Amino acid
In chemistry, an amino acid is any molecule that contains both amino and carboxylic
acid functional groups. In biochemistry, this shorter and more general term is
frequently used to refer to alpha amino acids: those amino acids in which the amino
and carboxylate functionalities are attached to the same carbon.
Amino acid residue is what is left of an amino acid once a water molecule has been
lost (an H+ from the nitrogenous side and an OH- from the carboxylic side) in the
formation of a peptide bond .
Overview
Amino acids are the basic structural building units of proteins. They form short
polymer chains called peptides or polypeptides which in turn form structures called
proteins.
Twenty amino acids are encoded by the standard genetic code and are called
proteinogenic or standard amino acids. Rarer, more complicated ones are produced
by the body and are called nonstandard. Proline is the only proteinogenic amino acid
whose side group is cyclic and links to the a-amino group, forming a secondary amino
group. Formerly, proline was misleadingly called an imino acid. Other amino acids
contained in proteins are usually formed by post-translational modification, that is
modification after translation (protein synthesis). These modifications are often
essential for the function of the protein. At least two amino acids other than the
standard 20 are sometimes incorporated into proteins during translation:


Selenocysteine is incorporated into some proteins at a UGA codon, which is
normally a stop codon.
Pyrrolysine is used by some methanogens in enzymes that they use to produce
methane. It is coded for similarity to selenocysteine but with the codon UAG
instead.
Although only 20 amino acids are genetically coded, over 100 have been found in
nature. Some of these have been detected in meteorites, especially in a type known as
carbonaceous chondrites. Microorganisms and plants often produce very uncommon
amino acids, which can be found in peptidic antibiotics (e.g. nisin or alamethicin).
Lanthionine is a sulfide-bridged alanine dimer which is found together with
unsaturated amino acids in lantibiotics (antibiotic peptides of microbial origin). 1Aminocyclopropane-1-carboxylic acid (ACC) is a small disubstituted cyclic amino
acid and a key intermediate in the production of the plant hormone ethylene.
In addition to protein synthesis, amino acids have other biologically important roles.
Glycine, and glutamate, are used both as neurotransmitters and as standard amino
acids in proteins. Many amino acids are used to synthesize other molecules, such as
tryptophan which is a precursor of the neurotransmitter serotonin, and glycine which
is one of the reactants in the synthesis of porphyrins such as heme. Numerous nonstandard amino acids are also biologically important: GABA (another
neurotransmitter), carnitine (used in lipid transport within a cell), ornithine, citrulline,
homocysteine, hydroxyproline, hydroxylysine, and sarcosine.
Some of the 20 standard amino acids are called essential amino acids, because they
cannot be synthesized by the body from other compounds through chemical reactions,
but instead must be taken in with food. In humans, the essential amino acids are
lysine, leucine, isoleucine, methionine, phenylalanine, threonine, tryptophan, valine,
and (in children) histidine and arginine.
General structure
The general structure of proteinogenic alpha amino acids is:
COOH
|
H-C-R
|
NH2
Where "R" represents a side chain specific to each amino acid. Amino acids are
usually classified by properties of the side chain into four groups: acidic, basic,
hydrophilic (polar), and hydrophobic (nonpolar).
Isomerism
Except for glycine, where R = H, amino acids occur in two possible optical isomers,
called D and L. The L amino acids represent the vast majority of amino acids found in
proteins. D amino acids are found in some proteins produced by exotic sea-dwelling
organisms, such as cone snails. They are also abundant components of the cell walls
of bacteria.
Reactions
Proteins are created by polymerization of amino acids by peptide bonds in a process
called translation.
Peptide
bond
formation
1. Amino acid; 2, zwitterion structure; 3, two amino acids forming a peptide bond.
(See also bond.)
List of standard amino acids
Structures
Structures and symbols of the 20 amino acids present in genetic code.
Chemical properties
Following is a table listing the one letter symbols, the three letter symbols, and the
chemical properties of the side chains of the standard amino acids. The one letter
symbol for an undetermined amino acid is X. The three letter symbol Asx or one letter
symbol B means the amino acid is either asparagine or aspartic acid, while Glx or Z
means either glutamic acid or glutamine.
Abbrev. Full Name
Side
type
A Ala Alanine
hydrophobic 89.09
C Cys Cysteine
chain
Mass
hydrophobic
(Nagano,
121.16
1999)
pI
pK1
pK2
pKr
(α(α(R)
+
COOH) NH3)
6.11
2.35
9.87
5.05
1.92
10.70
8.37
D Asp Aspartic acid acidic
133.10
2.85
1.99
9.90
3.90
E Glu Glutamic acid acidic
147.13
3.15
2.10
9.47
4.07
Phe Phenylalanine hydrophobic 165.19
5.49
2.20
9.31
F
G Gly Glycine
hydrophobic 75.07
6.06
2.35
9.78
In even slightly
acidic
conditions
protonation of the
nitrogen
occurs,
changing
the
properties
of
histidine and the
polypeptide as a
whole. It is used by
many proteins as a
regulatory
mechanism,
changing
the
conformation
and
behavior of the
polypeptide in acidic
regions such as the
late endosome or
lysosome.
basic
155.16
7.60
1.80
9.33
I
hydrophobic 131.17
6.05
2.32
9.76
K Lys Lysine
basic
146.19
9.60
2.16
9.06
L Leu Leucine
hydrophobic 131.17
6.01
2.33
9.74
Isoleucine
Under
oxidizing
conditions,
two
cysteines can join
together
by
a
disulfide bond to
form the amino acid
cystine.
When
cysteines are part of
a protein, insulin for
example,
this
enforces
tertiary
structure.
Because of the two
hydrogen atoms at
the α carbon, glycine
is
not
optically
active.
H His Histidine
Ile
Remarks
6.04
10.54
M Met Methionine
hydrophobic 149.21
5.74
2.13
9.28
N Asn Asparagine
hydrophilic
5.41
2.14
8.72
P
Amino acid
Pro Proline
132.12
hydrophobic 115.13
6.30
1.95
10.64
Q Gln Glutamine
hydrophilic
146.15
5.65
2.17
9.13
R Arg Arginine
basic
174.20
10.76
1.82
8.99
S
hydrophilic
105.09
5.68
2.19
9.21
T Thr Threonine
hydrophilic
119.12
5.60
2.09
9.10
V Val Valine
hydrophobic 117.15
6.00
2.39
9.74
W Trp Tryptophan
hydrophobic 204.23
5.89
2.46
9.41
Y Tyr Tyrosine
hydrophobic 181.19
5.64
2.20
9.21
Ser
Serine
Hydrophobic Positive
Always the first
amino acid to be
incorporated into a
protein; sometimes
removed
after
translation.
Can disrupt protein
folding
structures
like α helix or β
sheet.
12.48
10.46
van
der
Negative Polar Charged Small Tiny Aromatic Aliphatic
Codon
Waals
volume
Occurrence
in proteins
(%)
Alanine
X
-
-
-
-
X
X
-
-
67
GCU,
GCC,
GCA,
GCG
Cysteine
X
-
-
-
-
X
-
-
-
86
UGU,
UGC
1.9
Aspartate
-
-
X
X
X
X
-
-
-
91
GAU,
GAC
5.3
Glutamate
-
-
X
X
X
-
-
-
-
109
GAA,
GAG
6.3
Phenylalanine
X
-
-
-
-
-
-
X
-
135
UUU,
UUC
3.9
7.2
7.8
Glycine
X
-
-
-
-
X
X
-
-
48
GGU,
GGC,
GGA,
GGG
Histidine
-
X
-
X
X
-
-
X
-
118
CAU,
CAC
2.3
Isoleucine
X
-
-
-
-
-
-
-
X
124
AUU,
AUC,
AUA
5.3
Lysine
-
X
-
X
X
-
-
-
-
135
AAA,
AAG
5.9
124
UUA,
UUG,
CUU,
CUC,
CUA,
CUG
9.1
Leucine
X
-
-
-
-
-
-
-
X
Methionine
Asparagine
Proline
Glutamine
Arginine
Serine
Threonine
X
-
X
-
-
-
X
-
-
-
X
-
-
-
-
-
-
-
-
X
-
X
X
X
X
-
-
-
X
-
-
X
X
-
-
X
X
-
-
-
-
X
-
-
-
-
-
-
-
-
-
-
-
-
-
124
AUG
2.3
96
AAU,
AAC
4.3
90
CCU,
CCC,
CCA,
CCG
5.2
114
GGU,
GGC,
GGA,
GGG
4.2
148
CGU,
CGC,
CGA,
CGG,
AGA,
AGG
5.1
73
UCU,
UCC,
UCA,
6.8
UCG,
AGU,AGC
93
ACU,
ACC,
ACA,
ACG
5.9
6.6
Valine
X
-
-
-
-
X
-
-
X
105
GUU,
GUC,
GUA,
GUG
Tryptophan
X
-
-
-
-
-
-
X
-
163
UGG
1.4
Tyrosine
X
-
-
X
-
-
-
X
-
141
UAU,
UAC
3.2
Nonstandard amino acids
Aside from the twenty standard amino acids, there is a vast number of nonstandard
amino acids not used in the body's regular manufacturing of proteins. Examples of
nonstandard amino acids include the sulfur-containing taurine and the
neurotransmitters GABA and dopamine.
Nonstandard amino acids are usually formed through modifications to standard amino
acids. For example, taurine can be formed by the decarboxylation of cysteine, while
dopamine is synthesized from tyrosine.
Uses of substances derived from amino acids



Monosodium glutamate is a food additive to enhance flavor.
L-DOPA (L-dihydroxyphenylalanine) is a drug used to treat Parkinsonism.
5-HTP (5-hydroxytryptophan) has been used to treat neurological problems
associated with PKU (phenylketonuria), as well as depression (as an
alternative to L-Tryptophan).
Protein
A representation of the 3D structure of myoglobin, showing coloured alpha helices.
This protein was the first to have its structure solved by X-ray crystallography by Max
Perutz and Sir John Cowdery Kendrew in 1958, which led to them receiving a Nobel
Prize in Chemistry.
A protein (in Greek πρωτεϊνη = first thread) is a complex, high-molecular-weight
organic compound that consists of amino acids joined by peptide bonds. Proteins are
essential to the structure and function of all living cells and viruses. Many proteins are
enzymes or subunits of enzymes. Other proteins play structural or mechanical roles,
such as those that form the struts and joints of the cytoskeleton, serving as biological
scaffolds for the mechanical integrity and tissue signalling functions. Still more
functions filled by proteins include immune response and the storage and transport of
various ligands. In nutrition, proteins serve as the source of amino acids for organisms
that do not synthesize those amino acids natively.
Proteins are one of the classes of bio-macromolecules, alongside polysaccharides,
lipids, and nucleic acids, that make up the primary constituents of living things. They
are among the most actively-studied molecules in biochemistry, and were discovered
by Jöns Jakob Berzelius in 1838.
Almost all natural proteins are encoded by DNA. DNA is transcribed to yield RNA,
which serves as a template for translation by ribosomes.
Structure
Proteins are amino acid chains that fold into unique 3-dimensional structures. The
shape into which a protein naturally folds is known as its native state, which is
determined by its sequence of amino acids. Biochemists refer to four distinct aspects
of a protein's structure:




Primary structure: the amino acid sequence
Secondary structure: highly patterned sub-structures—alpha helix and beta
sheet—or segments of chain that assume no stable shape. Secondary structures
are locally defined, meaning that there can be many different secondary motifs
present in one single protein molecule.
Tertiary structure: the overall shape of a single protein molecule; the spatial
relationship of the secondary structural motifs to one another
Quaternary structure: the shape or structure that results from the union of
more than one protein molecule, usually called subunit proteins subunits in
this context, which function as part of the larger assembly or protein complex.
In addition to these levels of structure, proteins may shift between several similar
structures in performing their biological function. In the context of these functional
rearrangements, these tertiary or quaternary structures are usually referred to as
"conformations," and transitions between them are called conformational changes.
The primary structure is held together by covalent peptide bonds, which are made
during the process of translation. The secondary structures are held together by
hydrogen bonds. The tertiary structure is held together primarily by hydrophobic
interactions but hydrogen bonds, ionic interactions, and disulfide bonds are usually
involved too.
The process by which the higher structures form is called protein folding and is a
consequence of the primary structure. The mechanism of protein folding is not
entirely understood. Although any unique polypeptide may have more than one stable
folded conformation, each conformation has its own biological activity and only one
conformation is considered to be the active, or native conformation.
The two ends of the amino acid chain are referred to as the carboxy terminus (Cterminus) and the amino terminus (N-terminus) based on the nature of the free group
on each extremity.
Functions
Proteins are involved in practically every function performed by a cell, including
regulation of cellular functions such as signal transduction and metabolism. For
example, protein catabolism requires enzymes termed proteases and other enzymes
such as glycosidases.
Mechanisms of protein regulation
Various molecules and ions are able to bind to specific sites on proteins. These sites
are called binding sites. They exhibit chemical specificity. The particle that binds is
called a ligand. The strength of ligand-protein binding is a property of the binding site
known as affinity.
Since proteins are involved in practically every function performed by a cell, the
mechanisms for controlling these functions therefore depend on controlling protein
activity. Regulation can involve a protein's shape or concentration. Some forms of
regulation include:


Allosteric modulation: When the binding of a ligand at one site on a protein
affects the binding of ligand at another site.
Covalent modulation: When the covalent modification of a protein affects the
binding of a ligand or some other aspect of the protein's function.
Diversity
Proteins are generally large molecules, having molecular masses of up to 3,000,000
(the muscle protein titin has a single amino acid chain 27,000 subunits long). Such
long chains of amino acids are almost universally referred to as proteins, but shorter
strings of amino acids are referred to as "polypeptides," "peptides" or rarely,
"oligopeptides". The dividing line is undefined, though "polypeptide" usually refers to
an amino acid chain lacking tertiary structure which may be more likely to act as a
hormone (like insulin), rather than as an enzyme (which depends on its defined
tertiary structure for functionality).
Proteins are generally classified as soluble, filamentous or membrane-associated (see
integral membrane protein). Nearly all the biological catalysts known as enzymes are
soluble proteins (with a recent notable execption being the discovery of ribozymes,
RNA molecules with the catalytic properties of enzymes.) Antibodies, the basis of the
adaptive immune system, are another example of soluble proteins. Membraneassociated proteins include exchangers and ion channels, which move their substrates
from place to place but do not change them; receptors, which do not modify their
substrates but may simply shift shape upon binding them. Filamentous proteins make
up the cytoskeleton of cells and much of the structure of animals: examples include
tubulin, actin, collagen and keratin, all of which are important components of skin,
hair, and cartilage. Another special class of proteins consists of motor proteins such as
myosin, kinesin, and dynein. These proteins are "molecular motors," generating
physical force which can move organelles, cells, and entire muscles.
Molecular surface of several proteins showing their comparative sizes. From left to
right are: Antibody (IgG), Hemoglobin, Insulin (a hormone), Adenylate Kinase (an
enzyme), and Glutamine Synthetase (an enzyme).
Working with proteins
Proteins are sensitive to their environment. They may only be active in their native
state, over a small pH range, and under solution conditions with a minimum quantity
of electrolytes. A protein in its native state is often described as folded. A protein that
is not in its native state is said to be denatured. Denatured proteins generally have no
well-defined secondary structure. Many proteins denature and will not remain in
solution in distilled water.
One of the more striking discoveries of the 20th century was that the native and
denatured states in many proteins were interconvertible, that by careful control of
solution conditions (by for example, dialyzing away a denaturing chemical), a
denatured protein could be converted to native form. The issue of how proteins arrive
at their native state is an important area of biochemical study, called the study of
protein folding.
Through genetic engineering, researchers can alter the sequence and hence the
structure, "targeting", susceptibility to regulation and other properties of a protein.
The genetic sequences of different proteins may be spliced together to create
"chimeric" proteins that possess properties of both. This form of tinkering represents
one of the chief tools of cell and molecular biologists to change and to probe the
workings of cells. Another area of protein research attempts to engineer proteins with
entirely new properties or functions, a field known as protein engineering.
Protein-protein interactions can be screened for using two-hybrid screening.
Protein and nutrition
Protein is an important macronutrient to the human diet, supplying the body's needs
for nitrogen and amino acids. The exact amount of dietary protein needed to satisfy
these requirements may vary widely depending on age, sex, level of physical activity,
and medical condition. However, the figure of .75g per kilogram of body weight for a
sedentary male is widely given as a daily requirement. Proteins are found in most
food but are particularly concentrated in legumes, nuts, meat, and dairy products. As
it is used, much protein is converted by protein catabolism to ammonia which, due to
its toxicity, must be converted to either urea or uric acid (in some animals) to be
excreted in urine. Protein is the major component of muscles, tendons, enzymes, skin,
hair, eyes, and a tremendous variety of other organs and processes.
The quality of protein intake is important because different proteins supply essential
amino acids in different proportions. Given an adequate intake of nitrogen, the human
body can manufacture 10 of the 18 amino acids from glucose. The remaining 8 amino
acids (threonine, valine, tryptophan, isoleucine, leucine, lysine, phenylalanine, and
methionine) cannot be manufactured by the body and must be acquired through
dietary sources. Thus, they are termed essential amino acids. Proteins possessing
equal proportions of all essential amino acids in relatively abundant quantities are
often termed "complete". Despite this suggestive label, good nutrition need not
depend on upon so-called "complete" proteins because non-complete proteins in
complementary combinations can readily provide the complete spectrum of essential
amino acids. The present method of rating the completeness of protein is known as
the PDCAAS (Protein Digestibility Corrected Amino Acid Score).
Protein deficiency can lead to symptoms such as fatigue, insulin resistance, hair loss,
loss of hair pigment (hair that should be black becomes reddish), loss of muscle mass
(proteins repair muscle tissue), low body temperature, and hormonal irregularities.
Severe protein deficiency, encountered only in times of famine, is fatal.
Excess protein can cause problems as well, such as causing the immune system to
overreact, liver dysfunction from increased toxic residues, bone loss due to increased
acidity in the blood and foundering (foot problems) in horses. The assumption that
high protein diets are bad for bones came from the fact that calium excretion is
increased when dietary protein intake is increased. However, it has recently been
shown that uptake of calcium by the intestine is also increased and as long as calcium
intake is maintained, high protein intake may have benefits for bone in older women
[1]
.
Proteins can often figure in allergies and allergic reactions to certain foods. This is
because the structure of each form of protein is slightly different, and some may
trigger a response from the immune system while others are perfectly safe. Many
people are allergic to casein, the protein in milk; gluten, the protein in wheat and other
grains; the particular proteins found in peanuts; or those in shellfish or other seafoods.
It is extremely unusual for the same person to adversely react to more than two
different types of proteins.
History
The first mention of the word protein, which means of first rank, were from a letter
sent by Jöns Jakob Berzelius to Gerhardus Johannes Mulder on 10. July 1838, where
he wrote:
«Le nom protéine que je vous propose pour l’oxyde organique de la fibrine et
de l’albumine, je voulais le dériver de πρωτειοξ, parce qu’il paraît être la
substance primitive ou principale de la nutrition animale.»
Translated as:
"The name protein that I propose for the organic oxide of fibrin and albumin, I
wanted to derive from [the Greek word] πρωτειοξ, because it appears to be the
primitive or principal substance of animal nutrition."
Investigation of proteins and their properties had been going on since about 1800
when scientists were finding the first signs of this, at the time, unknown class of
organic compounds.