Chapter 3

A M IN O A C ID S A N D
P R O TEIN S

Am ino Acids
Have a wide variety of biological

roles
determined
by
their
characteristic chemical feature
Common amino acids can be
grouped (chemical features)
There are 20 common amino acids

Roles ofAm ino Acids

They may be polymerized to form peptides,

most notably proteins (polypeptides)

They serve as precursors for other small

biomolecules (e.g. Purines, pyrimidines,

poryphyrins).
They may be oxidized to serve as an

energy source (fuel) for the cell.

G eneralFeatures for Am ino Acids

Contains tw o characteristic FUN CTIO N AL G RO UP an
am ino group and a carboxylic acid group.
For amino acids used in proteins, these are

attached to a central carbon atom, C, the

alpha carbon, to which are also attached a
hydrogen atom and an organic side chain group
R.

 The central carbon is a chiral center

for 19 of the 20 common amino acids,

and
by
far
the
common
stereoisomeric form is the L
isomer.
Glycine has as its side chain a simple
hydrogen atom, so it is not chiral
(achiral). Proline has its side chain
fused to the -amino group, but it still
has an asymmetric center in the carbon.

G eneralfeatures ofAm ino Acids (cont.)

D isomers of amino acids are found only

rarely for example, in bacterial cell walls

and some short antibiotic peptides.

Stereochemistry of the 2 optical isomers of the common amino

acids.

Som e other im portant features ofam ino acids

Characteristically

isolated

as

white

crystalline ionic solids with high melting

points and poor solubility in organic
solvents (they are moderately soluble in
water)
Amino acids dissolve in water as dipolar ions,

or zwitterions, due to ionization of the acid

and amino groups

Ionization of Amino Acids

Remember, amino acids without charged groups on side
chain exist in neutral solution as zwitterion with no net
charge

Som e other im portant features ofam ino acids

The -carboxyl group typically has a

pKa around 2.0 2.4 and the -amino

group typically has a pKa around 9.0
9.7.

Titrable groups on the side chains vary

considerably in their pKa values.

Points to note:
At acid pH, glycine is found mainly in the form of the

cation; at alkaline pH, glycine is mainly in the form of the

anion.
At physiological pH, around pH 7, glycine exist mainly as

the zwitterion, and only small amounts of the electrically

neutral, cationic, or anionic species present.
At pH 6.1, there are equal (and relatively small) numbers

of cations and anions, and the dominant species is the

zwitterion.

The 20 Com m on Am ino Acids

Amino Acid

Three-Letter

Single Letter

Alanine

Ala

Arginine

Arg

Aspargine

Asn

Aspartic Acid

Cys

Cysteine

Glu

Glutamic acid

Glu

Glutamine

Gln

Glycine

Gly

Histidine

His

Isoleucine

Ile

Leucine

Leu

Lysine

Lys

The 20 Com m on Am ino Acids

Amino Acid

Three-Letter

Single Letter

Methionine

Met

Phenylaline

Phe

Proline

Pro

Serine

Ser

Threonine

Thr

Tryptophan

Trp

Tyrosine

Tyr

Valine

Val

Classifi
cation ofAm ino acids
Amino acids are classified according to two major

criteria: the polarity of the side chains and the

presence of an acidic or basic group in the side chain.

Four groups of amino acids are found in proteins:

first, those with nonpolar side chains; second, those

with electrically neutral polar side chains; third, those
with carboxyl groups in their side chains; fourth,
those with basic side chains.

The 9 N ine Classes ofAm ino Acids

Clas
s

Members

Properties

Gly

Ala, Val, Leu, polar

Ile

Aliphatic side chains; bulky and nonpolar

Pro

Side-chain loop connecting -carbon and

4
5

Simple hydrogen atom side chain; non

-amino group; nonpolar and rigid

Phe, Tyr, Trp

Aromatic side chains; bulky, nonpolar

Cys, Met

Sulfur-containing nonpolar side chains;

reactive thiol on Cys

Ser, Thr

Alcohols; hydrophilic and reactive hydroxyl

groups

Glu, Asp

Carboxylic acids; anionic

Gln, Asn

Amides of carboxylic acids; polar, bulky

His, Lys, Arg

Basic side chains; cations Lys and Arg, but

G roup 1 (N onpolar side chains)

Glycine - C-H bond
Alanine aliphatic hydrocarbon
Valine - aliphatic hydrocarbon
Leucine - aliphatic hydrocarbon
Isoleucine - aliphatic hydrocarbon
Proline aliphatic cyclic structure/ imino acid
Phenylaline aromatic hydrocarbon
Tryptophan idole rings
Methionine sulfur atom, aliphatic hydrocarbon

G roup 2 (N eutralpolar side chains)

Serine - polar group (-OH) bonded to aliphatic

hydrocarbons
Tyrosine - polar group (-OH) bonded to aromatic

hydrocarbons
Threonine - polar group (-OH) bonded to aliphatic

hydrocarbons
Cysteine - polar side chain consists of a thiol group

(SH)
Glutamine & Asparagine amide groups, which

are derived from carboxyl groups, in their side chains

G roup 3 (Acidic side chains)

Aspartic acid & Glutamic acid contains

carboxyl groups in their side chains in addition

to the one present.
side chain of each of these two amino acids is
negatively charged at neutral pH.

G roup 4 (Basic side chains)

side chain in all three is positively charged at or
near neutral pH.
Histidine - can be found in the protonated or
unprotonated forms in proteins, and the
properties of many proteins depend on whether
individual histidine residues are or are not
charged
Lysine - the side-chain amino group is attached
to an aliphatic hydrocarbon tail
Arginine - guanidino group, is more complex in
structure than the amino group, but it is also
bonded to an aliphatic hydrocarbon tail

The potential for ionization of other

side chains can be quite important in
biological function.
The phenolic group on Tyr is a weak

acid and can be ionized to form a

phenolate ion at pH values not so far
from physiological, and its acid-base
behavior may be important in catalytic
mechanisms of some enzymes.

 The thiol group on the side chain of Cys is a weak acid

and may also be ionized at a pH close to physiological;

again, this can be important for acid-base behavior in
certain enzyme catalytic mechanisms.

The imidazole ring of His can accept or donate protons

at pH values near neutral; this is an important factor in

acid-base catalysis in many enzymes.

 When

the

polymerized

amino
into

acids

are

polypeptide

protein, the -carboxyl and -amino

groups

are

joined

in

AMIDE

LINKAGES and are effectively neutral

as

far

as

concerned.

acid-base

behavior

is

Cysteine
Notable for its ability to form disulfide

bonds with adjacent thiols, especially Cys-toCys disulfide bridges,

which are often

important in stabilizing the folded tertiary

structure of protein.
Bridge formation requires oxidation of the

thiols

on

both

requires reduction.

participants;

disruption

Som e Im portant but Less Com m on Am ino

Acids
Hydroxyproline & Hydroxylysine
Found in connective tissue protein collagen.
Extra hydroxyl group on these amino acids

is a major factor in stabilizing collagens

characteristic left-handed helical
conformation.

Som e Im portant but Less Com m on Am ino

Acids

Selenocysteine
Appears in a few proteins, such as

glutathione peroxidase.
Resembles Cys in structure, albeit with a

selenium atom replacing the sulfur atom

in the side chain.

Som e Im portant but Less Com m on Am ino

Acids
Ornithine
Similar to Lys, with an amino group at the end of

its side chain.

An important player in the urea cycle.
Precursor to arginine and to certain polyamines

such as spermidine and spermine.

Som e Im portant but Less Com m on Am ino

Acids

Citrulline
Derived from carbamoylation of

orthinine on the side chain.

An important player in the urea cycle.

Som e Im portant but Less Com m on Am ino

Acids

Homocysteine
An intermediate in the catabolism of

methionine, and it is closely connected

to the functioning of the methyl-donor
compound, S-adenosylmethionine.

Som e Im portant but Less Com m on Am ino

Acids
Gamma-Aminobutyric acid (GABA)
An important neurochemical that inhibits neuronal

action by binding to specific receptors (GABA

receptors) both pre-and post-synaptically.
Glycine & glutamate are also neurotransmitters.
Glycine - inhibit neurotransmission
Glutamate- excite neuronal action

Polypeptides and Protein

Prim ary Structure
Peptide Bonds joins two amino

acids.
Polypeptide a string of amino acids

joined together by peptide bonds.

Oligopeptides shorted chains of

amino acids

Peptide Bonds
Are amide linkages formed by the

condensation of the -carboxyl group

of one amino acid with the -amino
group of another amino acid

 N-terminus
One end of the chain with free

amino group

C-terminus
One end of the chain with free

carboxylic acid group

 By convention, a polypeptides

sequence of amino acids is written

starting with the N-terminus on the
left and the C-terminus on the right.

PRO TEIN CLASSIFICATIO N

Classified by their structure:

GLOBULAR and FIBROUS.

G lobular Proteins
Have

overall

spherical shape

and

are

usually folded into a compact mass.

Some are soluble in the aqueous cytosol,

whereas others are embedded or otherwise

closely associated with biomembranes.
Examples:

albumin

antibodies,

many

enzymes,

Fibrous Proteins
Tend to have an extended

conformation, not spherical

Generally much less water soluble
than globular proteins. Because of
this lack of aqueous solubility,
fibrous proteins are often found as
aggregate

PRO TEIN S m ay also be classifi

ed according
to their biologicalfunction.
Mechanical support and cushioning:

collagen and elastin

Mechanical work: actin, myosin, tubulin
Catalysis: enzymes such as ribonuclease,
hexokinase, DNA polymerase
Transport and Storage: hemoglobin,
myoglobin, serum albumin
Communication and defense: antibodies,
peptide hormones, hormone and
neurotransmitter

Protein Structure
Many different conformations are

possible for proteins:

Due to flexibility of amino acids linked by

peptide bonds

At least one major conformation has

biological activity, and hence is
considered the proteins native
conformations.

Levels ofProtein Structure

PRIMARY structure: the SEQUENCE of amino acids
in a polypeptide chain, read from the N-terminal
end to the C-terminal end
SECONDARY structure: the SPATIAL arrangements
(conformations) in localized regions of a
polypeptide chain; refers only to interactions of
the peptide backbone e. g., -helix and -pleated
sheet
TERTIARY structure: 3-D arrangement of all atoms
QUATERNARY structure: arrangement of
monomer subunits with respect to each other

1 Structure
The 1 sequence of proteins determines its

3-D conformation
Changes in just one amino acid in sequence
can alter biological function, e.g.
hemoglobin associated with sickle-cell
anemia
Determination of the sequence involves
cleaving the protein to smaller peptides,
determining the sequence of the individual
peptides, and combining the peptide
sequences to obtain that of the protein

Prim ary Structure

Secondary Structure
Refers to a regular spatial

arrangement of the atoms along the

chain backbone.
Stabilized by weak, noncovalent
interactions such as: hydrogen
bonds, hydrophobic interactions, and
electrostatic attractions.
2 principal secondary structures:
-helix
-sheet

-helix
Formed

from
polypeptide.

single strand

of

Stabilized by a characteristic pattern

of hydrogen bonding of the carbonyl

of one amide to the NH of another
amide, four residues farther along
the chain.

-helix
The side chain of the

amino
acids
are
exposed and project
laterally away from
axis of the helix.
Ala and other nonpolar,
bulky
side
chains amino acids
have a high tendency
to adopt the -helical
conformation.

-sheet
Formed from two or more strands of

amino acids.
The strands are extended, and there
is roughly coplanar alignment of
backbone atoms across the strands.
-sheet uses hydrogen bonding
between backbone carbonyl and
amino groups on the strands.
(Hydrogen
bonding
across
the
strands)

-sheet