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Introduction to
Amino Acids
of Medical Importance
What Amino
are Amino
acidsAcids
Amino Acids are the building blocks of
proteins
ONLY 20 amino acids
(out of 300 in nature) are present in
human body
(that are coded for by DNA)
What is an Amino Acid
•
Amino acid is an organic acid which contains both an acidic carboxyl group (COOH) and a basic amino group (-NH2).
•
In most natural amino acids, the amino group is attached to the
a-carbon atom i.e. the carbon atom adjacent to the carboxyl group
So, they are called a amino acids
General formula of amino acids in humans
COOH
I
a carbon
NH2 – C - H
I
R
At physiological pH (approximately pH 7.4), in free amino acids:
Carboxyl group is dissociated to (-COO-)
& amino group is positively charged (-NH3+)
This Carbon is called
α-carbon
There are 20 common
amino acids that make up
almost all proteins.
Each has a carboxyl group &
an amino group bonded to
the same carbon atom.
Each has a different side
chain, or R group.
Classification of amino acids
• polar & non polar (according to the side chain properties)
• Essential & non essential (according to being synthesized or not )
• Glucogenic, ketogenic & both (according to metabolic fate)
Classification of amino acids according to
side chains properties
•
At physiological pH (approximately pH 7.4), in free amino acids:
Carboxyl group is dissociated to (-COO-) & amino group is positively charged (-NH3+)
• In proteins
almost all of these carboxyl & amino groups are combined in peptide bond
Carboxyl & amino groups of peptide bond do not share in chemical reactions of amino
acids EXCEPT for hydrogen bonding
So, it is the nature of the side chains that determines the role of an amino acid in a protein.
Accordingly, amino acids are classified according to properties of their
side chains i.e. whether they are polar or nonpolar
Amino acids with nonpolar side chains
•
Each of these amino acids has a non-polar side chain that does not
participate in hydrogen or ionic bonds
(i.e. hydrophobic : they do not bind with water)
•
Location of nonpolar amino acids in proteins:
in proteins found in aqueous solutions (a polar environment), the side
chains of the nonpolar amino acids tend to cluster together in the interior
of the protein due to the hydrophobic nature of the nonpolar side chains
(R-groups).
Accordingly, the nonpolar R-groups thus fill up the interior of the folded
protein
These side chains
are nonpolar
& tend to cluster
together
within proteins
stabilizing protein
structure via
hydrophobic
interactions
Amino acids with uncharged polar side chains
•
•
These amino acids have zero net charge at neutral pH (uncharged)
They can form bonds (interactions) with water i.e. hydrophilic
They are:
• Serine, threonine & tyrosine each contains a polar hydroxyl group that can
participate in hydrogen bond formation (so, they are hydrophilic)
•
Aspargine & glutamine each contains a carbonyl group & an amide group, both
of which can participate in hydrogen bonding. (so, they are hydrophilic)
•
Cysteine contains sulfhydryl (–SH) group which are oxidized to form a dimer
cystine that contains covalent cross-link called a disulfide bond –S-S-
The R groups of
these amino acids
are
hydrophilic because
they contain
functional groups
that form H bonds
with water
Cysteine can be oxidized to form a covalently linked dimeric amino acid,
cystine
Amino acids with negatively charged side chains
• Amino acids aspartic acid & glutamic acid have carboxyl groups
(COOH) side chains
• At physiological pH, (-COOH) side chains of these amino acids are
negatively charged ( –COO-).
So, they are called acidic amino acids.
& are hydrophilic (polar) i.e. can form interaction (bond) with water.
Amino acids with positively charged side chains
• Amino acids lysine & argenine have amino group (-NH2) side chains
• At physiologic pH, (- NH2) side chains of these amino acids are
positively charged(-NH3+).
So, they are called basic amino acids.
& they are hydrophilic (polar) i.e. can form interaction (bond) with
water.
• Histidine is weakly basic.
Essential amino acids
These are amino acids that can NOT be synthesized in the human body.
So, they MUST be supplied in diet.
They are:
Methionine
Threonine
Valine
Isoleucine
Phenylalanine
Tryptophan
Leucine
Lysine
Argenine & histidine are semi-essential amino acids (synthesized in the
body in insufficient amounts)
Some important properties of amino acids
1- Optical activity of amino acids
The a-carbon of each amino acid is attached to four different chemical
groups (with exception of glycine , its a-carbon is attached to two hydrogen)
- So, they can exist in two forms called as D & L that are mirror images of
each other
-
- The two forms in each pair are termed sterioisomers, optical isomers or
enantiomers
- All amino acids found in proteins are of the L-amino
acids
- D-amino acids are found in some antibiotics, in plant & bacterial cell walls
D- & L- amino acids
Some Important
important Properties
properties of
Some
of amino
Amino acids
Acids (cont.)
(cont.)
2- The isoelectric point
•
At certain pH, an amino acid form Zwitterion (dipolar ions) i.e. an ion carrying
both negative & positive charge & hence, is electrically neutral.
•
So, it will not migrate to cathode or anode
•
The pH at which a zwitterion is formed is called isoelectric point.
Each amino acid has its own isoelectric point
- At which, it carries zero net charge (+ve = -ve) & will not migrate to anode or cathode
- Above which, amino acids will carry a negative charge
- Below which, it will carry a positive charge .
Introduction to
Proteins
of Medical Importance
Importance of Proteins
1- Proteins form the building units of all body cells
2-Almost all enzymes are protein in nature
3- Many hormones are protein in nature as insulin and thyroxine
4- Certain biological compounds necessary for maintenance of life as
hemoglobin, myoglobin etc are protein substances
5- Immnuoglobulins (antibodies) present in body are protein in nature
6- Osmotic pressure of plasma proteins is necessary for exchange of fluids
between the blood and interstitial fluid
Structure of protein
Proteins have four levels of structure
Primary structure
Definition:
is the sequence of amino acids in a protein.
Importance:
for studying genetic diseases
(that results from proteins of abnormal amino acid sequence i.e. abnormal primary structure)
Peptide bonds:
In proteins, amino acids are joined covalently by peptide bonds to form a polypeptide chain
Peptide bonds: 1- formed by a linkage between a-carboxyl group of one amino acid and
the a-amino group of adjacent amino acid
2- They are broken by enzymatic hydrolysis
3- They are not lost by denaturation
Polypeptide chain:
is a chain formed from joining of amino acids by peptide bonds leaving two free ends :
the amino terminal or N-terminal (with free amino group) and a carboxyl terminal ,
C-terminal (with a free carboxyl group) .
The sequence of a polypeptide chain starts from the amino terminal
Polypeptide Chain
Secondary structure
Definition:
is the arrangement of adjacent amino acids that are located near to each
other in the linear sequence (polypeptide)
Examples of these arrangements: a helix, b-sheet
a-helix:
- A spiral structure
- Each turn of a-helix contains 3-4 amino acids
- Helix is stabilized by hydrogen bonds.
b-sheet
Composed of segments of fully extended polypeptide chains joined with
hydrogen bonding perpendicular to polypeptide backbone
Secondary structure (cont.)
Motifs (supersecondary structure):
- Combining secondary structural elements (a-helix, b-sheets
& nonrepetitive sequences)
- Combining of motifs will form a domain which is:
the functional and three dimensional structural unit of a
polypeptide
So,
the secondary structure is formed of combining of
a-helix, b-sheet to form
a motif
Motifs combine to form
a domain
Tertiary structure
Definition:
Refers to folding of domains and the final arrangement of domains in a
polypeptide
Polypeptide chains more than 200 amino acids in length generally consists at least
two domains
Tertiary structure is stabilized by:
1- Disulfide bonds: between –SH groups of two cysteine amino acids
2- Hydrophobic interactions: between amino acids with nonpolar side chains
3- Hydrogen bonds
4- Ionic interactions: between COO- of aspartate or glutamate with –NH3+ of lysine
bonds stabilizing tertiary structure
A protein structure
with primary, secondary
& tertiary levels of
structure
Primary structure (amino acid sequence )
Secondary structure (coiling)
Tertiary structure (folding)
Quaternary structure
Definition:
The arrangements of more than one polypeptide subunit in a protein is called
quaternary structure of protein
Monomeric proteins:
Proteins consists of only one polypeptide chain (subunit)
(as for example myoglobin)
Polymeric proteins (dimeric, trimeric or tetrameric, etc):
Proteins contain more than one polypeptide chain (subunits)
(as for example hemoglobin which is tetrameric)
•
Subunits are held together by noncovalent interactions (as hydrogen, ionic bonds)
•
Subunits may work cooperatively with each other (as in hemoglobin) or work
independently of each other.
Some important properties of proteins
1- Solubility of proteins in water:
•
•
Most proteins are soluble in water and insoluble in nonpolar fat solvents.
Scleroproteins are insoluble in water.
2- Amphoteric properties of proteins:
•
Proteins contain free carboxyl and amino groups at the ends of the peptide
chains. This makes proteins react with acids and alkalies (i.e. amphoteric)
•
Each protein has its own isoelectric point which is the pH at which it carries equal
positive and negative charge.(neutral)
On the acid side of the isoelectric point (lower pH), proteins carries positive
charge while on the alkaline side (higher pH) they carry negative charge.
Some important properties of proteins
3- Denaturation of proteins:
is the destruction of the secondary and tertiary structures of protein molecule
without loss of the primary structure (peptide bonds).
Effects of denaturation of proteins:
1-Loss of biological activities of proteins
2- Permanent disorder (irreversible) in common cases (reversible in rare cases).
Denaturation can be produced by:
1-Physical agents as heat, ultaviolet rays, X rays… etc
2-Chemical agents: as strong acids, alkalies, heavy metals
N.B. Protreolytic enzymes (e.g. enzymes of digestion) hydrolyse the polypeptide chain (destruct peptide bond
leading to loss of the primary .level of protein structure). This is different from denaturation.
Classification of proteins
1-
Simple proteins
on hydrolysis, simple proteins yield amino acids only.
2-
Conjugated proteins
On hydrolysis they yield amino acids & a non protein part (prosthetic group)
3- Derived
proteins
They are decomposition products of proteins
Simple proteins (examples)
On hydrolysis, simple proteins yield amino acids only.
Albumin & globulins
- available in milk and egg (of high nutritional value)
- In blood they are two of the plasma proteins.
Histones
- a basic protein as it is rich in histidine.
- available with nucleic acids in chromosomes and in the globin part of hemoglobin.
Scleroproteins
They are the most resistant proteins.
They form the protective and supportive proteins of the body
include:
1-Collagen in tendons, cartilage, bones and connective tissue.
2- Elastin in elastic fibers in lung and big arteries
3- Reticulin in reticular connective tissues of liver, spleen and kidney
4- Keratin in hair, nails and skin
Conjugated proteins (examples)
These proteins on hydrolysis give amino acids and non protein parts called the prosthetic groups
Phosphoproteins
Proteins that are combinedwith phosphoric acid
Example: caseinogen of milk
Glycoprotein
They consists of proteins + mucopolysaccharides (carbohydrates)
They occur in mucous secretions, cartilage, bone & connective tissues.
Examples: Cholndroitin sulphate, Mucoitin sulphate & heparin
Chromoproteins
As hemoglobin in blood and myoglobin of muscles
Hemoglobin & myoglobin are composed of protein part (globin) & non protein part (heme).
Lipoproteins
Lipoproteins are conjugated proteins containing proteins & lipids.
Plasma lipoproteins transport lipids in blood.
Nucleoproteins
They are composed of basic proteins as histones and nucleic acid (DNA of chromosomes).