AMINO ACIDS

O
IN
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A
E
TH

IC
S
A

S
D
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TS
I
UN

D
N
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G
IN
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BU

S
K
C
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B

F
O

NS
I
TE
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BASIC STRUCTURES

An amino acid contains:

a central carbon bonded to a carboxyl group (-COOH),
an amino group (NH2), an
R-group, and
a hydrogen.
The R-group is what varies between the 20 amino acids and gives
them unique characteristics.
The covalent bonds between amino acids are called peptide bonds.
It is a bond between the carboxyl group of one amino acid and
the amino group of another amino acid.

Abbr
ev.

Full
Name

Side chain type

A Ala Alanine

hydrophobic

C Cys Cysteine

hydrophobic
(Nagano, 1999)

D Asp Aspartic a acidic

cid

Remarks
Very abundant and versatile. It behaves fairly
neutrally and can be located in both
hydrophilic regions on the outside of the
protein and hydrophobic interior areas.
The sulfur atom binds readily to heavy metal
ions. Under oxidizing conditions, two cysteines
can be joined together by a disulfide bond to
form the amino acid cystine. When cystines
are components of a protein, they enforce
tertiary structure and makes the protein more
resistant to unfolding and denaturation;
disulfide bridges are therefore common in
proteins that have to function in harsh
environments, digestive enzymes (e.g., pepsin
and chymotrypsin), structural proteins (e.g.,
keratin), and proteins too small to hold their
shape on their own (eg. insulin).
Behaves similarly to glutamic acid. Carries a
hydrophilic acidic group with strong negative
charge. Usually is located on the outer surface
of the protein, making it water-soluble. Binds
to positively-charged molecules and ions,

Abbrev Full
.
Name

Side
chain
type

Remarks

Phenylalanine, tyrosine, and tryptophan contain large

rigid aromatic group on the side chain. These are the
hydrophob
*F Phe Phenylal
biggest amino acids. Like isoleucine, leucine and
ic
anine
valine, they are hydrophobic and tend to orient
towards the interior of the folded protein molecule.
Because of the two hydrogen atoms at the carbon,
glycine is not optically active. It is the smallest amino
hydrophob
G Gly Glycine
acid, rotates easily, and adds flexibility to the protein
ic
chain. It is able to fit into the tightest spaces (e.g., the
triple helix of collagen).
In even slightly acidic conditions, protonation of the
nitrogen occurs, changing the properties of histidine
and the polypeptide as a whole. It is used by many
*H His Histidine basic
proteins as a regulatory mechanism, changing the
conformation and behavior of the polypeptide in acidic
regions such as the late endosome or lysosome,
enforcing conformation change in enzymes.
Isoleucine, leucine and valine have large aliphatic
hydrophobic side chains. Their molecules are rigid, and
hydrophob their mutual hydrophobic interactions are important
*I Ile Isoleucin
ic
for the correct folding of proteins, as these chains tend
e

Abbre
v.

*K Lys

*L Leu

*
Met
M

N Asn

Full
Name

Side chain
type

Remarks

Behaves similarly to arginine. Contains a long flexible

side-chain with a positively-charged end. The
flexibility of the chain makes lysine and arginine
suitable for binding to molecules with many negative
Lysine
basic
charges on their surfaces. (e.g., DNA-binding proteins
have their active regions rich with arginine and
lysine.) The strong charge makes these two amino
acids prone to be located on the outer hydrophilic
surfaces of the proteins.
Leucine hydrophobic Behaves similar to isoleucine and valine.
Always the first amino acid to be incorporated into a
protein; sometimes removed after translation. Like
cysteine, it contains sulfur, but with a methyl group
Methionin hydrophobic
instead of hydrogen. This methyl group can be
e
activated, and is used in many reactions where a new
carbon atom is being added to another molecule.
Asparagin
hydrophilic Neutralized version of aspartic acid.
e

Abbre
v.

Full
Name

P Pro Proline

Q Gln

Side chain
type

Remarks

Contains an unusual ring to the N-end amine group,

which forces the CO-NH amide sequence into a fixed
conformation. Can disrupt protein folding structures
hydrophobi
like helix or sheet, forcing the desired kink in the
c
protein chain. Common in collagen, where it
undergoes a posttranslational modification to
hydroxyproline. Uncommon elsewhere.

Glutamin
Neutralized version of glutamic acid. Used in proteins
hydrophilic
e
and as a storage for ammonia.

*R Arg Arginine

Basic

Functionally similar to lysine.

S Ser Serine

Serine and threonine have a short group ended with a

hydroxyl group. Its hydrogen is easy to remove, so
serine and threonine often act as hydrogen donors in
Hydrophilic
enzymes. Both are very hydrophilic, therefore the
outer regions of soluble proteins tend to be rich with
them.

Abbrev.

Full
Name

Side chain
type

Remarks

*T Thr

Threonine hydrophilic

Behaves similarly to serine.

*V Val

Valine

Behaves similarly to
leucine. See isoleucine.

*W Trp

Behaves similarly to phenylalanine and

Tryptopha
hydrophobic tyrosine (see phenylalanine). Precursor of
n
serotonin.

Tyr

Tyrosine

hydrophobic

isoleucine

and

Behaves similarly to phenylalanine and

tryptophan
(see
phenylalanine).
hydrophobic
Precursor of melanin, epinephrine, and
thyroid hormones.

GENERALITIES
Classification
Neutral
Acidic
Basic

Neutral
Aliphatic
Aromatic
Heterocyclic
S-containing AA

Generalities - neUTRAL

A.

Aliphatic

1.

Glycine (Gly) (G) alpha

amino acetic acid
Alanine (Ala) (A) alpha
amino propionic acid
Valine (Val) (V) alpha
amino iso valeric acid
Leucine (Leu) (L) alpha
amino iso caproic acid
Isoleucine (Ile) (l) alpha
amino B methyl valeric
acid

2.
3.
4.
5.

Above = Simple monoamino

monocarboxylic acids

Hydroxy Amino Acids they

contain OH group in the side
chains

6. Serine (Ser) (S) or alpha

amino hydroxy propionic
acid
7. Threonine (Thr) (T) or alpha
amino hydroxybutyric
acid

generalities

B. Aromatic
8. Phenylalanine
(Phe) (F) or alpha
amino phenyl
propionic acid

9. Tyrosine (Tyr) (y)

or parahydroxy
phenylalanine or
alpha amino
parahydroxy
phenylpropionic acid

C. Heterocyclic AA
10. Tryptophan (Trp) (W)
alpha amino 3
indole propionic

- often considered as
aromatic AA since it has
aromatic ring in its
structure.
11. Histidine (His) (H)
alpha amino imidazole propionic acid
Histidine is basic in
solution on account of the
imidazole ring and often
considered as Basic AA

generalities

D. Imino Acids
12. Proline (Pro) (P) or
Pyrrolidone 2 carboxylic
Acid
13. Hydroxyproline (Hyp) or
4 Hydroxy pyrrolidone 2
carboxylic acid
Proline & Hydroxyproline
do not have a free _NH2
group but only a basic
pyrrolidone ring in which the
Nitrogen of the Imino group
is in ring but can still
function in the formation of
peptides.
Are called Imino Acids.

E. S containing Amino Acids

- contains 2 sulfur
containing AA
14. Cysteine (Cys) (C) or
alpha amino
mercaptopropionic acid

S S linkage is called a
Disulfide bridge
15. Methionine (Met) (M) or
alpha amino y methylthio - butyric acid

GENERALITIES - ACIDIC

II. Acidic AA

- AA with 2 _COOH groups and 1 _NH2 group

- monoaminodicarboxylic Acids

16. Aspartic Acid (Asp) (P) or alpha amino succinic

acid

Asparagine (Asn) (N) or delta amide of alpha

amino succinic acid

17. Glutamic Acid (Glu) (E) or alpha aminoglutaric acid

Glutamine (Gln) (Q) amide of glutamic acid or 8

amide of alpha amino glutaric acid

GENERALITIES - BASIC

III. Basic AA

- AA with 1 COOH group and 2 NH2

groups

- Diamino monocarboxylic acids

18. Arginine (Arg) (R) or alpha amino 8
guanidino - valeric acid
19. Lysine (Lys) (K) or alpha E diamino

8 hydroxy - - valeric acid

As already mentioned Histidine is also
classified as Basic AA

GENERALITIES
Classification of Amino Acids
based on polarity
of the R group:
4 groups
Polarity reflects the functional
role
of AA in protein
structure

GENERALITIES

1. Non-polar AA
hydrophobic (water hating)
No charge on the R group
Examples are:

Alanine Methionine
Leucine Phenylalanine
Isoleucine
Tryptophan
Valine
Proline

GENERALITIES

2. Polar AA with (+) R group

carries (+) charge
Examples:

Histidine

Arginine

Lysine

3. Polar AA with (-) R group

carries (-) charge
Examples:

Glutamic Acid

Aspartic Acid

GENERALITIES

4. Polar AA with no charge

on R group
no charge on the R group
possess groups

hydroxyl
sulfhydryl
amide
participate in hydrogen bonding of
protein structure
Examples:
Asparagine Glycine
Cysteine
Tyrosine Serine
Threonine
Glutamine

GENERALITIES

Zwitterion or dipolar ion:

Zwitter
from German word means
hybrid

Zwitter ion (or dipolar ion)

a hybrid molecule containing (+)
and (-) ionic groups

GENERALITIES

AA rarely exist in a neutral form with free

carboxylic (-COOH) and free Amino (-NH2)
groups
Strongly acidic pH (low pH) AA (+)
charged (cation)
Strongly alkaline pH (high pH) AA (-)
charged (anion)
Each AA has a characteristic pH (e.g.
Leucine, pH 6.0), at which it carries both
(+) and (-) charges and exist as zwitterion

GENERALITIES

Isoelectric pH (symbol pI)

the pH at which a molecule exists as a
Zwitterion or dipolar ion and carries
no net charge
Molecule is electrically neutral

GENERALITIES
Tryptopha
n

Histidine Arginin
e

Valine

Phenylalanin
e

PV
T
Threonine

TI
M

HAL
L

Leucine

Lysine

Methionin
e
Isoleucine

Essential Amino
Acids

Essential Amino Acids (Bodycannotmaketheseaminoacids,theymustcome

fromfoodoraminoacidsupplements.)
Min
.
Dail Acid
Work
Amino
Sy Abb y
Base # of pathways - Generat s
Acid
m
r
mg Neu. One Pathway
es
With Augments
Isoleucine
1 - threonine -->
1
I
Ile 10 n
muscles
*
isoleucine
blood,
1 - keto-isovalerate
2 Leucine*
L
Leu 14 n
muscle,
--> leucine
hormone
herpes,
2 - asparate -->
calciu
3 Lysine
K
Lys 12 B
triglyceride
lysine
m
s
seleni
Methionin
7 - homoserine -->
hair, skin,
4
M
Met 13 n
cysteine um,
e
methionine
chelator
zinc
Phenylala
3 - chorismate -->
5
F
Phe 14 n
tyrosine B6
depression
nine
phenylalanine
collagen,
3 - aspartate -->
glycine,
6 Threonine T
Thr 7
N
tooth
threonine
serine
enamel
niacin,
Tryptopha
1 - chorismate -->
7
W
Trp 3.5 n
seratoni depression
n
tryptophan
n

Non-Essential Amino Acids (Thebodycanmaketheseaminoacidsfromtheaboveessentialamino

acids.)
Min. Acid
Daily Base # of pathways - One
Amino
Works
Acid
Sym. Abbr mg. Neu. Pathway
Generates With
Augments
4 - valine pyruvate -->
1 Alanine
A
Ala
n
alanine
immune,
polyamines, zinc
2 Arginine* R
Arg
B
4 - citrulline --> arginine
healing,
creatine
(lysine)
muscles
3 - asparate and
3 Asparagine N
Asn
N
CNS
ammonia
Aspartic
3 - glutamate -->
4
D
Asp
A
CNS, brain
Acid
aspartate
homocystein
5 Cysteine
C
Cys
N
4 - serine --> cysteine
B6, Vit.E
skin, hair
e, taurine
Glutamic
3 - ketoglutarate -->
glutamine,
6
E
Glu
A
B6
brain
Acid
glutamate
GABA
2 - glutamate -->
7 Glutamine Q
Gln
N
brain
glutamine
GABA,
8 Glycine
G
Gly
N
2 - serine --> glycine
glutathione
body protein
taurine
blood,
9 Histidine* H
His
B
1 - histidinol --> histidine histamine
allergy, sex
4 - l-glutamine -->
hydroxyproli
collagen,
10 Proline
P
Pro
n
Vitamin C
proline
ne
elastin
1 - phosphoglycerate --> cysteine,
11 Serine
S
Ser
N
choline
blood sugar
serine
glycine
2 - phenylalanine -->
thyroxin,
12 Tyrosine
Y
Tyr
N
B6
thyroid
tyrosine
melanin
* = These are Essential for infants, since their bodies cannot produce them yet.

Other Amino Acid Factors

Carnitin
e

Ca
r

carnitine -->
butyrobetaine -->

Lysine,
Vitamin
methioni
C
ne

fat
metabolism

Ornithin
zinc
e

urea cycle

Citrullin
e

Cit -

argenine -->
citrulline -->
ornithine

Hydroxy
proline

Hy
p

proline -->
hydroxyproline

Vitamin
C

collagen

Ornithin
e

Or
n

argenine -->
citrulline -->
ornithine

urea cycle

- Taurine -

Ta
u

methionine -->
GABA,
cysteine --> taurine glycine

B6

heart, bile

The above are precursors for, or important products of, the 20 "true"
amino acids listed above.

AMINO ACID SYNTHESIS

ALL ARE SYNTHESIZED FROM COMMON

METABOLIC INTERMEDIATES

NON-ESSENTIAL
Transamination of -KETOACIDS that are
available as common intermediates

All except tyrosine are derived from one of the

following common intermediates: pyruvate,
oxalacetate, -KG, 3-phosphoglycerate

ESSENTIAL
Their -KETOACIDS are not common
intermediates (Enzymes needed to form
them are lacking)

Amino Acids
A
m
i
n
o
A
c
i
d
M
e
t
a
b
o
l
i
s
m

Glucogenic

Glucogenic
and Ketogenic

Ketogenic

Non-Essential
AA

Alanine
Asparagine
Aspartate
Cysteine
Glutamate
Glutamine
Glycine
Proline
Serine

Tyroxine

Essential AA

Arginine
Histidine
Methionine
Threonine
Valine

Isoleucine
Phenylalanine
Tryptophan

Leucine
Lysine

Glucogenic amino acids that give rise to pyruvate

and citric acid cycle intermediates that can be
turned into glucose
Ketogenic amino acids that give rise to
acetoacetate and acetyl-co-A, which do not yield

O
IN
AM

ID
C
A

Y
C
EN ISM
I
F
IC O L
F
O
E
S
D TAB
R
E
E M
E
D
M
M
S
R LI ZY D
O
I
IS BO EN AC
D TA C
D
E IFI INO
E
M C M
IT
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PE A
E
S
F
H
:
O
Y
N
IT RS
,I
L
E
A
O
R
R
A
M
R
R ER
O

N
N
B
R
A
O
B

IN

aminoacidopathies

TYROSINEMIA

DEFECTIVE PROCESS: AMINO ACID TRANSPORT

EXCRETION OF TYROSINE AND TRYPTOPHAN CATABOLITES
IN URINE
DEFECTIVE ENZYME:
TYROSINE AMINOTRANSFERASE (II);
4-HYDROXY-PHENYLPYRUVATE OXIDASE (III);
FUMARYLACETOACETATE HYDROLASE (I)

ALKAPTONURIA

DEFECTIVE PROCESS: TYROSINE

DEGRADATION
DEFECTIVE ENZYME: HOMOGENTISATE1,2-DIOXYGENASE
Original inborn error of metabolism
Darkening of urine at long standing
OCHRONOSIS generalized
pigmentation of tissues and arthritislike
degeneration

PHENYLKETONURIA
DEFECTIVE PROCESS: CONVERSION OF
PHENYLALANINE TO TYROSINE
DEFECTIVE ENZYME: PHENYLALANINE
HYDROXYLASE (Phenylalanine-4-mono-oxygenase)
An autosomal recessive trait urine has a musty
odor
Compounds seen in both urine and blood:
Phenylpyruvic acid primary catabolite
Phenyllactic acid product of deaminzation
Phenylacetylglutamine produced from oxidation
of phenylpyruvic acid

PHENYLKETONURIA

NOT RESPONSIVE TO DIET: DEFICIENCY OF ENZYME S NEEDED

FOR THE REGENERATION AND SYNTHESIS OF
TETRAHYDROBIOPTERIN (BH4)
High phenylalanine and deficiency of production of
neurotransmitters from tyrosine and tryptophan
Administration of L-dopa and 5-OH tryptophan
SCREENING: GUTHRIE BACTERIAL INHIBITION ASSAY B. subtilis +
2-thienylalanine
Semi-qualitative method: phenylalanine >2-4 mg/dL will
result to bacterial growth indicative of a POS (+) result
Microfluorometric assay based on the fluorescence complex
formed of phenylalanine-ninhydrin copper in the presence of
dipeptides (L-leucyl-L-alanine)
Quantitative method: filter paper is pretreated with
trichloroacetic acid added with ninhydrin, succinate and
leucylalanine in the presence of copper tartrate and read at
excitation and emission wavelengths of 360nm and 530nm
HPLC reference method (1.2 -3.4 mg/dL)

MAPLE SYRUp DISEASE

DEFECTIVE PROCESS: METABOLISM OF THREE ESSENTIAL BRANCHEDCHAINAMINO ACIDS (LEUCINE, ISOLEUCINE AND VALINE)
DEFECTIVE ENZYME: BRANCHED CHAIN -KETO ACID DECARBOXYLASE
COMPLEX
Burnt sugar odor of urine, breath and skin
Screening: Modified Guthrie test metabolic inhibitor of B. subtilis
which is 4-azaleucine is impregnated in the medium
POS (+) for MSUD = bacterial growth
Microfluorometric assay using leucine dehydrogenase
Filter paper specimen is treated with methanol and acetone to
denature hemoglobin
The NADH fluorescence produced is measured at 450nm; excitation
wavelength at 360nm
Confirmed diagnosis is based on finding increased plasma and urinary
levels of the three branched-chain amino acids and their ketoacids with
LEUCINE (highest: above 4mg/dL)
Prenatal diagnosis: measuring decarboxylase enzyme concentration in
cells cultured from amniotic fluid

CYSTINURIA

DEFECTIVE PROCESS: AMINO ACID TRANSPORT

SYSTEM RATHER THAN A METABOLIC ENZYME
DEFICIENCY
20 30 fold increase in the urinary excretion of
cystine as a result of genetic defect in the renal
resorptive mechanism
Other amino acids excreted: ornithine, lysine and
arginine
Cystine being relatively insoluble and once
accumulated will tend to precipitate in the
kidney tubules forming calculi
Remedy: high fluid intake and alkalinizing the
urine: penicillin
Diagnosis: Cyanide-nitroprusside (red-purple color)

ARGININOSUCCINIC ACIDURIA
AND PROCESS:
CITRULLINEMIA
DEFECTIVE
UREA CYCLE
DEFECTIVE ENZYME: ARGININOSUCCINIC
ACID LYASE
Decrease in activity of ASA synthetase
Citrullinemia
Citrulline is elevated in MS/MS
Argininosuccinic aciduria milder
elevations
Citrullinemia dramatic elevations
* Ornithine and arginine are seen
increased in older infants

Isovaleric acidemia

DEFECTIVE PROCESS: DEGRATIVE

PATHWAY OF LEUCINE
DEFICIENCY ENZYME: ISOVALERYL-CoA
DEHYDROGENASE
Sweaty feet odor urine
Elevations of glycine conjugate:
isovaleric acid and isovalerylglycine