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Amino acids
BIOMEDICAL IMPORTANCE
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In addition to providing the monomer units from which the long polypeptide chains of
proteins are synthesized, the L -α -amino acids and their derivatives participate in
cellular functions as:
diverse as nerve transmission and the biosynthesis of porphyrins, purines, pyrimidines,
and urea.
Short polymers of amino acids called peptides perform prominent roles in the
neuroendocrine system as hormones, hormone-releasing factors, neuromodulators, or
neurotransmitters.
While proteins contain only L -α -amino acids, microorganisms elaborate peptides that
contain both D - and L -α -amino acids. Several of these peptides are of therapeutic
value, including the antibiotics bacitracin and gramicidin A and the antitumor agent
bleomycin.
Certain other microbial peptides are toxic. The cyanobacterial peptides microcystin and
nodularin are lethal in large doses, while small quantities promote the formation of
hepatic tumors.
Humans and other higher animals lack the capability to synthesize 10 of the 20 common
L -α -amino acids in amounts adequate to support infant growth or to maintain health in
adults . Consequently, the human diet must contain adequate quantities of these
nutritionally essential amino acids.
STRUCTURE OF THE AMINO ACIDS
• Although more than 300 different
amino acids have been described in
nature, only twenty are commonly
found as constituents of mammalian
proteins. [These are the only amino
acids that are coded for by DNA, the
genetic material in the cell].
• Each amino acid (except for proline)
has a carboxyl group, an amino
group, and a distinctive side chain
("R-group") bonded to the α-carbon
atom (Figure 1.1 A).
• At physiologic pH (approximately pH
= 7.4), the carboxyl group is
dissociated, forming the negatively
charged carboxylate ion (-COO-), and
the amino group is protonated (NH3+).
Figure 1.1 A
STRUCTURE OF THE AMINO ACIDS
• In proteins, almost all of these carboxyl and
amino groups are combined in peptide linkage
and, in general, are not available for chemical
reaction except for hydrogen bond formation
(Figure 1.1B). Thus, it is the nature of the side
chains that ultimately dictates the role an amino
acid plays in a protein. It is therefore, useful to
classify the amino acids according to the
properties of their side is:
• nonpolar (that is, have an even distribution of
electrons) .
• polar (that is, have an uneven distribution of
electrons, such as acids and bases
Figure 1.1B
Abbreviations and symbols for the
commonly occurring amino acids
Each amino acid name has an associated three-letter
abbreviation and a one-letter symbol. The one-letter codes
are determined by the following rules:
1. Unique first letter: only one amino acid begins with a
particular letter, then that letter is used as its symbol. For
example, I= isoleucine.
2. Most commonly occurring amino acids have priority:
more than one amino acid begins with a particular letter ,
the most common of these amino acids receives this letter
as its symbol. For example, glycine is more common than
glutamate, so G = glycine.
Similar sounding names: Some one-letter symbols sound
like the amino acid they represent. For example, F =
phenylalanine, or W= tryptophan ("twyptophan").
Characteristics of Amino Acids
• There are three main physical categories to describe amino acids:
• 1) Non polar “hydrophobic” nine in all
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Glycine, Alanine, Valine, Leucine, Isoleucine, Methionine,
Proline, Phenylalanine and Tryptophan
• 2) Uncharged polar, six in all
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Serine, Threonine, Asparagine, Glutamine Tyrosine, Cysteine
• 3) Charged polar, five in all
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Lysine, Arginine, Glutamic acid, Aspartic acid, and Histidine
Amino Acids
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You must know:
Their names
Their structure
Their three letter code
Their one letter code
O
H2N
CH
C
OH
CH 2
Tyrosine, Tyr, Y, aromatic, hydroxyl
OH
Classification of amino acids:
a. Non polar :
• Each of these amino acids has a
nonpolar side chain that does
not bind or give off protons or
participate in hydrogen or ionic
bonds.
• The side chains of these amino
acids can be thought of as "oily"
or a property that promotes
hydrophobic interactions.
• In proteins found in aqueous
solutions, the side chains of the
nonpolar amino acids tend to
cluster together in the interior
of the protein.
classification of amino acids:
with uncharged polar side chains:
These amino acids have zero net charge at neutral pH.
1- With side chains containing hydroxylic (OH) groups:
• Serine, threonine, and, rarely, tyrosine contain a polar hydroxyl
group that can serve as a site of attachment for structures such as a
phosphate group. [The side chain of serine is an important
component of the active site of many enzymes.]
with uncharged polar side chains:
3- With side chains containing sulfur
atom:
• The side chain of cysteine contains
a sulfhydryl group (-SH), which is
an important component of the
active site of many enzymes. In
proteins, the -SH groups of two
cysteines can become oxidized to
form a dimer cystine, which
contains a covalent cross-link
called a disulfide bond (-S-S-).
With side chains containing acidic
groups or their amides
The amino acids aspartic and glutamic acid are proton donors. At
neutral pH, the side chains of these amino acids are fully ionized,
containing a negatively charged carboxylate group (-C00-). They are,
therefore, called aspartate or glutamate to emphasize that these
amino acids are negatively charged at physiologic pH .
With side chains containing basic groups
The side chains of the basic amino acids accept protons .At
physiologic pH the side chains of lysine and arginine are
fully ionized and positively charged. In contrast, histidine is
weakly basic and the free amino acid is largely uncharged
at physiologic pH.
Containing aromatic rings
L Histidine ,Phenylalanine, Tyrosine and Tryptophan
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Imino acid (Proline): The side chain of proline
and its α-amino group form a ring structure,
and thus proline differs from other amino acids
in that it contains an imino group, rather than
an amino group.
Proline contributes to the formation of the
fibrous structure of collagen and often
interrupts the α-helices found in globular
proteins
PROPERTIES OF AMINO ACIDS
• The Genetic Code Specifies 20 L -α -Amino Acids
• Of the over 300 naturally occurring amino acids, 20
constitute the monomer units of proteins. While a
non redundant three-letter genetic code could
accommodate more than 20 amino acids, its
redundancy limits the available codons to the 20 L -α
-amino acids classified according to the polarity of
their R groups. Both one- and three-letter
abbreviations for each amino acid can be used to
represent the amino acids in peptides and proteins.
Non standards amino acids :
• Some proteins contain additional amino acids that arise
by modification of an amino acid already present in a
peptide. Examples include conversion of peptidyl
proline and lysine to 4-Hydroxyproline and 5hydroxylysine;
• the conversion of peptidyl glutamate to
γ-carboxyglutamate. These modifications extend the
biologic diversity of proteins by altering their solubility,
stability, and interaction with other proteins.
Selenocysteine, the 21st L -α -Amino
Acid?
• Selenocysteine is an L -α -amino acid found in a
handful of proteins, including certain peroxidases and
reductases where it participates in the catalysis of
electron transfer reactions.
• As its name implies, a selenium atom replaces the
sulfur of its structural analog, cysteine. Since
selenocysteine is inserted into polypeptides during
translation, it is commonly referred to as the "21st
amino acid." However, unlike the other 20 genetically
encoded amino acids, selenocysteine is not specified
by a simple three-letter codon.
Only L -α -Amino Acids Occur in Proteins
• The α-carbon of each amino acid is attached to four different chemical
groups and is, therefore, a chiral or optically active carbon atom. Glycine
is the exception because its α-carbon has two hydrogen substituents and,
therefore, is optically inactive.
• [Amino acids that have an asymmetric center at the α-carbon can exist
in two forms, designated D dextrorotatory and L levorotatory, that are
mirror images of each other (Figure The two forms in each pair are
termed stereoisomers, optical isomers. All amino acids found in proteins
are of the L-configuration.
• Several free L -α -amino acids fulfill important roles in metabolic
processes. Examples include ornithine, citrulline, and argininosuccinate
that participate in urea synthesis; tyrosine in formation of thyroid
hormones; and glutamate in neurotransmitter biosynthesis.
• However, D -Amino acids that occur naturally include free D - serine and
D -aspartate in brain tissue, D -alanine and D -glutamate in the cell walls
of gram-positive bacteria, and D -amino acids in certain peptides and
antibiotics produced by bacteria, fungi, reptiles, and other non
mammalian species.
Amino Acids May Have Positive, Negative, or
Zero Net Charge
• Charged and uncharged forms of the ionizable —COOH and —NH3 + weak
acid groups exist in solution in protonic equilibrium:
• While both R—COOH and R—NH3 + are weak acids, R—COOH is a far
stronger acid than R—NH3+ . At physiologic pH (pH 7.4), carboxyl groups
exist almost entirely as R—COO– and amino groups predominantly as R—
NH3+ .
Figure 3–1 illustrates the effect of pH on the charged state of aspartic acid.
zwitterions
• Molecules that contain an equal number of ionizable
groups of opposite charge and that therefore bear no net
charge are termed zwitterions. Amino acids in blood and
most tissues thus should be represented as in A, below.
• Structure B cannot exist in aqueous solution because at any
pH low enough to protonate the carboxyl group, the amino
group would also be protonated. Similarly, at any pH
sufficiently high for an uncharged amino group to
predominate, a carboxyl group will be present as R—COO– .