Download Chemistry 501 Lecture 3 Amino Acids

Amino Acids,
Peptides
Amino Acids
Amino acids
• are the building blocks of proteins.
• contain a carboxylic acid group and an amino
group on the alpha () carbon.
• are ionized in solution.
• each contain a different side group (R).
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• Amino acids are derivatives of carboxylic acids
formed by substitution of -hydrogen for amino
functional group.
• Composed of C, H, O, N usually
S, P
• Always has a NH2
All the standard amino acids except
(glycine) the α carbon is asymmetric.
α carbon is bonded to four different
substituent groups:
carboxyl group
amino group
R group
hydrogen atom.
• All amino acids
start with this
structure
• The “R” stands
for “anything”
Classification of Amino Acids
CLASSIFICATION:
Classified based on the properties
of their R groups.
Tendency to interact with water at
biological pH (near pH 7.0).
those whose R groups are:
1)nonpolar and aliphatic
2)aromatic (generally nonpolar)
3) polar but uncharged
4) negatively charged
5) positively charged.
Within each class, there are
gradations of polarity, size, and
shape of the R groups.
• nonpolar (hydrophobic)
Nonpolar
with hydrocarbon side
chains.
• polar (hydrophilic) with
polar or ionic side chains.
Acidic
• acidic (hydrophilic) with
acidic side chains.
• basic (hydrophilic) with
–NH2 side chains.
Polar
Basic
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Nonpolar
Acidic
Polar
Basic
1) Nonpolar Aliphatic R group:
The hydrocarbon R groups are
nonpolar and hydrophobic.
The bulky side chains of alanine,
valine, leucine, and isoleucine,
promote hydrophobic interactions
within protein structures.
Nonpolar Amino Acids
An amino acid is nonpolar when the R group
is H, alkyl, or aromatic.
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Amino acids can be classified by R groups
2) Polar, Uncharged R Groups :
Are more soluble in water than nonpolar
amino acids, because they contain functional
groups that form hydrogen bonds with water.
Includes:
I. Serine(OH)
II. Threonine(OH)
III. Cysteine( S)
IV.Methionine(S, sulphur atom)
V. Asparagine(NH2, amide group)
VI.Glutamine. (NH2)
Polar Amino Acids
An amino acid is polar when the R group is an
alcohol, thiol, or amide.
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3) Aromatic R Groups:
Phenylalanine (Phe), Tyrosine (tyr), and
Tryptophan (Trp), are relatively nonpolar.
The OH group of tyrosine can form hydrogen
bonds, hence important functional group in the
activity of some enzymes.
Tyrosine and tryptophan are more polar than
phenylalanine because of the tyrosine hydroxyl
group and the nitrogen of the tryptophan indole
ring.
Tryptophan and tyrosine, and phenylalanine
absorb ultraviolet light.
indole
ring
4) Negatively Charged (Acidic)
R Groups:
Include:
1) Aspartate
2) Glutamate
Each have a second carboxyl group.
These are the parent compounds of
asparagine and glutamine.
5) Positively Charged (Basic) R
Groups:
Includes:
lysine, has a second amino group at the e
position on its aliphatic chain;
Arginine, which has a positively charged
guanidino group;
Histidine, has an imidazole group.
imidazole
guanidino
Acidic and Basic Amino Acids
An amino acid is
• acidic when the R group is a carboxylic
acid.
• basic when the R group is an amine.
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Essential Amino Acids
Clue to remember: PVT TIM HALL
Proteinaceous AA − proteins consist of 20 AA.
• Essential − organism is not able to synthesize these AA but
accept from food.
• Nonessential − organism produced from essential AA by
transamination.
•
•
•
•
•
Phenylalanine
Valine
Threonine
Tryptophan
Isoleucine
•
•
•
•
•
Methionine
Histidine
Arginine
Lysine
Leucine
Description –
general properties
GENERAL PROPERTIES OF
AMINO ACIDS:
1) Isomerism:
Two types:
1) L form
2) D forms.
stereo-isomerism: all amino acids except glycine
exist as D and L- isomers.
- In D-amino acids, -NH2 group (right). In animals
and plants.
- In L-amino acids (left) ,occur in bacteria.
Amino Acids
Steric relationship
of the
stereoisomers of
Alanine to the
absolute
configuration of Land Dglyceraldehyde
The amino acid residues in proteins are the L isomers
• AA are optically active molecules and asymmetry of their
mirror images is not superimposable (except in the case of
glycine where the R-group is hydrogen)
• according new UIPAC
nomenclature L- D- forms
were replaced for (S)- and (R)system
2) Ionization:
Amino acids in aqueous solution are
ionized and can act as acids or bases.
Those having a single amino group and
a single carboxyl group crystallize from
neutral aqueous solutions as fully ionized
species known as zwitterions (German
for "hybrid ions"), each having both a
positive and a negative charge.
• Zwitterionic structure is neutral and its
value of pH is called isoelectric point.
3) Amphoteric nature:
Amino Acids Can Act as Acids and as
Bases.
When a crystalline amino acid, such as
alanine, is dissolved in water, it exists in
solution as the dipolar ion, or
zwitterion, which can act either as an
acid (proton donor), or as a base (proton
acceptor)
• majority of amino acids has
amphoteric character – functional
group –COOH is the reason of acidity
and –NH2 group causes basic
properties.
• in basic environment AA dissociate
proton to form carboxyl anion –COO .
Basic surround defends –NH2 against
dissociation.
• in basic environment AA dissociate
proton to form carboxyl anion –COO .
Basic surround defends –NH2 against
dissociation.
• in acidic environment AA accept
+
proton to form amonium cation –NH3 .
Acidic environment defends –COOH
against dissociation.
• Physical propeties – AA are colourless crystalline
substances soluble in water and insoluble in organic
solvents with high melting point.
Arginine
Valine
Alanine
Lysine
Reactions of amino acids
Polymerization – form peptides, proteins and enzymes
• A condensation reaction between the carboxyl of one amino
acid and the amino group of another forms a peptide bond.
Peptides
• Oligopeptides − condensation of 2 – 10 AA units
• Polypeptides − condensation of 11 – 100 AA units
Proteins − more than 100 AA units
• Disulfide linkage – conversion of cysteine to cystine is
like a conversion of thiols to disulfides by mild oxidizing
agents. This conversion can be reversed by mild
reducing agents.
• Disulfide bonds stabilize protein structure by providing
cross-link.
Reversible formation of disulfide bond by the
oxidation of two molecules of cysteine
e.g. two polypeptide chains of insuline
Peptides
The Peptide Bond
• Amino acids can be linked together by
covalent bonds
• The bonds are formed between the carboxyl group of one amino acid and the
-amino group of the next one
• Water is removed in the process and the
linked amino residues remain attached to
one another
• This bond is called a peptide bond and
peptides are formed
• When hundreds of amino acids are joined in
this process, a polypeptide is formed
• The compound formed may also be referred to
as an amide
• The bond formed between the carbon and
nitrogen is a single bond
The Peptide Bond
Pentapeptide
hydrolysis
condensation
Two amino acid molecules
can be covalently joined
through a substituted
amide linkage, termed a
peptide bond, to yield a
dipeptide
Serylglyciltyrosylalanylleucine
or
Ser-Gly-Tyr-Ala-Leu
or
SGYAL
Peptides are named beginning with the aminoterminal
residue, which by convention is placed at the left.
just a few residues  oligopeptide
many residues  polypeptide
Some Small Peptides of Physiological
Interest
Simplest combination of amino acids are dipeptides in
which two amino acids are linked together
• An example is the dipeptide carnosine which is found in
muscle tissue
The compound is also known as -alanyl-L-histidine
The peptide bond is formed between the carboxyl group of
the -alanine and the amino group of histidine
• Aspartame is another dipeptide which has health
implications
• Glutathione a tripeptide is a scavenger for oxidizing agents
• Glutathione is -glutamyl-L-cystenylglycine
• Two pentapeptides found in the brain are enkaphalins which
are natural analgesics
– Tyr-Gly-Gly-Phe-Leu (leucine enkaphalin)
– Tyr-Gly-Gly-Phe-Met (Methionine enkaphalin)
• Opiates bind to the same receptors in the brain intended for
the enkaphalins and hence produce their physiological
activities
• Oxytocin and vasopressin have cyclic structures
• Each has 9 amino acid residues and an amide group at the
C-terminal and disulfide bonds at positions 1 and 6
There are several levels of protein structure
Particularly stable arrangements of
amino acid residues giving rise to
recurring structural paterns
Includes disulfide bonds
Multisubunit proteins
Arrangement is space of
polypeptide subunits
All aspects of the 3-D folding
of a polypeptide
Uncommon amino acids also have important functions
prothrombim,
a # of Ca+ binding proteins
plant cell wall,
collagen
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3
5
2



1
elastin
collagen
Lysine
residues
myosin
Residues created by modification of common residues already incorporated into a polypeptide
rare, introduced during protein
synthesis rather than created
through a postsynthetic modification
~ 300 additional amino acids
have been found in cells
Reversible amino acid modifications involved in regulation of protein activity
Examples of Clinical
Aminoacidurias
• Metabolic defects: Phenylketonuria (Phe),
Tyrosinemias (Phe,Tyr), Maple Syrup Urine
Disease (Leu, Val, Ile), Alcaptonuria (Tyr)
• Absorption/transport defects: cystinuria (Cys),
Hartnup disease , Fanconi’s Syndrome
• These diseases are generally diagnosed from
indicators in the urine or plasma.