are encoded via variant codons. For example, selenocysteine is encoded by stop codon and SECIS element.

 



In human nutrition

In human nutrition (W)

When taken up into the human body from the diet, the 20 standard amino acids either are used to synthesize proteins, other biomolecules, or are oxidized to urea and carbon dioxide as a source of energy. The oxidation pathway starts with the removal of the amino group by a transaminase; the amino group is then fed into the urea cycle. The other product of transamidation is a keto acid that enters the citric acid cycle. Glucogenic amino acids can also be converted into glucose, through gluconeogenesis. Of the 20 standard amino acids, nine (His, Ile, Leu, Lys, Met, Phe, Thr, Trp and Val) are called essential amino acids because the human body cannot synthesize them from other compounds at the level needed for normal growth, so they must be obtained from food. In addition, cysteine, tyrosine, and arginine are considered semiessential amino acids, and taurine a semiessential aminosulfonic acid in children. The metabolic pathways that synthesize these monomers are not fully developed. The amounts required also depend on the age and health of the individual, so it is hard to make general statements about the dietary requirement for some amino acids. Dietary exposure to the non-standard amino acid BMAA has been linked to human neurodegenerative diseases, including ALS.

 



Non-protein functions

Non-protein functions (W)

In humans, non-protein amino acids also have important roles as metabolic intermediates, such as in the biosynthesis of the neurotransmitter gamma-amino-butyric acid (GABA). Many amino acids are used to synthesize other molecules, for example:

 

Some non-standard amino acids are used as defenses against herbivores in plants. For example, canavanine is an analogue of arginine that is found in many legumes, and in particularly large amounts in Canavalia gladiata (sword bean). This amino acid protects the plants from predators such as insects and can cause illness in people if some types of legumes are eaten without processing. The non-protein amino acid mimosine is found in other species of legume, in particular Leucaena leucocephala. This compound is an analogue of tyrosine and can poison animals that graze on these plants.

 



 
Synthesis

Chemical synthesis

Chemical synthesis (W)

Main article: Amino acid synthesis

The commercial production of amino acids usually relies on mutant bacteria that overproduce individual amino acids using glucose as a carbon source. Some amino acids are produced by enzymatic conversions of synthetic intermediates. 2-Aminothiazoline-4-carboxylic acid is an intermediate in one industrial synthesis of L-cysteine for example. Aspartic acid is produced by the addition of ammonia to fumarate using a lyase.

 

The Strecker amino acid synthesis.

 



Biosynthesis

Biosynthesis (W)

In plants, nitrogen is first assimilated into organic compounds in the form of glutamate, formed from alpha-ketoglutarate and ammonia in the mitochondrion. For other amino acids, plants use transaminases to move the amino group from glutamate to another alpha-keto acids. For example, aspartate aminotransferase converts glutamate and oxaloacetate to alpha-ketoglutarate and aspartate. Other organisms use transaminases for amino acid synthesis, too.

Nonstandard amino acids are usually formed through modifications to standard amino acids. For example, homocysteine is formed through the transsulfuration pathway or by the demethylation of methionine via the intermediate metabolite S-adenosyl methionine, while hydroxyproline is made by a posttranslational modification of proline.

Microorganisms and plants synthesize many uncommon amino acids. For example, some microbes make 2-aminoisobutyric acid and lanthionine, which is a sulfide-bridged derivative of alanine. Both of these amino acids are found in peptidic lantibiotics such as alamethicin. However, in plants, 1-aminocyclopropane-1-carboxylic acid is a small disubstituted cyclic amino acid that is a key intermediate in the production of the plant hormone ethylene.

 



 
Reactions

Reactions

Reactions (W)

Amino acids undergo the reactions expected of the constituent functional groups. The types of these reactions are determined by the groups on these side chains and are, therefore, different between the various types of amino acid.

 



Peptide bond formation

Peptide bond formation (W)

As both the amine and carboxylic acid groups of amino acids can react to form amide bonds, one amino acid molecule can react with another and become joined through an amide linkage. This polymerization of amino acids is what creates proteins. This condensation reaction yields the newly formed peptide bond and a molecule of water. In cells, this reaction does not occur directly; instead, the amino acid is first activated by attachment to a transfer RNA molecule through an ester bond. This aminoacyl-tRNA is produced in an ATP-dependent reaction carried out by an aminoacyl tRNA synthetase. This aminoacyl-tRNA is then a substrate for the ribosome, which catalyzes the attack of the amino group of the elongating protein chain on the ester bond. As a result of this mechanism, all proteins made by ribosomes are synthesized starting at their N-terminus and moving toward their C-terminus.

However, not all peptide bonds are formed in this way. In a few cases, peptides are synthesized by specific enzymes. For example, the tripeptide glutathione is an essential part of the defenses of cells against oxidative stress. This peptide is synthesized in two steps from free amino acids. In the first step, gamma-glutamylcysteine synthetase condenses cysteine and glutamic acid through a peptide bond formed between the side chain carboxyl of the glutamate (the gamma carbon of this side chain) and the amino group of the cysteine. This dipeptide is then condensed with glycine by glutathione synthetase to form glutathione.

In chemistry, peptides are synthesized by a variety of reactions. One of the most-used in solid-phase peptide synthesis uses the aromatic oxime derivatives of amino acids as activated units. These are added in sequence onto the growing peptide chain, which is attached to a solid resin support. The ability to easily synthesize vast numbers of different peptides by varying the types and order of amino acids (using combinatorial chemistry) has made peptide synthesis particularly important in creating libraries of peptides for use in drug discovery through high-throughput screening.

The combination of functional groups allow amino acids to be effective polydentate ligands for metal-amino acid chelates. The multiple side chains of amino acids can also undergo chemical reactions.

 


The condensation of two amino acids to form a dipeptide through a peptide bond.

 



Catabolism

Catabolism (W)

Amino acids must first pass out of organelles and cells into blood circulation via amino acid transporters, since the amine and carboxylic acid groups are typically ionized. Degradation of an amino acid, occurring in the liver and kidneys, often involves deamination by moving its amino group to alpha-ketoglutarate, forming glutamate. This process involves transaminases, often the same as those used in amination during synthesis. In many vertebrates, the amino group is then removed through the urea cycle and is excreted in the form of urea. However, amino acid degradation can produce uric acid or ammonia instead. For example, serine dehydratase converts serine to pyruvate and ammonia. After removal of one or more amino groups, the remainder of the molecule can sometimes be used to synthesize new amino acids, or it can be used for energy by entering glycolysis or the citric acid cycle, as detailed in image at right.

 


Catabolism of proteinogenic amino acids. Amino acids can be classified according to the properties of their main products as either of the following: * Glucogenic, with the products having the ability to form glucose by gluconeogenesis * Ketogenic, with the products not having the ability to form glucose. These products may still be used for ketogenesis or lipid synthesis. * Amino acids catabolized into both glucogenic and ketogenic products..

 



Complexation

Complexation (W)

Amino acids are bidentate ligands, forming transition metal amino acid complexes.

 

 



 







 
 

 


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