NAME: TAHA UD-DIN

SON OF: MUHAMMD ASHRAF UD-DIN

SEAT # : EH2009071

DEPT: CHEMISTRY

ASSINGMENT: CHEMISTRY OF NON-

PROTEINOGANIC AMINO
ACID
PROFESSOR: DR. SYED MUHAMMAD SAAD

SUBMITTED TO SYED MUHAMMAD SAAD

 INDEX
 INTRODUCTION OF NON PROTEINOGENIC AMINO
ACIDS

 STRUCTURES OF NON PROTEINOGENIC AMINO ACIDS

 ALPHA AMINO ACIDS

 NON-ALPHA AMINO ACIDS

 DETAILS OF ALPHA AMINO ACIDS

 NON PROTENOGANIC AMINO ACID OVERVEIW

 NON AMINO ACIDS

 TYPES OF AMINO ACIDS

 POST-TRANSLATION PROTEIN MODIFICATIONS

 ADDITON OF CHEMICAL GROUP

 CONCLUSION

 REFERENCE

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 NON PROTEINOGENIC AMINO ACID

INTRODUCTION:
The amino acids never found in protein but found in many bells you can important
processes
More than 900 non protein amino acids have been reported from different plants
including leguminosoe, liliaceous, spindaceae cycadaceae ,composite, Rubiaceae And
lecythidaceae
Non – Protein amino acids are most often found in legumes and are
mainly abundant in seeds.
Commonly consumed non protein genic sources are alfalfa and lentils, but others are
inadvertently harvested with crop species for example BMAA the non-protein genic
amino acid has been linked to shellfish usage and proximity to takes with
cyanobacteria alga blooms.
Some non-protein genic amino acids have structure that closely resembles
protein Amino acid, during translation process they can be mistakenly incorporated
into protein. For this to happen, the concentration of non-protein genic amino acids
must be in high enough in the cell to successfully compete with protein Amino acid.
The mis-incorporation of non-protein Amino acid can result in
defective structure and function. The most common effect is aggregation and tangling
of protein. The misincorporated non protein can affect the severity of the damage.
One example of this motor neurons because they can't get rid of terminally
aggregated protein by distributing them to daughter cells motor neurons are
particularly vulnerable are also susceptible because of their length which means
aggregation can fatally damage transport along the axon
Disincorporation of non-protein genic amino acids into proteins can cause
misfolding, losing aqueous solubility and productions of auto florescent material in
risk. There are also some non-protein Amino acid that are not dangerous to humans.
Disease associated with non-protein genic amino acids
These are two non-protein genic amino acids that are commonly misincorporated into
proteins are canaries and L-dopa(3,4 dihydrophenylalanine ), canaries is lethal to rats
when in high concentration as it originates from a species of bean where it uses the
Amino acid to kill the larvae if predators.
The other important non- protein Amino acid is BMAA(B-N methylamine-L-
alanine ) found in microorganism, but there are other evidences too that BMAA can
be misincorporated but L-series can also inhibit BMAA disincorporation.

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 The BMAA disincorporation shown to occur in neuroproteins and results in many
alonomalities,such as buninabodies,lewy body inclusion, senile plaques and
neurofibrillary tangles.BMAA disincorporation has also been shown to cause
apoptosis in neuroblastoma calls when in vitro.the effect of the disincorporation of
BMAA is associated with neurodegenerative disease ALS.
Alpha syncline that's misfiled brain cells protein can cause a neurodegenerative
cascade of MOs folded proteins and it is hypothesized due to misfiled proteins,
similar cascade could occur from non-protein Amino acid disincorporation.
A dangerous non protein Amino acid is homoarginine from legumes while it's effects
have been disputed, evidence suggests this non protein Amino acid also affects the
brain. Homoarginine stopped the uptake of lysine and arginine by the brain in mice
.these effects have not been found in humans, but it is an uncompetitive inhibitor of
human liver and bone alkaline phosphatases
Some less deadly non protein Amino acid also found for example the mushroom
copious atramentarius contain cornpone( N5 1-hydroxy cyclopropyl -L-glutamine)
causes severely unpleasant which inhibit alcohol dehydrogenase ,but not fatal,
effects,hypoglycin more seriously no protein Amino acid have been tentatively linked
with its structural analogy leucine, which is essential for normal development

STRUCTURES

Non-Protein amino acids with no cytotoxicity have been known to be

incorporated into protein

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 For Example
Tyrosine and tryptophan residues in some protein have been substituted with n-
fluorotyrosin and 4- fluorotryptophan, without any effect on the protein function and
the 19F nuclei have been used as a magnetic resonance.
1NPA that received some attention in canavinin L-2- amino 4 (guonielinoxyl butyric
acid), the gunidinoxy structural analogue of arginine.

The NPAA are classified as alpha and non- alpha amino acids.

1) ALPHA AMINO ACIDS

a) Ornithine
b) Citrulline
c) Arginosuccinic acid
d) Thyroxin
e) Triodiothroxine
f) S- Adenosylmethionine
g) Homocysteine
h) 3,4 dihydroxyphenylalanine
i) Creatinine
j) Ovathiol
k) Azaserin

2) NON-ALPHA AMINO ACIDS

a) Beta-alanine
b) Beta -aminoisobutrycacid
c) Gama- aminoisobutrycacid(GABA)
d) Aminolevulinic acid(ALA)
e) Taurine

1) ALPHA –AMINOACIDS

a) Ornithine
It is the precursor of polyamine. Hydrolytic cleavage of guanido group of
arginine, catalysed by liver arginine, releases urea.

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b) Citruline
It is an intermediate in biosynthesis of urea.

c) Arginosuccinic acid
It is an intermediate in biosynthesis of urea .it inter links aspartate with Citruline
via the amino group of aspartate provides the second nitrogen of urea.

d) Tyrosine and Triodiothroxine

Thyroxin forms norepinephrine and epinephrine and following iodination the
thyroid hormone become Triodiothroxine and thyroxin.

e) S- Adenosylmethionine Homocysteine
It is the principal source of methyl groups in metabolism contributes its carbon
skeleton to the biosynthesis of the spermine and spermidine.

f) 3-4 dihydrophenylalanine
Natural cells converts tyrosine to epinephrine and norepinephrine.
While dopa is also an intermediate in the formation of melanin, and different
enzymes hydroxylase, tyrosine in melanocytes.

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g) Creatinine
It is found in muscle from creatine phosphate by irreversible, no enzymatic
dehydration and also loss of phosphate.
Glycine, arginine and methionine all participates in creatinine
biosynthesis.Synthesis of creatine is completed by methylation of
granidoacetate by S Adenosylmethionine.

Normal Values
Creatinine: 200mol/L (44-80mol/L).
Female: 44-80 mol/L (0.5-0.9 mg/mL)
Male: 53-106 mol/L (0.6-1.2mg/mL)

h) Ovathiol
Sulphur containing amino acids found in fertilized egg and acts as oxidant.

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i) Azaserin
Purine deficiency states while rare in humans, generally reflect a deficiency of
fatty acids.

NON PROTENOGANIC AMINO ACID OVERVEIW

3) Non-Amino acids
They are present in a free form including alanine, aminoisobutryiate and
amino butyrate.
Alanine also present in coenzyme A and in alanyldipeptide carinosine, and
homocarnosine.

a) Beta-Alanyl and Aminoisobutryiate

Both are formed during catabolism of pyrimidine’s uracil and thymine.

b) Beta-Analyl dipeptide
The alanyl dipeptide canonise and anserine enhance copper uptake.
Analyl buffers the pH of anaerobically contracting muscles.

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c) Gama- Amino butyrate
It function in brain tissue as inhibitory neurotransmitter by altering
transmembrane potential difference.
GABA is formed by decarboxylation of glutamate by L decarboxylation of
glutamate. Transmission of aminobutrate forms succinate semialdehylde
which can be reduced to hydroxybutrate L acetate or can be oxidized to and
then via the citric acid cycle to CO2 and H2O.

d) Taurine
Also 2 aminoethylsulphuric acid is a non-protein. In humans it is considered as semi
essential amino acid since to can be formed from other suphoninc amino acid such
that methionine and cysteine.

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 TYPES OF AMINOACIDS

They can be divided into three types

 Rare amino acids
 Post-translation protein modification
 Biogenic amines

1) RARE AMINOACIDS
Those amino acids that arise during metabolism reaction.
Four important rare amino acids

 ORNITHINE
 CITRULINE
 DOPA
 SELENOCYSTEINE

SELENOCYSTEINE
Cysteine analogue for example, glutathione peroxidase enzyme which is also
seleno enzyme also known as Seleno-Glutathione peroxoidase.its main role is
to protect the organism from oxidative cleavage.

2) POST-TRANSLATION PROTEIN MODIFICATIONS

The chemical changes that occur after a protein has been produced.
It can impact the structure, electrophilicity and interaction of protein.
The modification based on 5 types
a) Based on addition of chemical groups
b) Based on addition of complex groups
c) Based on addition of polypeptide
d) Based on the cleavage of protein
e) Based on the amino acids modification

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  Addition of chemical group
These are of 4 type

a) Phosphorylation
b) Acetylation
c) Hydroxylation
d) Methylation

1) PHOSPHORYLATION
Perform by enzyme called kinases. Addition of phosphate group or serine, threonine,
or tyrosine residues which makes phosphoserine, phosphotyrosine and
phosphothreonine this is called Phosphorylation of protein.

2) ACETYLATION
Addition of acetyl group in a protein.
For example: acetylation of lysine in to acetyl lysine by an enzyme LAT
(Lysine Acetyl Transferees).

3) HYDROXYLATION
The addition of hydroxyl group to protein by enzyme .hydroxylase and acid into
converting compound into hydrophilic compounds

4) METHYLATION
Addition of methyl group to lysine or arginine residues of protein.
There are three types of complex group
 Glycosylation
 Ampylation
 Lipidation

A) GLYCOLYSATION
Addition of an oligosaccharides termed to either a nitrogen atom or oxygen
atom which respectively called N-linked glycosylation or O linked
glycosylation

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B) AMYLATION
Addition of AMP (adenosine monophosphate) to a protein. It involves
formation of a phosphodiester between the phosphate group of AMP and
hydroxyl group of protein.

C) LIPIDATION
It is basically covalent binding of a lipid to a protein.

D) ADDITION OF POLYPEPTIDES
Ubiquitination is the addition of a protein found ubiquitously to the lysine
residue of a substrate. It can be single chain mono ubiquitination or several
molecules called polyubiquitination.

E) CLEAVAGE PROTEIN
It is a proteolysis. Proteolysis is breakdown of protein into smaller
polypeptides or amino acids.

F) AMINOACIDS MODIFICATIONS

It is a deamination. Deamination is a removal or conversion of arginine or

glutamine residues to another functional group such as asp arginine to aspartic
acid .This can change the stability, structure and function of protein.

G) BIOGENIC AMINES

Amino acids can be broken down by decarboxylation.

Biogenic amines amino propanol is derived from threonine which function as
vitamin B12
Gamma amino butyrate is derived from glutamate and is neuron transmitter.
Dopamine is derived from DOPA which also function as neurotransmitter

CONCLUSION
With the development of modern chemistry and biology non photogenic amino acid
will be a powerful tool for drugs based on like properties’ of peptide medicines due to
smaller size and structure compared to large protein are simpler it can be changed by
introducing NPAAs in its sequence .peptides composed of natural amino acids can be

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used as drug candidates in biological conditions this incorporation of NPAA can be
extremely beneficial in improving the stability , permeability and availability of
peptide based therapies.un desired effects such as toxicity and immunogenicity should
also be considered.

REFERENCE:

 PUB MEDICAL CENTRE

 SCIENCE DIRECT
 SLIDE SHARE .NET
 SCIENCE DIRECT

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