What is an AA?

What is a proteinogenic AA?

What is a -carbon and what is it bonded to in
an AA?

An AA is a molecule that contains: NH2 (amino) and COOH

(carboxyl).

NH2 and COOH dont have to be bonded to the same C.

Not every AA in the body is specified by a codon in the

genetic code or incorporated into proteins.

Some AAs are specifically modified for specialized roles in

the body.

Proteinogeneic Amino Acid: 20 -AAs encoded by the human

genetic code.
-carbon is the carbon adjacent to the carboxyl carbon.

Bonded to it in -AAs are H, R (side chain), COOH & NH2

AA Stereochemisty

Except for glycine, all AAs are chiral (stereogenic).

most of them optically active.

All chiral AAs used in eukaryotes are L-AAs.

amino will be drawn on left in a Fischer projection

All AAs but cysteine are in an S configuration.

Cysteine, while still an L-AA has an R configuration

because the CH2SH group has priority over COOH.

List for the nonpolar, nonaromatic side chain

AAs:
Structure
Names
3 letter abbreviation
1 letter abbreviation

A
Ala

G
Gly
Smallest.
Achiral.

L
Leu

V
Val

M
Met
One of the two
AAs containing S.

I
Ile
P
Pro
Cyclic AA.
Constrains flexibility limiting
options for placement and
sig. effecting prolines role
in 2 structure.

With methyl
attached,
relatively
nonpolar.

List for the aromatic side chain AAs:

Structure
Names
3 letter abbreviation
1 letter abbreviation

W
Trp
Uncharged.
Largest
aromatic.

F
Phe
Uncharged.
Smallest aromatic.
Relatively non-polar.
Benzyl side chain.
Y
Tyr
Relatively polar

List for the polar side chains side chain AAs:

Structure
Names
3 letter abbreviation
1 letter abbreviation

S
Ser
Highly polar.
Can do HBonding.

N
Asn
Amide (R)
doesnt
gain/loose p+
with changes in
pH.

T
Thr
Highly polar.
Can do HBonding.

Q
Gln
Amide (R)
doesnt
gain/loose p+
with changes in
pH.
C
Cys
Has a thiol (SH) group.
SH bond weaker than OH
prone to oxidation.

List for the negatively charged (acidic) side

chains side chain AAs:
Structure
Names
3 letter abbreviation
1 letter abbreviation

Negative charges at
physiological pH (7.4)

D
Asp

E
Glu

List for the positively charged (basic) side

chains side chain AAs:
Structure
Names
3 letter abbreviation
1 letter abbreviation

+ charge delocalized over 3

N atoms.

R
Arg

K
Lys

H
His
Ring = imidazole
At physiologic pH, one N is protonated.
Acidic conditions, both Ns are
protonated.

Comment on our ability to classify AAs as

hydrophobic or hydrophilic.

Classifying Aas = complex.

ex: tyrosine has both an OH group (hydrophilic) and an

aromatic ring (hydrophobic).

Some clear conclusions:

Long alkyl side chains are strongly hydrophobic

More likely to be found on inside of proteins.

Alanine, isoleucine, leucine, valine & phenylalanine.

AAs with charged side chains are hydrophilic as are the

amides.

Histidine, arginine, lysine, glutamate, asparate,

asparagine and glutamine.

Remaining AAs are neither particularly hydrophilic or

hydrophobic.

What makes Aas amphoteric species?

AAs are amphoteric species because they can either accept a

proton or donate a proton.
Ionizable groups gain protons under acidic conditions and
loose them under basic ones.
pKa is the pH at which, on average, mocs are deprotonated

[HA] = [A]

pH < pKa most of the species will be protonated.

pH > pKa most of the species will be deprotonated.

AAs have at least 2 pKa values.

pKa1 for the COOH, usually 2

pKa2 usually for the NH2, usually 9-10

Describe what happens to a generic AA at pH

of 1.
Describe what happens to a generic AA at pH
of 7.4.
Describe what happens to a generic AA at pH
of 14.

Both the amino and carboxylic group will be protonated (NH3+

and COOH).

Charge will be positive because the amino group is

positively charged and the carboxylic group is neutrally
charged.

The carboxylic group will be deprotonated (COO) and the

amino group with be protonated (NH3+ ).

The ensuing molecule has a + and charge an overall is

electrical neutral. We call such molecules dipolar ions or
zwitterions.

Zwitterions exist in water as internal salts.

Both the amino and carboxylic group will be deprotonated (NH2

and COO).

Assuming that the titration of each proton

occurs as a distinct step, resembling two
combined monoprotoic acids, what would
the titration curve look like for a generic AA
with an uncharged side chain look like?

In a 1 M solution of the base:

When 0.5 equivalents of base have been
added, [ ]of fully protonated AA and its
zwitterion are equal. The pH = pKa1.
When pH is close to its pKa value of a solute,
a solutions acting as a buffer.
Adding 1.0 equivalent base, the AA exists
solely as a zwitterion. At this point, the
pH = the isoelectric point (pI) the point
the moc is electrically neutral.
At the neutral point, the moc is especially
sensitive to pH changes.
At 1.5 equivalents of base added, the [ ] of
the zwitterion = the fully deprotonated
form and the pH = pKa2.
At 2.0 equivalents of base, the AA is fully

How do you calculate the pI for a neutral AA?

How do you calculate the pI for an acidic AA?
How do you calculate the pI for a basic AA?
Comment on the relative pI values for AAs with
acidic vs. basic side chains.

Amino acids with acidic side chains have pI values well below
6.
Amino acids with basic side chains have pI values well above
6.

Describe peptide bond formation.

Example of a condensation/dehydration reaction or an acyl substitution

reaction.
1. Nucleophilic amino
group attacks the
electrophilic carbonyl
group.
2. After the attack, the
hydroxyl group of the
carboxylic acid is
kicked off.

N-te
rmin
us

Note: By convention peptides

are drawn and read from N to
C terminus.

C-

nu
mi
r
e
t

Amide has delocalizable

e- in the carbonyl and
lone pair on the amino N
= resonance.
CN bond has partial
double bond character,
restricting rotation and
making the backbone
more rigid.

Describe bond hydrolysis.

For enzymes to carry out their function, peptides need to be

relatively stable in solution. Thus, they dont typically fall
apart on their own.
On the other hand, to digest proteins, we need to break them
down.

Chemically speaking, amides can be hydrolyzed using acid

or base catalysts .

This is called acid hydrolysis.

Non-specific way of cleaving.

In living organisms, hydrolysis is catalyzed by hydrolytic

enzymes that cleave at specific points in peptide chains

This is called proteolysis.

Specific way of cleaving.

Examples: trypsin & chymotrypsin.

These break the amide bond by addition a H to the

What is a protein and what are its general

functions in the body.
What are the levels of protein structure?
What exactly is the 1 structure of a protein?

Proteins are polypeptides ranging from a few to thousands of

AAs.

They can act as: enzymes, hormones, membrane pores,

membrane receptors, cell structure elements.

Levels of structure: Primary, Secondary, Tertiary & Quaternary.

Primary structure: the linear arrangement of AAs coded in an
organisms DNA.

Stabilized by the formation of covalent peptide bonds

between AAs.

Encodes all info needed for folding all higher levels of

structure (the protein adopts the most energetically
favourable arrangement in a given environment).

Can be determined with the lab technique sequencing

Describe a proteins 2 structure.

Describe alpha helices.

2 structure: the local structure of neighboring AAs.

Primarily the result of H-bonding between nearby AAs.
Two most common structure are -helices & -pleated sheets.

Key to their stability is the formation of intramolecular Hbonds between different residues.

-helices

Rod-like peptide chain coiling clockwise around a central

axis.

Stabilized by H bonds between carbonyl O and an amide H

four residues down the chain.

Side chains point outwards.

Important component of keratin (a fibrous structural

protein).

Describe -pleated sheets.

Describe the role of proline.

Peptide chains lie alongside each other either parallel or antiparallel and are held together by H-bonds.
Bonds are between carbonyl O and amide H on an adjacent
chain.
Assume pleated/rippled shape to accommodate as many Hbonds as possible.
R groups point above/below plane of the sheet.
Proline introduces a kink in the peptide chain when found in
the middle of an -helix due to its rigid cyclic structure

Rarely found in -helix except in helices that cross the cell

membrane.

Found as the residue at the start of a -helix.

Rarely found in the middle of pleated sheets.

What are the two broad division of proteins

based on 3 & 4 structure?
What causes 3 & 4 structure?
Comment on the chronology of protein
formation.

Broad division:

Fibrous proteins that have structures that resemble

sheets/long strands.

Globular proteins that tend to be spherical.

Protein folding causes 3 & 4 structure.

Likely that 1, then 2 structures form first then hydrophobic
interactions and H-bonds case the protein to collapse.
Intermediate states are known as molten globules.
Process is very fast (much less than a second).

Describe tertiary structure.

Tertiary structure is a proteins 3-D shape.

Mostly determined by hydrophobic and hydrophilic
interactions between R groups.

Hydrophobic residues hangout inside the peptide.

N-H and C=O bonds in the peptide tend to be pulled to

the inside by these hydrophobic residues, H-bonding and
engaging in electrostatic interactions to further stabilize
the protein.

3-D structure can also be determined by H-bonding & acidbase interactions (salt bridges).
Disulfide bonds when two cysteine residues oxidize to form
cystine (loosing two protons and two electrons), creating a
loop in the protein structure.
The loss of tertiary structure is called denaturation and
results in loss of function.

Explain why from an energy standpoint,

hydrophobic residues hide in the centre of
proteins.

When solutes dissolve in solvent, solvent mocs form a

solvation layer around the solute.
Hydrophobic Rs in aqueous solutions cause the solvation layer
not to be able to form H-bonds with it, forcing the H2O to
rearrange itself (meaning negative entropy, -S).

This makes the overall process nonspontaneous (G > 0).

Putting hydrophilic residues on the exterior allows H2O mocs

more latitude increasing their entropy (S > 0).

This makes the overall process spontaneous.

Also allows the protein to achieve max stability.

Describe quaternary structure.

4 structure: an aggregate of smaller globular peptides or subunits creating

the functional form of the protein.
Unlike the other levels, not all proteins have this type of structure.
Requires more than one polypeptide chain.
Example: hemoglobin
Has 4 subunits, each binding to one moc of O 2 subunits and 2
subunits.
Example: immunoglobin G (IgG)
Has 4 subunits.
Uses all types of bonds: van der Waals, H-bonds, ionic bonds, covalent
bonds.
Roles served:
1. Become more stable by reducing surface area of protein complex.
2. Reduce amount of DNA needed to encode the protein complex.
3. Bring catalytic sites close together allowing intermediate from on
reactions to be shuttled off to a second one.
4. Can induce cooperativity or allosteric effects one subunit

Describe conjugated proteins.

Conjugated proteins: proteins that derive part of their function

from covalently attached mocs called prosthetic groups
(organic mocs, metal ions).

Lipid prosthetic group lipoprotein.

Carbohydrate prosthetic group glycoprotein.

Nucleic acid prosthetic group nucleoprotein.

Example: hemoglobin subunits contain the prosthetic group

heme.

Heme contains an iron atom at its core, binds and carries

O.

Hemoglobin inactive without this group.

Prosthetic groups can direct a protein to be delivered to a

Describe the denaturation of proteins.

Denaturation: protein loses its 3-D structure.

Often irreversible.
Unfolded proteins cant catalyze reactions.
Two main causes:

Heat kinetic energy may overcome hydrophobic

interactions holding a protein together.

Solutes interferes directly with the forces that hold

proteins together 2, 3 & 4).