Download Amino acids and peptide bonds

Chapter 4
Amino Acids
Amino acids
-20 common amino acids there are others found
naturally but much less frequently
Common structure for amino acid
COOH, -NH2, H and R functional groups all
attached to the alpha carbon
Ionization of amino acids
Three possible forms (not counting R group)
depending on pH
Amino Acids
Common amino acids are known as alphaamino acids
Primary –NH2 replaces a H in the alpha
carbon atom
Soul exception – proline
has secondary amino group (-NH-)
Amino acids readily ionize and are dipolar
ions
2
Amino Acid Basics
pKa of the amino and carboxy differ based on R group and
microenvironment. See table 4-1 pp 80 (2nd ed) pp 76-7 (3rd ed).
– The average is about 2.1 for the alpha carboxyl and 9.7 for the
alpha amino groups
- Amino acids are zwitterions - a molecule with both a pos and neg
charge
- All naturally occurring amino acids are optically active isomers,
except glycine.
- R-groups determine the functionality of the amino acids.
All amino acids can be based on one of three basic groups, non-polar,
uncharged polar and charged polar (table 4-1).
Also are classified based on hydrophobicity, reactivity, acidic and basic
nature, relative size of the side groups
Non-Polar Amino Acids
Glycine, alanine, valine, leucine and isoleucine: Aliphatic, inert.
These are very hydrophobic amino acids with various sized side
groups.
Valine, leucine and isoleucine are branched chain and bulky and can
cause steric hindrance. These amino acids have a large effect on
the structure of proteins
COOH NH2 R-Group
Non-Polar Amino Acids
Proline is the only aa where the alpha amino group is tied up
in a ring structure. This amino acid is only slightly
hydrophobic.
The ring structure decreases the flexibility of the peptide
backbone.
COOH NH2
R-Group
Phenylalanine, tyrosine and tryptophan
All are aromatic rings. Pi bonds /
e- clouds create a very hydrophobic
aa. Phenylalanine is very low in
relative concentrations.
Trp and Tyr absorb at 280 nm.
Peptide backbone absorb at 260 nm.
Tyrosine is very reactive and is often
phosphorylated at the OH.
These aas contain phenyl and indol
rings.
COOH NH2
R-Group
Methionine and Cysteine
COOH NH2
R-Group
Hydrophobic amino acids contain
sulfur. The cysteine is very
reactive and involved in the
structure of the protein.
Involved in disulfide bonds when
oxidized.
Asparate, glutamate asparagine and glutamine
. All are acidic, hydrophilic and the side groups are
involved in H bonding.
COOH NH2
R-Group
Lysine, arginine and histadine
These are basic Hydrophilic amino acids.
Both the guanidino group of arginine and the imidazole ring of histadine
contain resonance forms.
The histadine is the only amino acid with a side group pKa in the
physiological pH range. It is often found in sites of catalysis (very
reactive). His also is a good chelator of divalent transition metals
Zn+2 and NI+2 .
COOH NH2
R-Group
Serine and threonine
-
Only slightly hydrophilic.
-
The OH is only ionizable under very basic conditions.
-
The OH groups are very reactive and are phosphorylated similar
to tyrosine.
COOH NH
R-Group
2
Less Common Amino Acids
Here are some amino acids that are
found in proteins, but are
comparatively rare.
They are not synthesized by ribosomal
processes; most typically arise from
post-translational modifications to the
protein, which are catalyzed by
specific enzymes.
Common post-translational
modifications include hydroxylation,
methylation, acetylation, and
phosphorylation.
You are not responsible for knowing
these amino acids, however, if asked
you should be able to recognize that
they are not one of the common 20.
More
titrations
When the amino acid is
has a 0 net charge
that is considered
the isoelectric point.
For amino acids with
side groups that
contain an ionizable
moiety it is the
average of the two
pKa that are
charged when the
net charge is zero.
Isoelectric Points
If the side group is not ionizable, then the pI is the
average of the C and N groups pKa
Calculations of pI for a compound with more than two
dissociable groups carries more possibility for error
First write out all possible ionic structures for a compound
in order that they occur starting with the most basic to
the most acidic
Next, identify the isoionic, zwiterionic or neutral
representation
- The pI is the pH at the midpoint between the pK
values on either side of the isoionic species
What about peptides or proteins?
The classification of the 20 amino acids is
based on the side chains.
-
You should know for each of the amino acids
-The name and 3 letter designation
- Based on the side chain (R group) if the amino acid
is aliphatic, aromatic, sulfur containing, hydroxyl,
basic, acidic, or an amide derivative
-The charge at high neutral and low pH
- chemical reactivity
- if the amino acid is hydrophobic or hydrophilic,
acidic or basic, polar, uncharged but polar and
charged polar.
- relative size
Peptides & Primary Structure
Protein Functions
– Enzymes -Catalyze a thermodynamically favorable reaction
– Storage/transport - binding proteins fatty acids w/albumin
– no catalytic activity but do form chemical bonds with ligands
– Structure - Several levels
– cytoskeleton, collagen, bone ...
– Receptors
– Growth factors
Amino Acid / protein modification
 Acetylation  Hydroxylation  Phosphorylation  Carboxylation  lipid esterification -
Peptides
When amino acids are linked together it is through
the formation of a peptide bond
The formation of a
peptide bond occurs
by the loss of a water
or dehydration of
water from the a
carboxyl and of one
amino acid and the a
amino of another
amino acid
+H
3N
CH
O
R
C
CH
NH
R
C
O
NH
COOCH
R
Each amino acid is called a residue
Addition of acid or base hydrolyzes the peptide bond and adds water
back across the peptide bond.
The amino (N) terminal is written on the left and the carboxyl (C)
terminal is on the right.
The actual sequence of amino acids is considered the primary structure.
No other factor is considered in this level of structure. Most DNA
mutations have there effect at the primary level.
+H
3N
CH
R
O
R
C
CH
NH
C
O
NH
COOCH
R
Peptide bond
– Rx of bond formation costs energy (ATP) but
degradation of proteins is thermodynamically favorable.
(entropy)
– C-N bond shorter than normal and more like double
bond
– This results in rigid planar, non-rotating links between
aa
– Size of peptides and proteins are described in Daltons
– 1 atomic unit = 1 dalton ; MW = Dalton / kd;
Mr=molecular weight
Many peptides have
important biological
activities
Biologically important peptides
Insulin – Short peptide produced as a
pre-pro-peptide. The
initial peptide is much longer
and is modified twice, each
time a set of peptide bonds
are hydrolyzed. The final
shortened version is active.
There are two subunits,
held together by a disulfide
bond.
Oxytocin and Vasopressin


– Start as long precursors in hypothalamus- whose final form
is 9 aa
– differ by 2 residues
oxytocin - uterine contraction during childbirth and milk
production during lactation
vasopressin - alters blood pressure by forcing kidney to retain
water, increasing the volume of blood
Met-enkephalin (opioid peptides)
Substance P
» Naturally produced peptides, bind to receptors, and
reduce pain cause pleasure. Morphine like
» Opposite effect from opioids
» Stimulates perception of pain (protective mechanism)