Download Polar amino acids with negative charge

Chapter: 6
Amino acids
Dr. Gobinath Pandian
INTRODUCTION
Amino acids are molecules containing an amine
group (NH), a carboxylic acid group (COOH) and a
side chain(R) that varies between different amino
acids. These molecules contain the key elements
of carbon, hydrogen, oxygen, and nitrogen.
• Any of a class of organic compounds in which a carbon atom
has bonds to an amino group (-NH2), a carboxyl group (-COOH),
a hydrogen atom (-H), and an organic side group (called -R).
• Amino acids are organic compounds made of carbon,
hydrogen, oxygen, nitrogen, and (in some cases) sulfur bonded
in characteristic formations.
• They are therefore both carboxylic acids and amines. The
physical and chemical properties unique to each result from
the properties of the R group, particularly its tendency to
interact with water and its charge (if any).
• Amino acids joined linearly by peptide bonds (see covalent
bond) in a particular order make up peptides and proteins.
• Amino acids are critical to life, and have
many functions in metabolism. One
particularly important function is to serve as
the building blocks of proteins, which are just
linear chains of amino acids, or more
precisely, amino acid residues.
• Every protein is chemically defined by the
order of amino acid residues, their primary
structure and this, in turn, determines their
secondary structure
Glycine is the smallest of the amino acids. It is ambivalent, meaning that it
can be inside or outside of the protein molecule. In aqueous solution at or
near neutral pH, glycine will exist predominantly as the zwitterion
The isoelectric point or isoelectric pH of glycine will be centered between the
pKas of the two ionizable groups, the amino group and the carboxylic acid
group.
In estimating the pKa of a functional group, it is important to consider the
molecule as a whole. For example, glycine is a derivative of acetic acid, and
the pKa of acetic acid is well known. Alternatively, glycine could be considered
a derivative of aminoethane.
Cysteine is one of two sulfur-containing amino acids; the other is methionine.
Cysteine differs from serine in a single atom-- the sulfur of the thiol replaces
the oxygen of the alcohol.
The amino acids are, however, much more different in their physical and
chemical properties than their similarity might suggest.
Cysteine also plays a key role in stabilizing extracellular proteins. Cysteine can
react with itself to form an oxidized dimer by formation of a disulfide bond.
The environment within a cell is too strongly reducing for disulfides to form,
but in the extracellular environment, disulfides can form and play a key role in
stabilizing many such proteins, such as the digestive enzymes of the small
intestine.
• Methionine, an essential amino acid, is one of the two sulfurcontaining amino acids. The side chain is quite hydrophobic and
methionine is. usually found buried within proteins.
• Unlike cysteine, the sulfur of methionine is not highly
nucleophilic, although it will react with some electrophilic centers.
It is generally not a participant in the covalent chemistry that
occurs in the active centers of enzymes.
• Methionine as the free amino acid plays several important roles in
metabolism. It can react to form S-Adenosyl-L-Methionine (SAM)
which servers at a methyl donor in reactions
• Alanine is a hydrophobic molecule. It is ambivalent,
meaning that it can be inside or outside of the protein
molecule. The α carbon of alanine is optically active; in
proteins, only the L-isomer is found.
• Note that alanine is the α-amino acid analog of the αketo acid pyruvate, an intermediate in sugar metabolism.
Alanine and pyruvate are interchangeable by a
transamination reaction.
• Asparagine is the amide of aspartic acid. The
amide group does not carry a formal charge under
any biologically relevant pH conditions. The amide
is rather easily hydrolyzed, converting asparagine
to aspartic acid.
• Asparagine has a high propensity to hydrogen
bond, since the amide group can accept two and
donate two hydrogen bonds.
• Asparagine is a common site for attachment of
carbohydrates in glycoproteins.
• Aspartic acid is one of two acidic amino acids. Aspartic acid and
glutamic acid play important roles as general acids in enzyme
active centers, as well as in maintaining the solubility and ionic
character of proteins.
• Proteins in the serum are critical to maintaining the pH balance
in the body; it is largely the charged amino acids that are
involved in the buffering properties of proteins.
• Aspartic acid and oxaloacetate are interconvertable by a simple
transamination reaction, just as alanine and pyruvate are
interconvertible.
• Glutamine is the amide of glutamic acid, and is uncharged
under all biological conditions.
• The additional single methylene group in the side chain
relative to asparagine allows glutamine in the free form or
as the N-terminus of proteins to spontaneously cyclize and
deamidate yielding the six-membered ring structure
pyrrolidone carboxylic acid, which is found at the Nterminus of many immunoglobulin polypeptides. This
causes obvious difficulties with amino acid sequence
determination.
• Histidine, an essential amino acid, has as a positively
charged imidazole functional group.
• The imidazole makes it a common participant in enzyme
catalyzed reactions.
• The unprotonated imidazole is nucleophilic and can serve
as a general base, while the protonated form can serve as
a general acid. The residue can also serve a role in
stabilizing the folded structures of proteins.
• Isoleucine, an essential amino acid, is one of the three amino acids
having branched hydrocarbon side chains. It is usually
interchangeable with leucine and occasionally with valine in
proteins.
• The side chains of these amino acids are not reactive and therefore
not involved in any covalent chemistry in enzyme active centers.
• However, these residues are critically important for ligand binding
to proteins, and play central roles in protein stability. Note also that
the β carbon of isoleucine is optically active, just as the β carbon of
threonine. These two amino acids, isoleucine and threonine, have in
common the fact that they have two chiral centers.
• Leucine, an essential amino acid, is one of the three
amino acid with a branched hydrocarbon side chain.
• It has one additional methylene group in its side chain
compared with valine.
• Like valine, leucine is hydrophobic and generally buried
in folded proteins.
• Lysine. an essential amino acid, has a positively charged ε-amino
group (a primary amine).
• Lysine is basically alanine with a propylamine substituent on
theβcarbon. The ε-amino group has a significantly higher pKa (about
10.5 in polypeptides) than does the α-amino group.
• The amino group is highly reactive and often participates in a
reactions at the active centers of enzymes. Proteins only have one α
amino group, but numerous ε amino groups
• Phenylalanine, an essential amino acid, is a derivative of
alanine with a phenyl substituent on the β carbon.
Phenylalanine is quite hydrophobic and even the free amino
acid is not very soluble in water.
• Due to its hydrophobicity, phenylalanine is nearly always found
buried within a protein. The π electrons of the phenyl ring can
stack with other aromatic systems and often do within folded
proteins, adding to the stability of the structure.
• Proline shares many properties with the aliphatic group.
• Proline is formally NOT an amino acid, but an imino acid.
Nonetheless, it is called an amino acid. The primary amine on
the α carbon of glutamate semialdehyde forms a Schiff base
with the aldehyde which is then reduced, yielding proline.
• When proline is in a peptide bond, it does not have a hydrogen
on the α amino group, so it cannot donate a hydrogen bond to
stabilize an α helix or a β sheet. It is often said, inaccurately,
that proline cannot exist in an α helix. When proline is found in
an α helix, the helix will have a slight bend due to the lack of
the hydrogen bond.
• Serine differs from alanine in that one of the
methylenic hydrogens is replaced by a hydroxyl
group.
• Serine is one of two hydroxyl amino acids. Both are
commonly considered to by hydrophilic due to the
hydrogen bonding capacity of the hydroxyl group.
• Threonine, an essential amino acid, is a hydrophilic molecule.
• Threonine is an other hydroxyl-containing amino acid. It differs
from serine by having a methyl substituent in place of one of
the hydrogens on the β carbon and it differs from valine by
replacement of a methyl substituent with a hydroxyl group.
• Note that both the α and β carbons of threonine are optically
active.
• Tryptophan, an essential amino acid, is the largest of
the amino acids. It is also a derivative of alanine,
having an indole substituent on the β carbon.
• The indole functional group absorbs strongly in the
near ultraviolet part of the spectrum. The indole
nitrogen can hydrogen bond donate, and as a result,
tryptophan, or at least the nitrogen, is often in contact
with solvent in folded proteins.
• Tyrosine, an essential amino acid, is also an aromatic amino acid and is
derived from phenylalanine by hydroxylation in the para position.
•
While tyrosine is hydrophobic, it is significantly more soluble that is
phenylalanine. The phenolic hydroxyl of tyrosine is significantly more
acidic than are the aliphatic hydroxyls of either serine or threonine,
having a pKa of about 9.8 in polypeptides.
•
As with all ionizable groups, the precise pKa will depend to a major
degree upon the environment within the protein.
• Tyrosines that are on the surface of a protein will generally have a lower
pKa than those that are buried within a protein; ionization yielding the
phenolate anion would be exceedingly unstable in the hydrophobic
interior of a protein.
• Valine, an essential amino acid, is hydrophobic, and as
expected, is usually found in the interior of proteins.
• Valine differs from threonine by replacement of the
hydroxyl group with a methyl substituent. Valine is often
referred to as one of the amino acids with hydrocarbon
side chains, or as a branched chain amino acid.
• Note that valine and threonine are of roughly the same
shape and volume. It is difficult even in a high resolution
structure of a protein to distinguish valine from
threonine.
• Glutamic acid has one additional methylene group in its side chain
than does aspartic acid. The side chain carboxyl of aspartic acid is
referred to as the β carboxyl group, while that of glutamic acid is
referred to as the γ carboxyl group.
• The pKa of the γ carboxyl group for glutamic acid in a polypeptide is
about 4.3, significantly higher than that of aspartic acid.
• In some proteins, due to a vitamin K dependent carboxylase, some
glutamic acids will be dicarboxylic acids, referred to as γ
carboxyglutamic acid, that form tight binding sites for calcium ion.
• Arginine, an essential amino acid, has a positively charged guanidino
group. Arginine is well designed to bind the phosphate anion, and is
often found in the active centers of proteins that bind phosphorylated
substrates.
• As a cation, arginine, as well as lysine, plays a role in maintaining the
overall charge balance of a protein.
• There are 6 codons in the genetic code for arginine, yet, although this
large a number of codons is normally associated with a high frequency
of the particular amino acid in proteins, arginine is one of the least
frequent amino acids.
• The discrepancy between the frequency of the amino acid in proteins
and the number of codons is greater for arginine than for any other
amino acid.
Non-polar amino acids
• They have equal number of amino and carboxyl
groups and are neutral.
• These amino acids are hydrophobic and have no
charge on the 'R' group. The amino acids in this
group are alanine, valine, leucine, isoleucine,
phenyl alanine, glycine, tryptophan, methionine
and proline.
Non-polar amino acids
Polar amino acids with no charge
• These amino acids do not have any charge on
the 'R' group. These amino acids participate in
hydrogen bonding of protein structure.
• The amino acids in this group are - serine,
threonine, tyrosine, cysteine, glutamine and
aspargine
Polar amino acids with no charge
Polar amino acids with positive charge
• Polar amino acids with positive charge have
more amino groups as compared to carboxyl
groups making it basic.
• The amino acids, which have positive charge on
the 'R' group are placed in this category. They
are lysine, arginine and histidine.
• Polar amino acids with negative charge
• Polar amino acids with negative charge have
more carboxyl groups than amino groups making
them acidic.
• The amino acids, which have negative charge on
the 'R' group are placed in this category. They are
called as dicarboxylic mono-amino acids. They
are aspartic acid and glutamic acid.
Types of Amino acids
1. Aromatic group
2. Aliphatic group
3. Sulphur Containing amino acids
4. Hydrophylic amino acids
• Aromatic amino acids are normally hydrophobic and includes
phenylalanine, tyrosine and tryptophan.
•
Aliphatic amino acids are basically hydrophobic and an be
located in core of protein. glycine ,valine, alanine, leucine,
proline and isoleucine are aliphatic amino acids.
• sulphur containing amino acids include sulphur atom and
cysteine and methionine are the examples.
• Hydrophilc amino acids are further categorized as
acidic ,neutral and basic amino acids. Acidic amino
acids are highly polar and are always negatively
charged. Aspartate and glutamate are the examples.
• Basic amino acids contains side chains that are
positively charged . lysine,arginine and histidine are the
examples.
• Neutral amino acids are polar in nature and serine
,threonine, asparagine and glutamine are the
examples.