Chapter 5 Amino acids and Proteins

Part I
Trn Th Minh c

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What are amino acids and proteins?

Amino acids = building blocks of proteins

Proteins = biological macromolecules, products

of gene transcription and translation.

Proteins contains 1 long chains of amino acid

residues.

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 Chemical composition of proteins

Element Proteins Carbohydrates Nucleic acids

C 50 55% 25%
H 6.5 7.3% 50%
O 21 24% 25%
N 15 18%
S 0 24%
P Very little 8 10%
Others Fe, Zn, Cu, Mn, Ca, etc

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 Sources of proteins
Source Protein (%)
Liver 18 19
Heart 16 18
Dairy, meat and Muscle meat from livestock 16 22
poultry
Eggs (chicken, duck, quail) 13 15
Cow Milk 35
Fish 17 21
Shrimp 19 23
Seafood Squid 17 20
Snail 11 12
Clam 89
Soy 34 40
Nuts and Peanuts and beans 23 27
Veggetable Corn 8 10
Rice General Biochemistry 1 78 4
Structures and Properties of Amino Acids

There are 20 common amino acids

Amino acids contain a central tetrahedral C

Amino acid has an NH2 and COOH group and a

side chain R attached to the central C

Amino acids can join via peptide bonds

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 Structures and Properties of Amino Acids

Anatomy of an amino acid. Except for proline and its

derivatives, all of the amino acids commonly found in
proteins possess this type of structure.

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 Structures and Properties of Amino Acids

Two amino acids

can react with
loss of a water
molecule to form
a covalent bond.
The bond joining
the two amino
acids is called a
peptide bond.

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20 common
amino acids

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The 20 Common Amino Acids
You should know names, structures, pKa values,
3-letter and 1-letter codes

1. Nonpolar Aliphatic amino acids

2. Aromatic amino acids
3. Polar, uncharged amino acids
4. Acidic amino acids
5. Basic amino acids

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Nonpolar (hydrophobic) amino acids.

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Nonpolar (hydrophobic) amino acids

Some of the.
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Aromatic amino acids

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Polar, uncharged amino acids

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Polar, uncharged amino acids

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Acidic (negatively charged) amino acids

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Basic (positively charged) amino acids

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 Essential amino acids

Most documents list 8 essential amino acids:

Val, Leu, Ile, Met, Thr, Phe, Trp and Lys

Some list: Arg, His, Cys as essential amino

acids as well

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 Several Amino Acids Occur Rarely in Proteins

Selenocysteine in many organisms

Pyrrolysine in several archaeal species
Hydroxylysine, hydroxyproline - collagen
Carboxyglutamate - blood-clotting proteins
Pyroglutamate in bacteriorhodopsin
Phosphorylated amino acids a signaling device

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Several Amino Acids Occur Rarely in Proteins

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 Several Amino Acids Occur Rarely in Proteins

Some amino acids are less common, but nevertheless found in

certain proteins. Hydroxylysine and hydroxyproline are found in
connective-tissue proteins; carboxy-glutamate is found in blood-
clotting proteins; pyroglutamate is found in bacteriorhodopsin
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 Several Amino Acids Do Not Occur in Proteins, But Play
Other Roles in Nature

Several amino acid derivatives that act as neurotransmitters

and hormones.

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 Acid-Base Properties of Amino Acids

The ionic forms of the amino acids, shown without

consideration of any ionizations on the side chain.
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 Acid-Base Properties of Amino Acids

Amino Acids are Weak Polyprotic Acids

The degree of dissociation depends on the pH of
the medium
For amino acids which do not have a dissociable
side chain, the first dissociation is that of the -
carboxyl group:
H2A+ + H2O HA0 + H3O+
0
[HA ][H O ]
K a1
3
[H A ] 2
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 Acid-Base Properties of Amino Acids

For amino acids which do not have a dissociable side

chain, the second dissociation is that of the -
amino group:

HA0 + H2O A + H3O+

[A ][H O ]
K a2 3
0
[HA ]
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pKa Values of the Amino Acids

You should know these numbers and know what

they mean
Alpha carboxyl group: pKa = 2
Alpha amino group: pKa = 9
These numbers are approximate, but entirely
suitable for our purposes.
At physiological pH (~7.4), -COOH completely
dissociates while -NH3+ has not begun

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 -COOH and -NH3+

Dissociation constant of -COOH and -NH3+

are affect by each other
pKa of COOH is 2.0 2.1 < pKa of CH3COOH
(4.76)

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4.2 What Are Acid-Base Properties of Amino Acids?

27
Acid-Base Properties of Amino Acids

28
 pKa Values of the Amino Acids
You should know the pK values for these R groups
and what they mean

Arginine, Arg, R: pKa(guanidino group) = 12.5

Aspartic Acid, Asp, D: pKa (carboxyl) = 3.9
Cysteine, Cys, C: pKa (sulfhydryl) = 8.3
Glutamic Acid, Glu, E: pKa (carboxyl) = 4.3
Histidine, His, H: pKa (imidazole) = 6.0

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pKa Values of the Amino Acids

You should know the pK values of these R groups

and what they mean

Lysine, Lys, K: pKa (amino) = 10.5

Serine, Ser, S: pKa (hydroxyl) = 13
Threonine, Thr, T: pKa (hydroxyl) = 13
Tyrosine, Tyr, Y: pKa (phenolic OH) = 10.1

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 Titrations of polyprotic amino acids

Figure 4.7 Titration of

glutamic acid

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 Titrations of polyprotic amino acids

Titration of lysine.

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 Some equations

pI = (pKa1 + pKa2)/2

Henderson-Hasselbalch equation

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 A Sample Calculation
What is the pH of a glutamic acid solution
if the -carboxyl is 1/4 dissociated?
[1]
pH = 2 + log10
[3]
pH = 2 + (0.477)
pH = 1.523

Note that, when the group is dissociated, is

dissociated and is not; thus the ratio in the log
term is over or .

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Another Sample Calculation
What is the pH of a lysine solution if the side
chain amino group is 3/4 dissociated?

[3]
pH = 10.5 + log10
pH = 10.5 + (0.477)
[1]
pH = 10.977 = 11.0

Note that, when the group is dissociated, is

dissociated and is not; thus the ratio in the log term is
over or 3/1.
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 Reactions of Amino Acids
Carboxyl groups form amides & esters
Amino groups form Schiff bases and amides
Edman reagent (phenylisothiocyanate) reacts
with the -amino group of an amino acid or
peptide to produce a phenylthiohydantoin
(PTH) derivative.
Side chains show unique reactivities
Cys residues can form disulfides and can be
easily alkylated
Few reactions are specific to a single kind of
side chain

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Carboxyl group reactions

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Amino group reactions

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 Reactions of Amino Acids

Ninhydrin Reaction
is characteristic of
amino acids

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 Reactions of Amino Acids

Edmans reagent reacts with the N-terminal amino acid of a

peptide or protein to form a cyclic thiazoline derivative that
reacts in weak aqueous acid to yield a PTH-amino acid.
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 Reactions of Amino Acids

Cysteine residues react with each other to form disulfides. This

reaction is an oxidation-reduction reaction.
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Stereochemistry of Amino Acids
All but glycine are chiral
L-amino acids predominate in nature
D,L-nomenclature is based on D- and L-
glyceraldehyde
R,S-nomenclature system is superior, since
amino acids like isoleucine and threonine
(with two chiral centers) can be named
unambiguously

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Stereochemistry of Amino Acids

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 Discovery of Optically Active Molecules and
Determination of Absolute Configuration

Emil Fischer deduced the

structure of glucose in
1891. Fischers proposed
structure was confirmed by
J. M. Bijvoet in 1951 (by X-
ray diffraction).

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 Fischer Projection

C chain is depicted vertically

Other bonds horizontally

C is at the center of the crossing line

Carbonyl C is ALWAYS on the top

Aldose (C1 = -CHO), Ketose (C2 = -C=O)

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 4 steps to determine R, S

1. Rank atoms about the C* by atomic number

2. Ensure number 4 is in the back
3. Cross out number 4
4. Trace an arc from 1 2 3

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Rules for Description of Chiral Centers in the (R,S)
System

Naming a chiral center in the (R,S) system is accomplished by

viewing the molecule from the chiral center to the atom with
the lowest priority. The priorities of the functional groups are:
SH > OH > NH2 > COOH > CHO > CH2OH > CH3
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 Spectroscopic Properties

All amino acids absorb at infrared wavelengths

Only Phe, Tyr, and Trp absorb UV
Absorbance at 280 nm is a good diagnostic
test for amino acids

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 Spectroscopic Properties

The UV spectra
of the aromatic
amino acids at
pH 6.

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 Fundamental Structural Pattern in Proteins

Proteins are unbranched polymers

Amino acids join head-to-tail forming peptide bonds
Peptide bond formation results in release of 1 H2O
The peptide backbone of a protein consists of the
repeated sequence N-C-Co-
N is the amide N of the amino acid
C is the alpha-C of the amino acid
Co is the carbonyl carbon of the amino acid

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 Fundamental Structural Pattern in Proteins

Peptide formation is the creation of an amide bond

between the carboxyl group of one amino acid and the
amino group of another amino acid.

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 The Peptide Bond

is usually found in the trans conformation

has partial (40%) double bond character
N partially positive; O partially negative
has a length of about 0.133 nm - shorter than a
typical single bond but longer than a double
bond

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 Peptides

Short polymers of amino acids

Each amino acid unit is called a residue
2 residues - dipeptide
3 residues - tripeptide
12-20 residues - oligopeptide
many - polypeptide

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 Protein
One or more polypeptide chains

One polypeptide chain - a monomeric protein

More than one - multimeric protein
Homomultimer - one kind of chain
Heteromultimer - two or more different chains
Hemoglobin, for example, is a heterotetramer
It has two alpha chains and two beta chains

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Proteins - Large and Small

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Proteins - Large and Small

Molecular weights:
Insulin, 5,733
Cytochrome c, 12,500
Ribonuclease, 12,640
Lysozyme, 13,930
Myoglobin, 16,980

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 Proteins - Large and Small

Molecular weights: Hemoglobin, 64,500;

Immunoglobulin, 149,900;
Glutamine synthetase, 600,000.

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 The Sequence of Amino Acids in a Protein

Is a unique characteristic of every protein

Is encoded by the nucleotide sequence of DNA
Is thus a form of genetic information
Is read from the amino (N) terminus to the
carboxyl (C) terminus

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 HOMEWORK
The following tasks should be confined in 1 page:
1. Write a 1 A4 page review of all 20 amino acids.
2. Draw their chemical structures: by hand or by computer.
Use color code mentioned in class.
3. Divide them into groups as discussed in class.
4. Mark chiral centers by asterisks.
5. Draw a peptides chemical structure with a sequence of
your choice (at least 3 aa). Highlight the peptide bond.
6. If you would like to obtain a computer program for
drawing chemical structures, contact me at
ttmduc@hcmiu.edu.vn

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