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Biochemistry: Amino acids & peptides

Presentation · February 2021

DOI: 10.13140/RG.2.2.30784.87045

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Biochemistry
rd
3 stage
Lec 1
Amino acids & peptides
By
Omar D. Salman
 Organic Compounds
• Compounds that contain CARBON
are called organic.

• Macromolecules are large organic

molecules.
 Macromolecules
• Large organic molecules.
• Also called POLYMERS.
• Made up of smaller “building blocks”
called MONOMERS.
• Examples:
1. Carbohydrates
2. Lipids
3. Proteins
4. Nucleic acids (DNA and RNA)
 Amino Acids
 Amino Acids are the building units of proteins.
Proteins are polymers of amino acids linked together
by what is called “ Peptide bond” (see latter).
 There are about 300 amino acids occur in nature.
Only 20 of them occur in proteins.
Structure of amino acids:
Each amino acid has 4 different groups attached to α-
carbon ( which is C-atom next to COOH).
These 4 groups are : amino group,
COOH gp, Hydrogen atom and side
Chain (R) R
The basic structure of amino acids differ only in
the structure of the or the side chain (R-group).

L-isomer

L-isomer is normally found in proteins.

• At physiological PH (7.4), -COOH gp is dissociated forming a
negatively charged carboxylate ion (COO-) and amino gp is
protonated forming positively charged ion (NH3+) forming
Zwitter ion
• N.B. Proline is an imino acid not amino acid (see latter)

Classification of amino acids

I- Chemical classification: According to number of COOH and NH2
groups i.e. according to net charge on amino acid.
A- Monobasic, monocarboxylic amino acids i.e. neutral or
uncharged:

R
Subclassification of neutral amino acids:
All structures are required
1- Glycine R= H
2- Alanine R= CH3
3- Branched chain amino acids: R is branched such as in:
a - Valine R= isopropyl gp
b- Leucine R= isobutyl gp
c- Isoleucine R = is isobutyl
R is isobutyl in both leucine and isoleucine but branching is
different: in leucine → branching occurs on γ carbon
in isoleucine→ branching occurs on β- carbon

4- Neutral Sulfur containing amino acids:

e.g. Cysteine and Methionine. What is cystin?

5- Neutral, hydroxy amino acids:

e.g. Serine and Threonine
 Nonpolar (Hydrophobic) R Groups
Glycine (Gly) Methionine (Met)

Alanine (Ala)

Phenylalanine (Phe)

Valine (Val)

Proline (Pro)

Leucine (Leu)

Tryptophan (Trp)

Isoleucine (Ile)
6- Neutral aromatic amino acids:
a- Phenyl alanine : It’s alanine in which one hydrogen of CH3 is
substituted with phenyl group. So it’s called
phenyl alanine
b- Tyrosine: - it is P- hydroxy phenyl alanine
- it is classified as phenolic amino acid
c- Tryptophan: as it contains indole ring so it is classified as
heterocyclic amino acid
7- Neutral heterocyclic amino acids:
a- Tryptophan: contains indole ring
b- Proline: In proline, amino group enters in the ring formation
being α-imino gp so proline is an α-imino acid
rather than α-amino acid
B- Basic amino acids: Contain two or more NH2 groups or nitrogen
atoms that act as base i.e. can bind proton.
At physiological pH, basic amino acids will be positively charged.
e.g.
a- Lysine
b- Arginine: contains guanido group
c- Histidine: is an example on basic heterocyclic amino acids

C- Acidic Amino acids: at physiological pH will carry negative

charge.
e.g. Aspartic acid (aspartate) and Glutamic acid (glutamate). see
structures in hand out.

Aspargine and Glutamine: They are amide forms of aspartate and

glutamate in which side chain COOH groups are amidated.
They are classified as neutral amino acids.
II- Classification according to polarity of side chain (R):

A - Non polar amino acids:

R is alkyl hydrophobic group which can’t enter in hydrogen bond
formation. 9 amino acids are non polar ( glycine, alanine, valine, leucine,
isoleucine, phenyl alanine, tryptophan, proline and methionine)

B - Polar amino acids: in which R contains polar hydrophilic group so

can forms hydrogen bond with H2O. In those amino acids, R may
contain:
1- OH group : as in serine, threonine and tyrosine
2- SH group : as in cysteine
3- amide group: as in glutamine and aspargine
4- NH2 group or nitrogen act as a base (basic amino acids ): as lysine,
arginine and histidine
5- COOH group ( acidic amino acids): as aspartic acid and glutamic
acid .
 Nonpolar (Hydrophobic) R Groups
Glycine (Gly) Methionine (Met)

Alanine (Ala)
Phenylalanine (Phe)

Valine (Val)

Proline (Pro)

Leucine (Leu)

Tryptophan (Trp)
Isoleucine (Ile)
 The side chain of Methionine includes a sulfur
atom but remains hydrophobic in nature.

 Phenylalanine is Alanine with an extra benzene

(sometimes called a Phenyl) group on the
end. Phenylalanine is highly hydrophobic and is found
buried within globular proteins.

Methionine Phenylalanine
 Proline is unique amongst the amino acids – its side
chain is bonded to the backbone nitrogen as well as to
the a-carbon.

 Because of this proline is technically an imino rather

than an amino acid.

 The ring is not reactive, but it does restrict the

geometry of the backbone chain in any protein where it
is present.
 Tryptophan is highly hydrophobic and tends to be
found immersed inside globular proteins.

 Structurally related to Alanine, but with a two ring

(bicyclic) indole group added in place of the single
aromatic ring found in Phenylalanine.

 The presence of the nitrogen group makes Tryptophan

a little less hydrophobic than Phenylalanine.
Polar (Hydrophilic) R Groups

Serine (Ser) Cysteine (cys)

Threonine (Thr) Asparagine (Asn)

Tyrosine (Tyr) Glutamine (Gln)

http://www.indstate.edu/thcme/mwking/amino-acids.html
Tyrosine is Phenylalanine with an extra hydroxyl (-OH)
group attached.
It is polar and very weakly acidic. Tyrosine can play an
important catalytic role in the active site of some
enzymes. Reversible phosphorylation of –OH group in
some enzymes is important in the regulation
of metabolic pathways

Serine and Threonine play important role in enzymes

which regulate phosphorylation and energy
metabolism.
Cysteine has sulfur-containing side group.The group
has the potential to be more reactive.It is not very polar.

Cysteine is most important for its ability to link to

another cysteine via the sulfur atoms to form a covalent
disulfide bridge, important in the formation and
maintenance of the tertiary (folded) structure in many
proteins.

COOH - CH- CH2 - HS SH- CH2- CH - COOH

NH2 NH2

S S
 Negatively Charged R Groups

Aspartic acid (Asp) Glutamic acid (Glu)

Two amino acids with negatively charged (i.e. acidic)

side chains - Aspartate (Aspartic acid) and Glutamate
(Glutamic acid).

These amino acids confer a negative charge on the

proteins of which they are part.
 Positively Charged R Groups

Lysine (Lys) Arginine (Arg) Histidine (His)

 Lysine and Arginine both have pKs around 10.0 and

are therefore always positively charged at neutral pH.

 With a pK of 6.5, Histidine can be uncharged or

positively charged depending upon its local
environment.
 Histidine has an important role in the catalytic
mechanism of enzymes and explains why it is often
found in the active site.
III- Nutritional classification:
1- Essential amino acids: These amino acids can’t be formed in the
body and so, it is essential to be taken in diet. Their deficiency
affects growth, health and protein synthesis.
2- Semiessential amino acids: These are formed in the body but not
in sufficient amount for body requirements especially in children.
Summary of essential and semiessential amino acids:
Villa HM = Ten Thousands Pound
V= valine i= isoleucine l= lysine l= leucine
A = arginine* H= histidine* M= methionine
T= tryptophan Th= threonine P= phenyl alanine
*= arginine and histidine are semiessential
3- Non essential amino acids: These are the rest of amino acids that
are formed in the body in amount enough for adults and children.
They are the remaining 10 amino acids.
 Essential Amino Acids in Humans

• Required in diet
• Humans incapable of forming requisite
carbon skeleton

Arginine* Lysine
Histidine* Methionine
Isoleucine Threonine
Leucine Phenylalanine
Valine Tryptophan
* Essential in children, not in adults
 Non-Essential Amino Acids in Humans

• Not required in diet

• Can be formed from a-keto acids by
transamination and subsequent reactions

Alanine Glycine
Asparagine Proline
Aspartate Serine
Glutamate Cysteine (from Met*)
Glutamine Tyrosine (from Phe*)
* Essential amino acids
IV- Metabolic classification: according to metabolic or
degradation products of amino acids they may be:

1- Ketogenic amino acids: which give ketone bodies .

Lysine and Leucine are the only pure ketogenic amino acids.

2- Mixed ketogenic and glucogenic amino acids: which

give both ketonbodies and glucose.These are: isoleucine,
phenyl alanine, tyrosine and tryptophan.

3- Glucogenic amino acids: Which give glucose. They

include the rest of amino acids. These amino acids by
catabolism yields products that enter in glycogen and glucose
formation.
29
 V. Classification Based on
Participation in Protein Synthesis.
• I. Non-Standard Amino Acids
• In addition to the 20 standard AAs, proteins may
contain non- standard (proteogenic) AAs, which are
normally components of proteins but created by
modification of the standard AAs.
• Among the non – standard AAs 4-OHproline, 5-
OHlysine where both are found in collagen, a fibrous
protein of connective tissues.
• 6 N –CH3lysine a constituent of myosin, a contractile
protein of muscle and γ-carboxy glutamate, which is
found in the blood clotting protein prothrombin.
30
 II. Non – Proteogenic Amino Acids

• These AAs occur in free or combined state, unlike in

proteins and play important roles in metabolism in
plasma, free AAs are usually found in the order of 10 to
100 μ mol/L, including many that are not found in
proteins.
• Citrulline is an important metabolite of L. arginine and
a product of Nitric oxide synthase, an enzyme that
produces nitric oxide an important signaling molecule.
• γ-aminobutyric acid - which acts as an inhibitory
neuro-transmitter
• D - Alanine : a component of vitamin B 5 pantothenic
acid
31
γ – amino butyric Brain, other animal tissues,
acid +
H3N functions as neurotransmitter.
COO-

+
D – Alanine H3N H Present in polypeptides,
C CH3
antibiotics & in some bacterial
COO-
cell walls.
Ornithine -
H
OOC NH3+
C In many tissues & an intermediate
H2
H2C C in Arginine synthesis.
C NH3+
H2

Citrulline H2N
metabolites of urea cycle
C O
HN
CH2
H2C
+
CH2
H3N
C H
COO-
32
 Specific amino acids give rise to
specialized products
• Tyrosine forms hormones such as thyroid hormones
(T3, T4), epinephrine, nor epinephrine and melanin
pigment.

• Tryptophan can synthesize a niacin vitamin.

• Glycine, Arginine and Methionine synthesize creatine.

• Glycine and Cysteine help in synthesize bile salts.

33
 Specific amino acids give rise to
specialized products
• Glutamate, Cysteine and glycine synthesize Glutathione
(GSH) which is important for several enzymes.

• Histidine changes to Histamine.

• Glycine is used for synthesis of heme porphyrins.

• Pyrimidines and purines used several amino acids for their

synthesis such as (Asp and Glu) for pyrimidine, and (Glu, Asp,
Gln and Ser) for purine synthesis.

34
 Specific amino acids give rise to
specialized
• Some amino acids such as (Glu and Cys) are used as
detoxifcants of specific substances.
• Methionine acts as active Methionine (δ – adensyl
– Methionine) to transfer methyl group to various
substances by transmethylation.

35
Amino acids properties

36
 Physical properties of AAs
• Optical isomerism:
• All amino acids have optical activities and rotate the
plane of polarized light & exist as levo or dextro
isomers except Gly.
• Optical activities depend on the pH & side chain.
• (Thr & Ile) have an additional asymmetric carbon
in their structure

37
 Physical properties of AAs
• Ultraviolet absorption:
• Aromatic amino acids which
are (Tyr, Trp, Phe) can
absorb UV light (280nm)
because they have aromatic
rings.
• This absorption is
frequently used for the
analytical detection of
proteins.
38
Nonionic and zwitterion forms of amino acids
The zwitterion predominates at neutral pH

Zwitterion = in German for „hybrid ion“

Week acid

Week base
Amphoteric properties of amino acids: that is they have
both basic and acidic groups and so can act as base or acid.
Neutral amino acids (monobasic, monocarboxylic) exist in
aqueous solution as “ Zwitter ion” i.e. contain both positive
and negative charge. Zwitter ion is electrically neutral and
can’t migrate into electric field.

Isoelectric point (IEP) = is the pH at which the zwitter ion is

formed. e.g IEP of alanine is 6
 Isoelectric P
• PI can be calculated for each amino acid with mono
amine and mono basic groups as follows:
PI: ( ½ PK1 + PK2)
PI can be calculated for mono amine
and di carboxylic group

42
Chemical properties of amino acids:
1- Reactions due to COOH group:
-Salt formation with alkalis, ester formation with alcohols,
amide formation with amines and decarboxylation
-2- Reactions due to NH2 group: deamination and
reaction with ninhydrin reagent.
Ninhydrin reagent reacts with amino group of amino acid
yielding blue colored product. The intensity of blue color
indicates quantity of amino acids present.
Ninhydrine can react with imino acids as proline and
hydroxy proline but gives yellow color.
 Ninhydrin Reaction

This strong oxidizing agent

bring about the oxidative
decarboxylation of amino
acid. The ammonia and
hydrindantin forme ninhydrin,
a purple pigment.
3- Reactions due to side chain (R):

1- Millon reaction: for tyrosine gives red colored mass

2- Rosenheim reaction: for trptophan and gives violet ring.

3- Pauly reaction: for imidazole ring of histidine: gives yellow to

reddish product

4- Sakagushi test: for guanido group of arginine and gives red

color.

5- Lead sulfide test (sulfur test): for sulfur containing amino acids
as cysteine give brown color.
 Peptides and Proteins
20 amino acids are commonly found in protein.
These 20 amino acids are linked together through “peptide bond
forming peptides and proteins (what’s the difference?).
- The chains containing less than 50 amino acids are called
“peptides”, while those containing greater than 50 amino acids
are called “proteins”.

Peptide bond formation:

α-carboxyl group of one amino acid (with side chain R1)
forms a covalent peptide bond with α-amino group of another
amino acid ( with the side chain R2) by removal of a molecule of
water. The result is : Dipeptide ( i.e. Two amino acids linked by
one peptide bond). By the same way, the dipeptide can then
forms a second peptide bond with a third amino acid (with side
chain R3) to give Tripeptide. Repetition of this process generates
a polypeptide or protein of specific amino acid sequence.
 Peptide Bond Formation

Ca COO- NH3+ Ca

amino acid 1 amino acid 2

 Peptide bond formation:

- Each polypeptide chain starts on the left side by free amino

group of the first amino acid enter in chain formation . It is
termed (N- terminus).
- Each polypeptide chain ends on the right side by free COOH
group of the last amino acid and termed (C-terminus).
Examples on Peptides:
1- Dipeptide ( tow amino acids joined by one peptide
bond):
Example: Aspartame which acts as sweetening agent being
used in replacement of cane sugar. It is composed of aspartic
acid and phenyl alanine.
2- Tripeptides ( 3 amino acids linked by two peptide bonds).
• Example: glutathione GSH which is formed from 3 amino
acids: glutamic acid, cysteine and glycine. It helps in
absorption of amino acids, protects against hemolysis of
RBC by breaking H2O2 which causes cell damage.
• Conjugation of drugs by GSH: is often a preliminary
reaction catalyzed by cytochrome P450, rendering
substances to be more polar and assist their excretion
 3- octapeptides: (8 amino acids) ( angiotensin II)
4- Nonapeptide:
Examples: Two hormones; oxytocine and vasopressin (ADH).

5- polypeptides: 10- 50 amino acids: e.g. Insulin & glucagon

hormones.

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