Amino acid

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This article is about the class of chemicals. For the structures and properties of the standard
proteinogenic amino acids, see Proteinogenic amino acid.

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

The 21 amino acids found in eukaryotes, grouped according to their side-chains' pKa values and
charges carried at physiological pH 7.4
Amino acids (/mino/, /mano/, or /mno/) are biologically important organic
compounds composed of amine (-NH2) and carboxylic acid (-COOH) functional groups, along
with a side-chain specific to each amino acid. The key elements of an amino acid are
carbon, hydrogen, oxygen, and nitrogen, though other elements are found in the sidechains of certain amino acids. About 500 amino acids are known[1] and can be classified in
many ways. They can be classified according to the core structural functional groups'
locations as alpha- (-), beta- (-), gamma- (-) or delta- (-) 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 acids
comprise the second-largest component (water is the largest) of human muscles, cells and
other tissues.[2] Outside proteins, amino acids perform critical roles in 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 amino acids (generic formula H2NCHRCOOH in most cases[3] where R is an organic substituent
known as a "side-chain");[4] often the term "amino acid" is used to refer specifically to these.
They incl,.ude the 23 proteinogenic ("protein-building") amino acids,[5][6][7] which combine into
peptide chains ("polypeptides") to form the building-blocks of a vast array of proteins.[8] These
are all L-stereoisomers ("left-handed" isomers), although a few D-amino acids ("right-handed")
occur in bacterial envelopes and some antibiotics.[9] 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 three ("non-standard" or "non-canonical") are selenocysteine (present in many
noneukaryotes as well as most eukaryotes, but not coded directly by DNA), pyrrolysine (found
only in some archea and one bacterium) and N-formylmethionine (which is often the initial
amino acid of proteins in bacteria, mitochondria, and chloroplasts). Pyrrolysine and
selenocysteine are encoded via variant codons; for example, selenocysteine is encoded by stop
codon and SECIS element.[10][11][12] CodontRNA combinations not found in nature can also be
used to "expand" the genetic code and create novel proteins known as alloproteins incorporating
non-proteinogenic amino acids.[13][14][15]
Many important proteinogenic and non-proteinogenic amino acids also play critical non-protein
roles within the body. 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;[16] hydroxyproline (a major component of the
connective tissue collagen) is synthesised from proline; the standard amino acid glycine is used
to synthesise porphyrins used in red blood cells; and the non-standard carnitine is used in lipid
transport.
Nine proteinogenic amino acids are called "essential" for humans because they cannot be created
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.[17]

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

Contents
[hide]

1 History

2 General structure
o 2.1 Isomerism
o 2.2 Zwitterions
o 2.3 Isoelectric point

3 Occurrence and functions in biochemistry

o 3.1 Essential amino acids
o 3.2 Non-proteinogenic amino acids
o 3.3 Non-standard amino acids
o 3.4 In human nutrition

4 Classification
o 4.1 Non-protein functions

5 Uses in industry
o 5.1 Expanded genetic code
o 5.2 Nullomers
o 5.3 Chemical building blocks
o 5.4 Biodegradable plastics

6 Reactions

o 6.1 Chemical synthesis

o 6.2 Peptide bond formation
o 6.3 Biosynthesis
o 6.4 Catabolism

7 Physicochemical properties of amino acids

o 7.1 Table of standard amino acid abbreviations and properties

8 See also

9 References and notes

10 Further reading

11 External links

History[edit]
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.[18][19] Cystine was
discovered in 1810,[20] although its monomer, cysteine, remained undiscovered until 1884.[19][21]
Glycine and leucine were discovered in 1820.[22] Usage of the term amino acid in the English
language is from 1898.[23] Proteins were found to yield amino acids after enzymatic digestion or
acid hydrolysis. In 1902, Emil Fischer and Franz Hofmeister proposed that proteins are the result
of the formation of bonds between the amino group of one amino acid with the carboxyl group of
another, in a linear structure that Fischer termed peptide.[24]

General structure[edit]
Further information: Proteinogenic amino acid

Lysine with the carbon atoms in the side-chain labeled

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 is called the carbon and amino acids with a
side-chain bonded to this carbon are referred to as alpha amino acids. These are the most
common form found in nature. In the alpha amino acids, the carbon is a chiral carbon atom,
with the exception of glycine.[25] In amino acids that have a carbon chain attached to the carbon
(such as lysine, shown to the right) the carbons are labeled in order as , , , , and so on.[26] In
some amino acids, the amine group is attached to the or -carbon, and these are therefore
referred to as beta or gamma amino acids.
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 sidechain is polar or a hydrophobe if it is nonpolar.[25] 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 non-linear; these are leucine, isoleucine, and valine. Proline is the only
proteinogenic amino acid whose side-group links to the -amino group and, thus, is also the only
proteinogenic amino acid containing a secondary amine at this position.[25] In chemical terms,
proline is, therefore, an imino acid, since it lacks a primary amino group,[27] although it is still
classed as an amino acid in the current biochemical nomenclature,[28] and may also be called an
"N-alkylated alpha-amino acid".[29]

The two enantiomers of alanine, D-alanine and L-alanine

Isomerism[edit]

Of the standard -amino acids, all but glycine can exist in either of two enantiomers, called L or
D amino acids, 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.[30] They are also abundant components of the peptidoglycan cell walls of
bacteria,[31] and D-serine may act as a neurotransmitter in the brain.[32] 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.[33] 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 stereochemistry. Almost all
of the amino acids in proteins are (S) at the carbon, with cysteine being (R) and glycine nonchiral.[34] Cysteine is unusual since it has a sulfur atom at the second position in its side-chain,
which has a larger atomic mass than the groups attached to the first carbon, which is attached to
the -carbon in the other standard amino acids, thus the (R) instead of (S).

An amino acid in its (1) un-ionized and (2) zwitterionic forms

Zwitterions[edit]
The amine and carboxylic acid functional groups found in amino acids allow them to have
amphiprotic properties.[25] Carboxylic acid groups (CO2H) can be deprotonated to become
negative carboxylates (CO2 ), and -amino groups (NH2) can be protonated to become
positive -ammonium groups (+NH3). At pH values greater than the pKa of the carboxylic acid
group (mean for the 20 common amino acids is about 2.2, see the table of amino acid structures
above), the negative carboxylate ion predominates. At pH values lower than the pKa of the ammonium group (mean for the 20 common -amino acids is about 9.4), the nitrogen is
predominantly protonated as a positively charged -ammonium group. Thus, at pH between 2.2
and 9.4, the predominant form adopted by -amino acids contains a negative carboxylate and a
positive -ammonium group, as shown in structure (2) on the right, so has net zero charge. This
molecular state is known as a zwitterion, from the German Zwitter meaning hermaphrodite or
hybrid.[35] Below pH 2.2, the predominant form will have a neutral carboxylic acid group and a
positive -ammonium ion (net charge +1), and above pH 9.4, a negative carboxylate and neutral
-amino group (net charge 1). The fully neutral form (structure (1) on the right) is a very minor
species in aqueous solution throughout the pH range (less than 1 part in 107). Amino acids exist

as zwitterions also in the solid phase, and crystallize with salt-like properties unlike typical
organic acids or amines.

Isoelectric point[edit]
The variation in titration curves when the amino acids are grouped by category can be seen here.
With the exception of tyrosine, using titration to differentiate between hydrophobic amino acids
is problematic.

Composite of Titration Curves Grouped by Side Chain Category using applet

http://cti.itc.virginia.edu/~cmg/Demo/compareAA/compareAAApplet.html
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.[36] This pH is known as the
isoelectric point pI, so pI = (pKa1 + pKa2). The individual amino acids all have slightly
different pKa values, so have different isoelectric points. For amino acids with charged sidechains, the pKa of the side-chain is involved. Thus for Asp, Glu with negative side-chains, pI =
(pKa1 + pKaR), where pKaR is the side-chain pKa. Cysteine also has potentially negative sidechain with pKaR = 8.14, so pI should be calculated as for Asp and Glu, even though the sidechain is not significantly charged at neutral pH. For His, Lys, and Arg with positive side-chains,
pI = (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.

Occurrence and functions in biochemistry[edit]

A polypeptide is an unbranched chain of amino acids.

Essential amino acids[edit]

Main article: Essential amino acids
See also: Protein primary structure and Posttranslational modification
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 is called translation and involves
the step-by-step addition of amino acids to a growing protein chain by a ribozyme that is called a
ribosome.[37] The order in which the amino acids are added is read through the genetic code from
an mRNA template, which is a RNA copy of one of the organism's genes.
Twenty-three amino acids are naturally incorporated into polypeptides and are called
proteinogenic or natural amino acids.[25] Of these, 21 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.[38] 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.[39] This UAG codon is followed by a PYLIS downstream sequence.[40]

The amino acid selenocysteine

Non-proteinogenic amino acids[edit]

Main article: Non-proteinogenic amino acids
Aside from the 23 proteinogenic amino acids, there are many other amino acids that are called
non-proteinogenic. Those either are not found in proteins (for example carnitine, GABA) 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,[41] and the hydroxylation
of proline is critical for maintaining connective tissues.[42] Another example is the formation of
hypusine in the translation initiation factor EIF5A, through modification of a lysine residue.[43]
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.[44]

-alanine and its -alanine isomer

Some non-proteinogenic amino acids are not found in proteins. Examples include lanthionine, 2aminoisobutyric acid, dehydroalanine, and the neurotransmitter gamma-aminobutyric acid. Nonproteinogenic 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).[45] A rare exception to the dominance of -amino acids in biology is the 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.[46]

Non-standard amino acids[edit]

The 20 amino acids that are encoded directly by the codons of the universal genetic code are
called standard or canonical amino acids. The others are called non-standard or non-canonical.
Most of the non-standard amino acids are also non-proteinogenic (i.e. they cannot be used to
build proteins), but three of them are proteinogenic, as they can be used to build proteins by
exploiting information not encoded in the universal genetic code.
The three non-standard proteinogenic amino acids are selenocysteine (present in many
noneukaryotes as well as most eukaryotes, but not coded directly by DNA), pyrrolysine (found
only in some archea and one bacterium), and N-formylmethionine (which is often the initial
amino acid of proteins in bacteria, mitochondria, and chloroplasts). For example, 25 human
proteins include selenocysteine (Sec) in their primary structure,[47] and the structurally
characterized enzymes (selenoenzymes) employ Sec as the catalytic moiety in their active sites.[48]
Pyrrolysine and selenocysteine are encoded via variant codons. For example, selenocysteine is
encoded by stop codon and SECIS element.[49][50][12]

In human nutrition[edit]
Further information: Protein in nutrition and Amino acid synthesis
When taken up into the human body from the diet, the 22 standard amino acids either are used to
synthesize proteins and other biomolecules or are oxidized to urea and carbon dioxide as a
source of energy.[51] 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.[52] Glucogenic amino acids can also
be converted into glucose, through gluconeogenesis.[53]
Pyrrolysine trait is restricted to several microbes, and only one organism has both Pyl and Sec.
Of the 22 standard amino acids, 9 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.[54] In addition, cysteine, taurine, tyrosine, and arginine are
considered semiessential amino-acids in children (though taurine is not technically an amino
acid), because the metabolic pathways that synthesize these amino acids are not fully developed.
[55][56]
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.

Essential
Histidine
Isoleucine
Leucine
Lysine
Methionine
Phenylalanine
Threonine
Tryptophan
Valine

Nonessential
Alanine
Arginine*
Asparagine
Aspartic acid
Cysteine*
Glutamic acid
Glutamine*
Glycine
Ornithine*
Proline*
Selenocysteine*
Serine*
Tyrosine*

(*) Essential only in certain cases.[57][58]

Classification[edit]
Although there are many ways to classify amino acids, these molecules can be assorted into six
main groups, on the basis of their structure and the general chemical characteristics of their R
groups.