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Amino Acids
Biochem 4511
Figures: Essentials of Biochemistry, 3rd Ed
...
, Moran et al
...
, Nelson & Cox
Fundamentals of Biochemistry 2nd Ed
...


Variable
Group

Amine

Greek Lettering

 Alpha
 Beta
 Gamma
 Delta
 Epsilon


Zeta

Amino acids are Chiral Molecules
• A molecule that cannot be superimposed on its mirror
image is chiral

Amino Acids are Chiral

• All amino acids except for glycine are chiral
• All proteogenic amino acids are L-stereoisomers
•

L/D

system is historical in origin (unlike S/R system)

Optical Rotation of Glyceraldehyde
• Chiral molecules are optically active and rotate
plane polarized light
• The L/D nomenclature is based on the structure of
L-glyceraldehyde

Levorotatory, “left”, (-), L

Dextrorotatory, “right”, (+), D

Amino Acid Stereochemistry
• Most naturally occurring amino acids have L-stereochemistry
•

D-α-amino

acids do exist in nature (not in translated proteins)
but are less abundant and found in bacterial cell walls and
natural products (including antibiotics)

Fischer Projections
• Fischer projections are a convenient way of presenting
three-dimensional chemical structures in two-dimensions
• Pioneered by Emil Fischer

• Horizontal groups project above the page
• Vertical groups project behind the page

L
L-alanine,

Ala, A

+H N
3

COO-

+H

COO-

3N

and D Isomers
D-alanine,

ala, a

+H N
3

COO-

+H

COO-

3N

Use these projections for consistence and simplicity
...
5

• Carboxyl group: pKa ~ 2
• Several side chains are ionizable
with variable pKa
• At physiological pH (7
...
4 is zero – Zwitterion

Zwitterions
pK1

pK2

pK values of free vs protein
incorporated amino acid
side chains

In free a
...


Within proteins

Titrating Alanine

• Alanine is amphoteric - it can act as an acid or base

20 “Common” or “Natural” AAs

20 “Common” or “Natural” AAs
A Ala Alanine

F Phe Phenylalanine

K Lys Lysine

P Pro Proline

T Thr Threonine

Q Gln Glutamine

V Val Valine

C Cys Cysteine

G Gly Glycine

L Leu Leucine

D Asp Aspartate

H His Histidine

M Met Methionine

R Arg Arginine

W Trp Tryptophan

N Asn Asparagine

S Ser Serine

Y Tyr Tyrosine

E Glu Glutamate

I Ile Isoleucine

+H N
3

COO-

Naming the Amino Acids

• Asparagine was the first amino acid isolated, from asparagus
(1813), but it was not confirmed as an amino acid until 1932

Small Nonpolar

Large Nonpolar (Hydrophobic)

Methionione
• In contrast to other hydrophobic
a
...
, Methionine is rather flexible
...

• Methionines are also easily (and
reversibly) oxidized and
therefore are believed to protect
other amino acids against
oxidation
...
5

Phenylketonuria (PKU)
• Genetic disorder characterized by a mutation in the gene for
the hepatic enzyme phenylalanine hydroxylase (PAH)
...

• Treatment: strict PHE-restricted life-long diet supplemented
by amino acids and other nutrients
...


PAH

Phenyl pyruvate
(detected in urine)

Tryptophan

Tryptophan
(Trp, W)

Serotonin
(5-hydroxy tryptamine)

•Precursor of Serotonin – neurotransmitter = “happiness hormone”
...

•Some psychedelics are agonists of this molecule
...

• [Protein] can be
determined based
on detection of
Tyr/Trp in proteins!
•Both residues are also FLUORESCENT
...


Practical Application: UV Spectra

• Beer-Lambert Law (Beer’s Law)
Absorbance = εcℓ
ε = “extinction coefficient” of molecule

20 “Common” or “Natural” AAs

Uncharged and Polar

OH

+

H3N

COO-

Cysteine Ionization

Free a
...
pKa = 8
...
8±2
...
g
...
Straight Hair

Uncharged and Polar

H2N

O

O

NH2
+

H3N

COO-

+

H3N

COO-

Charged Side Chains: Carboxylic Acids

O
NH2
+

H3N

COO-

Asparagine
(Asn, N)

•Glutamate plays important role in a
...
metabolism – transamination
reactions
•Monosodium Glutamate is commonly used as a taste enhancer
...
9
Glu pKa = 4
...
5

pKa 12
...
5

Arginine

Arginine
Arg (R)
pKa 12
...
0

Histidine: pKa 6
...
6±1 in proteins

What % of the histidine side chain is ionized at pH 7?
[A-]
= 10pH-pKa = 10(7-6) = 10
[HA]

@ pH 7
...
0/6
...
5
Terminal amine: ~9
...
7
Asp & Glu: 4
His: 6/6
...
4/6
...
5
Arg: 12
...
a
...

Selenocysteine has both a lower pKa (5
...
These properties make it very
suitable in proteins that are involved in antioxidant activity
...

Michael Chan and
Dr
...

(Figures from Chan lab web page)

• Pyrrolysine is encoded in Archaea by another “stop” codonUGA
...
a
...


Post-translationally
Modified Amino Acids

Phosphorylation
(pTyr, pSer, pThr)

Acetylation
(Lys)

Methylation 4-hydroxyproline
(Lys, Arg)

MEMORIZE Your Amino Acids
Names
...
Structures
...

• What are the nonpolar amino acids?
• What are the ionizable amino acids?
• At any given pH, what is the predominant ionization state?
• Which amino acids have planar side chains?
• Which amino acids have β-branching?
• Which amino acids have 2 chiral centers? No chiral centers?
What other properties can you think of to categorize amino
acids?

Problems:
1,3,4,5,6,7,8,10,11

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