1

AMINO ACIDS
GOALS/OBJECTIVES

These 2 lectures will provide knowledge of the
structural definition of amino acids; their
classification; the essential and non-essential
amino acids; protein and non-protein amino
acids; amino acid metabolism; transamination;
urea cycle; amino acid derivatives; and amino
acid-related diseases.
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AMINO ACIDS 1
At the end of this lecture students will be
able to:

Define amino acids;
Classify amino acids;
Describe the functions of and differentiate
between the essential and non-essential amino
acids.
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Its easy to think that amino acids are only
important as the building blocks for proteins,
however, this is totally untrue.
There are about 300 different amino acids
known, but only 20 of these occur in protein
structure, and even those dont only occur in
proteins.
Amino acids have functions as themselves, as
well as having a wide range of non-protein
derivatives.
Even the amino acids included in a protein
structure may be modified post protein
synthesis and so be different to the original.

4
To be an amino acid requires a central carbon,
-carbon, to which 4 different groups are
attached. Specifically an amino group (-NH
2
,
-NH
3
+
), a carboxylic group (-COOH, -COO
-
),
a hydrogen (-H) and some other group (-X).


H
l
NH
2
C COOH
l
X

5
Apart from glycine, in which the X group is
another hydrogen, all the amino acids occur in
2 different mirror-image (enantiomer) forms.
Depending on the orientation, they are called
D- (dextro) or L- (levo). All amino acids in
proteins are in the L- configuration, because
protein synthesis enzymes only recognize and
insert L- amino acids into the protein chain.
Since all the other groups are the same, it is
the side chain (X group) that determines the
properties of the amino acid.
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ENANTIOMERS
D-SERINE L-SERINE


H H



COOH C NH
2
H
2
N C COOH


CH
2
OH CH
2
OH
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When an amino acid is part of a protein, the
amino and carboxy groups are linked in peptide
bonds, so it is the side chains that are the
prime determinants of the conformation,
charge and, ultimately, the properties of the
protein.
Amino acids with charged, polar or hydrophilic
side chains are mostly on the protein exterior
surface, while non-polar, neutral amino acids
are mainly in the hydrophobic interior of the
structure.
The 20 amino acids found in proteins are
classified according to their side chain
structure.
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Aliphatic amino acids are those with saturated
side chains. Glycine, alanine, valine, leucine
and isoleucine make up this group.
Alanine, the commonest amino acid in most
proteins, has a CH
3
as the side group. All the
aliphatic amino acids are hydrophobic and
usually occur with other aliphatic amino acids
in the interior of a protein or a membrane-
straddling region.

9
Aromatic amino acids have some form of ring
structure as the side group. There are 3
found in proteins: phenylalanine, tyrosine and
tryptophan.
Phenylalanine is non-polar and usually occurs in
hydrophobic regions with the aliphatics.
Tyrosine has a weakly acid hydroxyl group,
while tryptophan has an extra NH group in 1
of its rings, so both are partially polar, and
may be in either the hydrophobic or
hydrophilic regions.
Proteins are often measured by absorption of
light in the 275-285nm region. Most of this
absorption is from the aromatic amino acids.
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Neutral polar amino acids contain hydroxyl or
amide side chains.
Serine and threonine have hydroxyls, and
commonly occur at the active site of hydrolase
enzymes. They are important in linking
saccharides as part of glycoproteins and
sphingolipids, and also work via their
phosphokinases in many regulatory processes,
especially in energy metabolism and fuel
storage.
Glutamine and asparagine have amides, usually
polar but non-charged under physiological
conditions.
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Acidic amino acids include aspartic acid and
glutamic acid and they possess an extra
carboxyl group in the side chain. Being highly
charged they form part of the hydrophilic
regions of proteins, and are only rarely found
in the hydrophobic regions. Most of the time
they are ionised, and referred to as
aspartate and glutamate.
Basic amino acids include lysine, arginine and
histidine. Lysine contains an extra amine group
in its side chain. Arginine has a guanidine
group as part of its side chain, and the 3
nitrogen groups make arginine the most basic
of all the protein amino acids. Histidine has 2
nitrogen groups as part of a ring in its side
chain.
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Sulphamino acids include cysteine, cystine and
methionine.
Cysteine is converted to cystine by oxidation
and they are usually considered together. The
primary role of cysteine is to form sulphydryl
bonds with other cysteines in other protein
chains (bonding is oxidation so by joining they
become cystines).
Methionine does not form cross-bridges, but
contains a thio-methyl group as part of its
side chain, and is crucial in protein synthesis
and methyl group transfer.
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There is only 1 imino acid, proline. This has
its -carbon as part of a ring that also
includes its -amino group. Because of this
proline in a protein induces a bend in the
polypeptide chain, allowing for significant
direction change to the chain. The structure
of proline means that it is an imino acid not
really an amino acid, but given its significance
in proteins it is included with the others.
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Non-protein amino acids are all the other amino
acids found in metabolism, but that do not take
part in protein structures. They have a variety of
roles, depending on where they are found.

Ornithine and citrulline are important
intermediates in liver urea synthesis. Creatinine is
produced as a breakdown product of creatine in
muscle, and gives a good measure of kidney
function. Citrulline is involved with nitric oxide
metabolism, and hence neurotransmitter function.
Carnitine is critical for the -oxidation of fatty
acids in mitochondria. Taurine is involved in bile
salt formation for fat emulsification. Choline is
involved in phosphoglyceride structure, as is
ethanolamine.
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H


H
2
N C COOH


X
Remember the general structure.
When solid amino acids are not charged, ie.
they have NH
2
and COOH.
16
In solution, amino acids can polarise and
become either acidic or basic, depending on
the pH of the medium.










H


H
3
+
N C COO
-


X
17
If the pH is neutral both groups are ionised,
so are charged, but neutral.


+
H
3
N-C-COO
-
pH neutral

If the pH decreases (acidic) the COO
-

becomes COOH, and the amino acid is
positively charged.

+
H
3
N-C-COOH pH low

If the pH increases the NH
3
+
becomes NH
2
,
and it is negatively charged.
H
2
N-C-COO
-
pH high
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Amino acids with extra NH
2
side groups are
not neutral at neutral pH.


+
H
3
N
+
H
3
N-C-COO
-
pH NEUTRAL


+
H
3
N
+
H
3
N-C-COOH pH LOW
H
2
N
H
2
N-C-COO
-
pH HIGH
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Amino acids with extra COOH side groups are
not neutral at neutral pH.

COO
-
+
H
3
N-C-COO
-
pH NEUTRAL

COOH
+
H
3
N-C-COOH pH LOW
COO
-
H
2
N-C-COO
-
pH HIGH
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So the net effect is for the amino acid to
resist the change in pH.
If the pH is decreasing (H
+
increasing) the
amino acid takes up some of those extra H
+
.
If the pH is increasing (H
+
decreasing) the
amino acid releases some of its H
+
.
This means the pH change is not so large
this is known as buffering.

21
Peptides are formed by condensation of the
-amino group of one amino acid with the -
carboxy of another, this forms a peptide
bond. This is critical for protein structure,
but doesnt only occur in proteins.



H


H
2
N C CO


X
H


HN C COOH


X
22
Many amino acids are part of the structure of
metabolically important short peptides. For
example, glutathione is a vitally important
tripeptide in both protein structure
stabilisation and in antioxidant pathways. It
consists of glutamate-cysteine-glycine. As
part of its cycle, it forms a dimer with a link
between the cysteines of 2 glutathiones.
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NH
2
H O
HOOC C C C N C C N C COOH
O CH
2
H
SH
REDUCED GLUTATHIONE
| CYSTEINE |
S
O CH
2
H
HOOC C C C N C C N C COOH
NH
2
H O

NH
2
H O
HOOC C C C N C C N C COOH
O CH
2
H
S
OXIDISED GLUTATHIONE
| CYSTINE |
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ESSENTIAL AMINO ACIDS.

Some of the 20 'protein' amino acids cannot be
synthesised by mammals but are still required,
and thus are essential amino acids.

The others can be synthesised and thus are not
essential. However, as long as dietary amino acid
intake is adequate, endogenous synthesis does
not have to occur and usually does not.

Tyrosine can be synthesised from phenylalanine
and thus is only essential if phenylalanine is
limiting. Similarly, cysteine can be synthesised
from methionine and thus is only essential if
methionine is limiting.
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AMINO ACIDS

ESSENTIAL COMMON NON-ESSENTIAL

METHIONINE CYSTEINE
PHENYLALANINE TYROSINE
HISTIDINE ALANINE
ISOLEUCINE ARGININE
LEUCINE ASPARAGINE
LYSINE ASPARTATE
THREONINE GLUTAMATE
TRYPTOPHAN GLUTAMINE
VALINE GLYCINE
PROLINE
SERINE


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ESSENTIAL AMINO ACIDS
METHIONINE

Methionine (met or M).Together with cysteine
(cys or C), methionine is one of two sulphur-
containing proteinogenic amino acids. Its
derivative s-adenosyl methionine (SAM) serves
as a methyl donor. Methionine is an
intermediate in the biosynthesis of cysteine,
carnitine, taurine and phospholipids.

CARNITINE
TAURINE METHIONINE
CYSTEINE
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Methionine is one of only two amino acids
encoded by a single codon (AUG). This codon is
also the "start" message that signals the
initiation of protein translation from mRNA. As
a consequence, methionine is incorporated into
the N-terminal position of all proteins during
translation, although it is usually removed by
post-translational modification. Methionine is
converted to s-adenosyl methionine (SAM) by
methionine adenosyl transferase. SAM serves
as a methyl-donor in many reactions and is
converted to s-adenosyl homocysteine (SAH)
and then to homocysteine, which can be used
to regenerate methionine, or to form cysteine.
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PHENYLALANINE

Phenylalanine (abbreviated as phe or F).
Phenylalanine is structurally closely related to
dopamine, epinepherine (adrenaline) and
tyrosine. It is classified as nonpolar because
of the hydrophobic nature of the benzyl side
chain. L-phenylalanine can be converted into
l-tyrosine.
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L-tyrosine is converted into l-dopa, which is
further converted into dopamine,
norepinephrine (noradrenaline), and epinephrine
(adrenaline). The latter three are known as
the catecholamines. Phenylalanine uses the
same active transport channel as tryptophan
to cross the blood-brain barrier, and, in large
quantities, this interferes with the production
of serotonin. The genetic disorder
phenylketonuria (PKU) reflects an inability to
metabolize phenylalanine, and sufferers must
not consume much phenylalanine. This dietary
restriction also applies to pregnant women.
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HISTIDINE

Histidine (abbreviated as his or H) is an
essential amino acid, but only in children.
After a human is a few years old, they will
start to produce enough of this amino acid,
thus making it a non-essential amino acid in
adults.
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The sidechain of histidine is a common
coordinating ligand in metalloproteins and is a
part of catalytic sites in certain enzymes, eg.
carbonic anhydrases. It is a precursor for the
neurotransmitter and allergenic histamine. The
enzyme histidine ammonia-lyase converts
histidine into ammonia and urocanic acid. A
deficiency in this enzyme is present in the
rare metabolic disorder histidinemia.
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HISTAMINE
UROCANIC ACID
HISTIDINE
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ISOLEUCINE

Isoleucine (abbreviated as ile or I) can exist
as four stereoisomers, however, isoleucine
present in nature exists in only one
enantiomeric form.
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LEUCINE

Leucine (abbreviated as leu or L). Leucine is a
major component of the subunits in ferritin
and other buffer and transport proteins. As a
dietary supplement, leucine has been found to
increase the synthesis of muscle proteins.
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Leucine is utilized in liver, adipose tissue, and
muscle tissue. In adipose and muscle tissue,
leucine is used in the formation of sterols,
and the combined usage of leucine in these
two tissues is seven times greater than its use
in the liver.
Maple syrup urine disease (MSUD) is caused
by impaired leucine (and valine and isoleucine)
metabolism and its build up causes delirium
and neurologic compromise and can be life-
threatening.
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LYSINE

Lysine (abbreviated as lys or K)
lysine is a base, as are arginine
and histidine. The -amino group
often participates in hydrogen
bonding and as a general base in
catalysis. Common post-
translational modifications include
methylation of the -amino group,
giving methyl-, dimethyl-, and
trimethyl-lysine. The latter occurs
in calmodulin. Other post-
translational modifications at lysine
residues include acetylation.
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Collagen contains hydroxylysine which is
derived from lysine by lysyl hydroxylase.
Glycosylation of lysine residues in the
endoplasmic reticulum or golgi apparatus marks
proteins for secretion from the cell.

The bacterial degradation of lysine yields
cadaverine as well as putresine, both of which
give the characteristic smell to decaying
flesh.
CADAVERINE PUTRESINE
LYSINE
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THREONINE

Threonine (abbreviated as thr or T).
Together with serine and tyrosine, threonine is
one of three of the 'protein' amino acids with
a hydroxyl group.
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TRYPTOPHAN

Tryptophan (abbreviated as trp or W). L-
tryptophan is the precursor for serotonin,
melatonin and niacin. Malabsorption of
tryptophan causes reduced levels of
tryptophan in the blood and depression. 5-
HTP readily crosses the blood-brain barrier
and is rapidly decarboxylated to serotonin (5-
hydroxytryptamine or 5-HT) and may be
useful for the treatment of depression.
However serotonin has a
Relatively short half-life
Since it is rapidly metabolized
By monoamine oxidase, and
Therefore is likely to have
Limited long term efficacy.
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VALINE

Valine (abbreviated as val or V). Along with
leucine and isoleucine, valine is a branched-
chain amino acid. In sickle-cell disease, valine
substitutes for the hydrophilic amino acid
glutamic acid in hemoglobin. Because valine is
hydrophobic, the hemoglobin does not fold
correctly.
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NON-ESSENTIAL AMINO ACIDS.

CYSTEINE

Cysteine (abbreviated as cys or C) in proteins is
usually in the form of its oxidized dimer, cystine.
Cysteine can usually be synthesized from
methionine. Cysteine is part of the antioxidant
tripeptide glutathione. Cysteine residues crosslink
protein chains. Cysteine is an important source of
sulfur in metabolism. It also has a
high affinity for heavy metals
(mercury, lead, cadmium). Cysteine
blocks the effects of acetaldehyde,
the major by-product of alcohol
metabolism.
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TYROSINE

Tyrosine (abbreviated as tyr or Y) is unique
because of its phenol group. Mammals synthesize
tyrosine from phenylalanine. It occurs in signal
transduction proteins. Tyrosine phosphorylation is
considered to be one of the key steps in signal
transduction and regulation of
enzymatic activity. In the opium
poppy tyrosine is used to produce
morphine.
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ALANINE

Alanine (abbreviated as ala or A) accounts for
7.8% of the primary structure in most proteins.
Alanine plays a key role in the glucose-alanine
cycle between tissues and liver. In muscle, alanine
and -ketoglutarate are formed during glucose
metabolism. They get recycled to the liver where
they feed into gluconeogenesis to re-form
glucose, which returns to muscle.
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ARGININE

Arginine (abbreviated as arg or R)
is important in cell division, wound
healing, ammonia removal, immune
function and hormone release.
Arginine is the immediate precursor
of nitric oxide, urea and ornithine,
and is necessary for the synthesis
of creatine.
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ASPARTATE

Aspartate (abbreviated as asp or D) is, together
with glutamate, classified as an acidic amino acid.
Aspartate is involved in the urea cycle and
participates in gluconeogenesis. Aspartate
stimulates NMDA receptors, though not as
strongly as glutamate does. It serves as an
excitatory neurotransmitter in the brain.
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ASPARAGINE

Asparagine (abbreviated as asn or n) is one of the
20 most common natural amino acids. A reaction
between asparagine and saccharides produces
acrylamide in food when heated to sufficient
temperature. These products occur in baked goods
such as french fries, potato chips, and roasted
coffee. Acrylamide is extremely toxic and has
been reported to be carcinogenic. Asparagine
was first isolated in 1806
from asparagus juice,
in which it is abundant
and was the first amino
acid to be isolated.
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GLUTAMATE

Glutamate (abbreviated as glu or E) is the most
abundant excitatory neurotransmitter in the
mammalian nervous system. Glutamate
transporters are found in neuronal and glial cells,
and rapidly remove glutamate from the
extracellular space. In brain injury or disease,
they reverse and glutamate accumulates outside
cells. This process is part of the
ischemic cascade and is associated
with stroke, autism, mental retardation
and Alzheimer's disease. Glutamate
also serves as the precursor for
the synthesis of GABA. Glutamate
is present in a wide variety of foods
and is responsible for the taste of umami.
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GLUTAMINE

Glutamine (abbreviated as gln or Q) has a side
chain as an amide. It can be considered the
amide of glutamic acid. Glutamine is the most
abundant naturally occurring, non-essential amino
acid in the human body and one of the only amino
acids which directly crosses the blood-brain
barrier. Glutamine has a variety of functions:
DNA synthesis, protein synthesis,
regulation of acid-base
balance in kidney and carrier of
ammonia in plasma. Glutamine is
the precursor for two brain
neurotransmitters: glutamate
and -aminobutyric acid (GABA).
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GLYCINE

Glycine (abbreviated as gly or G) is not common in
most proteins, but collagen contains about 33%
glycine. Glycine is an inhibitory neurotransmitter
in the CNS, especially in the spinal cord,
brainstem, and retina.
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PROLINE

Proline (abbreviated as pro or P) is unique among
the protein-forming amino acids because the -
amino group is secondary. Multiple prolines and/or
hydroxyprolines in a row can create a polyproline
helix, the prime secondary structure in collagen.
The hydroxylation of proline increases the
stability of collagen. Lack of vitamin C can result
in impaired hydroxylation leading to scurvy.
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SERINE

Serine (abbreviated as ser or S) is important in
the synthesis of purines and pyrimidines. It is
important in many enzymes, egs. chymotrypsin,
trypsin. Nerve gases and many insecticides
combine with serine in the active site of
acetylcholine esterase, inhibiting the enzyme
completely. Acetylcholine cannot
be recycled causing inability to
control muscles, asphyxiation, and
death. As part of proteins, its
side chain can be glycosylated,
which may be functionally related
to diabetes.

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THE END