BIOC1600

Amino Acids

Brian Wong
bcwwong@hku.hk
Learning objectives
• Describe the general structure of amino acids
• Classify amino acids according to physicochemical
properties of side chains
• Describe biological roles of amino acids
• Differentiate between the L- and D-isomers of
amino acids
Proteins are polymers of amino acids

α α α α

Backbone
Amino acids
An amino acid is a molecule that contains both amino
and carboxyl functional groups.

COO- COO- COO- COO-

+H N C
αCH2 3 α H H αC H H αC H

β CH2 R +H N C
3 β
H H βC H
+H N C
γ CH2 R 3 γ H

δ
CH2 R

ε CH3
α-amino acid β-amino acid γ-amino acid

Greek nomenclature for amino acids: carbons atoms are assigned according to
sequences in the Greek alphabet. The carbon next to the carboxyl group is the
alpha carbon.
α-Amino acids are used in protein biosynthesis.
 General structural formula for
α-amino acid
COO- carboxyl group COOH
amino H N+ C H H2N C H
group 3
R α-carbon R
Side-chain group
(20 different R groups)

Ionized form, Zwitterion Unionized from

• Predominate at neutral pH
• Amino group protonated
• Carboxyl group deprotonated
20 standard amino acids
Properties of amino
acids determined by
the side-chain group

3-letter and 1-letter code

20 standard amino acids
20 standard amino acids
Essential vs non-essential amino
acids
Essential amino acids –
cannot be synthesized
and must be obtained in
the diet
Conversion of L-phenylalanine to L-tyrosine catalyzed by
phenylalanine hydroxylase

www.sciencedirect.com
21st amino acid - Selenocysteine
• Selenocysteine (21st standard amino acid)
• Sec or U
• Discovered in 1986
• Present in proteins from bacteria, archaea,
and eukaryotes
• Synthesized from serine linked to a specific
tRNA that recognizes the UGA stop codon
• Found in glutathione peroxidase (prevent
oxidative damage)
• see doi: 10.1111/j.1365-2958.1991.tb00722.x.
Q: How would you determine experimentally that
selenocysteine is derived from serine instead of cysteine?
22nd amino acid - pyrrolysine
• Pyrrolysine (22nd standard amino acid)
• Pyl or O
• Discovered in 2002 (Science 296:1462-1466)
• Found in some methanogenic archaea and
bacterium; not present in human
• Converted from lysine
• L-pyrrolysine is attached to tRNA as a free
molecule by specific aminoacyl-tRNA
synthetase
Some examples of posttranslational modification of proteins
Non-proteinogenic amino acids

Citrulline ornithine

and more …

Q: Are citrulline and ornithine α-Amino acids?

Beta amino acids

β-alanine
Beta-alanine, from breakdown products of
pyrimidines

Carnosine serves as a buffer against lactic acid, reducing the acidity in muscles
during high-intensity exercise.
Nutrition and Enhanced Sports Performance, Second Edition
https://doi.org/10.1016/B978-0-12-813922-6.00028-X
Gamma amino acid
• e.g. GABA from decarboxylation of glutamate

α β γ

• Both glutamate and GABA are neurotransmitters

• Glutamate generated from glutamine
Uncommon amino acids in proteins

From modifications of
standard amino acids after
protein synthesis (protein
post-translational
modifications) – essential
for functions of the
proteins

Voet D, Voet J, and Pratt CW (2013)

Amino acids

(Predominate at neutral pH)

• Amino group protonated
• Carboxyl group deprotonated
Ionization state of an amino acid depends on pH

• pKa1: COOH ⇆ COO– + H+

• pKa2: NH3+ ⇆ NH2 + H+
• pKa3: side chain group
• When pH > pKa, the deprotonated forms (COO– and NH2) dominate
• When pH < pKa, the protonated forms (COOH and NH3+) dominate

pKa1 = 2.34 pKa2 = 9.6

High pH
Low pH • amino group protonated
amino group and
amino group and • carboxyl group
carboxyl group carboxyl group
deprotonated
protonated deprotonated
Zwitterionic form
 pKa1 = 2.18 pKa2 = 8.95 pKa3 = 10.53

Physiological pH (7.4)

Lysine carries a positive charge on

its side chain at physiological pH
pKa1 = 2.19 pKa3 = 4.25 pKa2 = 9.67

Physiological pH (7.4)

Glutamate carries a negative charge

on its side chain at physiological pH
Biological roles of amino acids
• Building blocks for synthesis of peptides and proteins
• Regulators of metabolic pathways
• For synthesis of other small molecules (e.g. aspartate
for the biosynthesis of pyrimidine, purine nucleotides)
• As intermediates in metabolisms (e.g. arginine in
disposal of nitrogen)
• As energy source
• As neurotransmitters or as precursors of
neurotransmitters and hormones
 Amino acids as intermediate Link between amino acids and to
in metabolism (e.g. urea glucose metabolism.
cycle)
Aspartate involved in
biosynthesis of
pyrimidine

Berg JM (2015) Biochemistry 8th ed

Glutamate as a neurotransmitter

Histidine as precursor of histamine Tryptophan as precursor of serotonin

General structural formula for
α-amino acid
COO- carboxyl group
amino H N+ C H
group 3
R
Side-chain group
 General structural formula for
α-amino acid

• α-carbon is tetrahedral
• In α-amino acids, 4 different substituents attached to the α-
carbon (except glycine)
• 2 different ways to connect 4 different substituents to a
tetrahedral carbon atom → 2 molecules with different spatial
orientations of atoms (stereoisomers)
Amino acids are chiral molecules
• Chiral: non-superimposable on its mirror image
• Enantiomers: One of a pair of molecular entities which
are mirror images of each other and non-superimposable

L-enantiomer D-enantiomer
Non-superimposable mirror images of each other (enantiomers)
Enantiomers are also known as optical isomers:
A pair of enantiomers rotate plane-polarized light by equal amounts but in
opposite directions.

Dextrorotatory – rotate plane of polarised light to right

Levorotatory – rotate plane of polarised light to left
https://www.khanacademy.org/
Enantiomers
• Non-superimposable mirror images of each other
• L- or D-enantiomers

Fischer projections
Vertical lines = bonds below the plane of the
paper; pointing away from you
Horizontal lines = bonds above the plane of the
paper; pointing towards you

The carbon chain is oriented vertically with the

carbonyl carbon at the top.
D: nonhydrogen substituent is drawn to the
right
Enantiomers
• Non-superimposable mirror images of each other
• L- or D-enantiomers

* *
* * *
* * * *
* *
* *
*: chiral carbon
For carbohydrates, the enantiomer is defined by
the bottom chiral carbon when the carbon chain
is oriented vertically with the carbonyl carbon at
the top.
D: nonhydrogen substituent is drawn to the right

Fischer projection
D/L-nomenclature for amino acids are based on similarity to glyceraldehyde
Only L-amino acids are used for protein biosynthesis.
Note that not all L-amino acids are levorotatory.
 • L form: Looking down the H-Cα bond (with
hydrogen nearer to you), groups attached
to Cα spell CORN (R is the sidechain) in a
clockwise direction.
• L form: wrapping your left hand fingers
around the direction of CORN (−CO, −R,
and −N groups in order) your thumb points
toward the direction of the hydrogen
atom.
https://www.cryst.bbk.ac.uk/education/AminoAcid/stereochem.html
• D form: Looking down the H-Cα bond
(with hydrogen nearer to you), groups
attached to Cα spell CORN (R is the
sidechain) in a anti-clockwise direction.
• D form: wrapping your right hand fingers
around the direction of CORN (−CO, −R,
and −N groups in order) your thumb points
toward the direction of the hydrogen
atom.
Note that:
• L-glyceraldehyde rotates plane-polarized light to the left (levorotatory)
• D-glyceraldehyde rotates plane-polarized light to the right
(dextrorotatory)

• D/L-nomenclature in other carbohydrates or amino acids are based on

similarity to the glyceraldehyde.
• However, it does not necessary indicate rotating plane-polarized light
to the left or right. E.g. D-glucose is dextrorotatory but D-fructose is
levorotatory; L-serine is levorotatory but L-alanine is dextrorotatory
The importance of chirality
Shape of a molecule is
important for its function:
Interactions between
biomolecules are stereospecific

Enantiomers behave differently

in biological systems:
enzymes/proteins are chiral
molecules and can discriminate
between enantiomers, e.g.
ribosome can discriminate
between L- and D-amino acid for
protein synthesis.

Interaction between two enantiomers of a

chiral compound and its binding site Chemistry for the Biosciences, OUP
Chiral drugs

D-Dopa L-Dopa
Biologically inactive Effective against
Parkinson’s disease

(S)-thalidomide (R)-thalidomide
Bind to and inactivates the protein Sedative
cereblon, cause birth defects
 The importance of chirality – the Thalidomide story

https://www.youtube.com/watch?v=mrTHfBCduRA
Importance of D-amino acids
• D-amino acids in protein can produced by
• incorporation of D-amino acids produced by amino acid
racemase (e.g. serine racemase)
• non-enzymatic racemization associated with aging
• post-translational modification (e.g. peptidyl aminoacyl
L/D isomerase)

serine
racemase

Racemase reaction
 Importance of D-amino acids
• D-amino acids are abundant in
bacteria e.g. D-Glu and D-Ala
are found in peptidoglycan cell
wall of bacteria.

Peptidoglycan in bacterial cell wall

https://microbeonline.com/peptidoglycan-mureinmucopeptide- G: N-acetylglucosamine
structure-and-medical-significance/ M: N-acetylmuramic acid
 Importance of D-amino acids
• D-serine and serine racemase are present in human brain
• D-serine as modulator of N-methyl-D-aspartate (NMDA)
receptors

https://www.mdpi.com/1422-0067/22/10/5343/htm DAO = D-amino-acid oxidase

Accumulation of D-aspartate with
ageing
L-aspartic acid D-aspartic acid

Aspartic acid racemisation in dentine

as a measure of ageing
Nature (1976)
Quick summary
• Structure of alpha amino acids
• D,L-enantiomer
• L-amino acids for protein synthesis
• Properties of amino acids determined by side chain groups;
ionization states depend on pH
• 20 standard amino acids and 2 rare amino acids
(selenocysteine, pyrrolysine) for protein synthesis
• UGA codon for selenocysteine; UAG codon for pyrrolysine
• Amino acids are involved in many metabolic processes
END