Amino acids, peptides and proteins

Proteins are the main macromolecules

in the living organisms
Collagen in Heamoglbin Immunoglob
bones form a and plasma ulins for
Contractile Enzymes and
framework for albumin
proteins in hormones are defense
the shuttle
deposition of
muscles drive controlling the
essential against
movement metabolism foreign
calcium molecules for
phosphate life particles
crystals

All proteins share the structure feature of being linear polymer of

amino acids

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 Amino acids
Amino acids contain a carboxyl group (COO-) and an amine group (NH2)) attached to
the alpha carbon atom and a distinct side chain called R, which is different from one
amino acid to another

More than 300

amino acids have
been recognized

Only 20 are
commonly found
as constituents of
mammalian
proteins and
coded in DNA

All amino A distinctive

Carboxyl Amino group side chain (R)
acids, except group (COOH) (NH2) bound to α-
proline, carbon atom
have 2
At physiologic pH (7.4)

Carboxyl or amino group are not free for any reaction

so the side chain define the function of the protein in
the cells

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 Classification of Amino acids

The amino acids are divided according to the •

number of carboxylate and amine groups and
:the type of side chain into
non-polar amino acids .1
Aromatic Amino Acids .2
neutral polar amino acids .3
Basic Amino Acids .4
Acidic Amino Acids .5

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Simplest amino acid is glycine (Gly, G) V shaped R group is valine (Val, V)

Second simplest AA is alanine (Ala, A)

Leucine (Leu, L)
Extra carbon before the R split in V
shape (Leucine. Leu)

Isoleucine (Ile, I)
It is an isomer of leucine
1st carbon in R group branches to
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have methyl and ethyl group

Methionine (Met, M) has a
thioether bond (C-S-C)
The first amino acid in any
polypeptide chain
Phenylalanine (Phe, F)
R group has one carbon
and then a phenyl ring
Aromatic
Tryptophan (Trp, W)
unusual R group, has two conjoined rings. First
ring has a CC double bond then bonded to
anitrogen that connects to another carbon in a
5 membered ring. A 6 membered phenyl ring
is a attached to this ring, aromatic
Proline (Pro, P) has 3 carbons in R group and
form a bond with nitrogen in AA
Give rigidity to any protein
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 Hydrophobic, non-polar, uncharged

Glycine Alanine Valine Leucine Isoleucine

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Methionine Tryptophan Phenylalanine Proline
 Non-polar
amino acids
Does not bind or give off •
protons or participate in
hydrogen or ionic bonds
Thought of oily or lipid- •
like property that
promotes hydrophobic
interactions
Tend to cluster together •
in the interior of the
.protein
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 Proline
The alpha-amine group is freenot and is •
substituted in all amino acids except for one,
. which is proline
it contains an imino group •
The unique geometry of proline contributes to •
the formation of the fibrous structure of
collagen

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 Serine (Ser, S)
R group has one carbons and ends w/ an alcohol
Cysteine (Cys, C)
R group has one carbons and ends
w/ an thiol
It forms a disulfide bond and form
cystine
Cystine
Threonine (Thr, T)
R group has a carbon w/ two
branches, a methyl and an
alcohol
Tyrosine (Tyr, Y)
R group has one carbon and than a benzene
ring, aromatic polar/uncharged
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 AsparagiNe (Asn, N)
R has one carbon and then a Glutamine (Gln, Q)
carbamate R group has two carbons and then a
carbamate

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 Hydrophillic, polar, uncharged
Have zero net charge at neutral pH

Threonine
Serine
Tyrosine
Cysteine Tyrosin
e
Participate in hydrogen bonding Lose H ion at alkaline pH

Asparagine Glutamine 13
 Aspartate (Asp, D) Glutamate (Glu, E)
R group has one carbon and a negatively R group has two carbons and a negatively
carboxylate anion carboxylate anion at neutral pH
At neutral pH

Acidic amino
acids, donate H+ at
neutral pH

Lysine (Lys, K)
/R group w/ a chain of four carbons ending w Arginine (Arg, R)
a positively charged ammonium substituent - R group w/ a chain of 3 carbons - nitrogen
carbon w/ two nitrogen attached, one nitrogen
is positively charged (ammonium ion)
substituent
Basic amino
acids, accept
H+ at neutral
pH

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 Histidine (His, H)
R group has a carbon and then a 5 membered
ring w/ two nitrogens. (carbon-nitrogen-
carbon-nitrogen-carbon)

Very weak basic

amino acids, accept
H+ at neutral pH

Depending on the
environment, it
carries positive
charge or neutral

Such as
Hemoglobin

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 Hydrophillic, polar, charged

Aspartate Lysine
Glutamate

Arginine Histidine

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Three and single letter code of amino acids

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 Unusual abbreviations
unusual three letters 4 unusual single letter (bold) 9

Isoleucine (Ile) • Phenylalanine (F) •

Tryptophane (Trp) • (Fenylalanine)
Asparagine (Asn) • TYrosine (Y) •
Glutamine (Gln) • Tryptophan (W) •
(TWyptophan)
AsparagiNe (N) •
Glutamine (Q) •
(Qtamine)
Lysine (K), near •
L
Aspartate (D), •
near to A
Glutamate (E), •
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GlutEmate
Examples of Nonprotein L-Amino Acids

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 Essential or non-essential amino acids

Failure to obtain
enough of even
1 of the 10 Unlike fat and
essential amino starch, the
acids, those that human body
Humans can The others we cannot does not store
make, results in
produce 10 of must be degradation of
excess amino
the 20 amino supplied in the body's acids for later
acids the food proteins— use—the
muscle and so amino acids
forth—to obtain must be in the
the one amino food every
acid that is day
needed

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 Non-essential
alanine, asparagine,
aspartic acid, cysteine,
glutamic acid, glutamine,
glycine, proline, serine
.and tyrosine
Essential
isoleucine, leucine, lysine,
methionine, phenylalanine,
threonine, tryptophan, and
valine

Semi-Essential Amino Acids: ■ The body can synthesize them, but not in
sufficient quantities, especially in the stage of growth, and it is preferred that
they be available in food. Like arginine and histidine

Tyrosine is produced from phenylalanine, so if the diet is

deficient in phenylalanine, tyrosine will be required as well

Plants, of course, must be able to make all the amino acids.

Humans, on the other hand, do not have all the enzymes required
. for the biosynthesis of all of the amino acids
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 Tofu

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Smelts
 The importance of amino acids
Glutamic acid plays an important role in the body's •
.metabolic processes
Glycine is involved in the synthesis of hemoglobin, •
creatine, bile acids, and glutathione, which plays an
important role in the oxidation and reduction processes
.that take place inside the body
Tryptophan provides the body with thiamine (B3), which •
is known as nicotinic or as niacin, as this amino acid has
.the ability to convert to this vitamin inside the body
Both phenylalanine and tyrosine are part of the •
.hormone adrenaline
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 .Aspartic acid and glycine are nucleotides synthesized •
Both arginine and glycine generate the compound •
creatine, which is stored in muscles as creatine
.phosphate
Tryptophan affects protein metabolism in the body •
and takes part in the formation of the hormone
.serotonin
Histidine is an essential component of the •
.antihistamine
Glycine helps rid the body of some toxic substances •
by chemically combining with them until they are
.excreted in the urine

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 Optical properties of amino acids
a chiral or optically active carbon atom
Except glycine has two hydrogen atoms

α-carbon can exist in two forms, designated

D and L, that are mirror images of each
other
The two forms in each pair are termed
stereoisomers, optical isomers, enantiomers

All amino acids found in proteins are of the

. L-configuration

D-amino acids are found in some antibiotics

. and in bacterial cell walls
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 The Genetic Code Specifies 20 L-α-
Amino Acids
Although more than 300 amino acids occur in nature, •
proteins are synthesized almost exclusively from the set
of 20 l-α amino acids encoded by nucleotide triplets
.called codons
While the three-letter genetic code could potentially •
accommodate more than 20 amino acids, the genetic
code is redundant since several amino acids are
.specified by multiple codons
Scientists frequently represent the sequences of •
peptides and proteins using one- and three letter
.abbreviations for each amino acid
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An amino acid is denoted by three letters, which are used to
designate the components and sequence of amino acids
.present in the polypeptide chains

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 Peptide
s
A peptide is the union of two or more amino •
. acids with peptide bonds ((- Co-NH

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 Amino Acid Sequence Determines Primary Structure

.Amino acids are linked together by peptide bonds •

The number and order of the amino acid residues in •
.a polypeptide constitute its primary structure
Amino acids present in peptides are called •
aminoacyl residues, and are referred to by replacing
the -ate or -ine suffixes of free amino acids with -yl
.(eg, alanyl, aspartyl, tyrosyl)
Peptides are then named as derivatives of the •
carboxy terminal aminoacyl residue. For example,
Lys-Leu-Tyr-Gln is called lysyl-leucyl-tyrosyl-
.glutamine
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 Amino Acid Sequence Determines Primary Structure

The -ine ending on the carboxy-terminal •

residue (eg, glutamine) indicates that its α-
carboxyl group is not involved in a peptide
.bond
Three-letter abbreviations linked by straight •
lines represent an unambiguous primary
.structure
Lines are omitted when using single-letter •
.abbreviations
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A peptide bond is formed via covalent binding of •
the Carbon atom of the Carboxy group of one
amino acid to the nitrogen atom of the amino
.group of another amino acid by dehydration
A polypeptide chain is a chain of amino acid •
.residues linked together by peptide bonds
The backbone of the polypeptide is given by the •
repeated sequence of three atoms of each residue
in the chain: the amide N, the alpha Carbon
.Calpha and the Carbonyl C
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Rotations in the chain take place about the •
bonds in the backbone, whereas the peptide
bond usually is unflexible as shown in the
.following figure

phi (φ) and psi (ψ)

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Draw the following tri peptide leucyl-tyrosyl-glutamine

Name the following tripeptide and identify the numbers of peptide bonds

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 The most important natural peptides
number of hormones are peptides that are •
chemical messages secreted by endocrine glands
and transported by blood in order to increase
.special activity in other tissues or organs
:Pancreatic hormones include •

Insulin: It regulates blood sugar and consists of •

two polypeptide chains linked together by a
disulfide bond
Glucagon It is the hormone that breaks down •
glycogen in the liver and consists of one
.polypeptide chain containing 29 amino acids 34
35
Hormones (posterior pituitary), including: Oxytocin It •
is a cyclic hormone consisting of 9 amino acids and
works to contract the muscles of the uterus during
childbirth and the contraction of the smooth muscles of
the mammary glands to secrete milk

Vasopressin A cyclic hormone consisting of 9 amino •

acids and works to increase blood pressure when
increasing its concentration, but its main task is to
reduce diuresis, and it is referred to as the urine control
.hormone 36
 Proteins
They are organic compounds formed by the •
linking of amino acids with each other by
means of peptide bonds forming a long chain
of molecules with a large molecular mass
ranging between forty thousand and forty
.million

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 Importance of proteins
.It is involved in the synthesis of all living cells •
It is considered essential in the human diet because •
it is the first source of amino acids for human
.growth
It is involved in the formation of many hormones •
such as insulin and growth hormone, as well as many
.enzymes such as glucokinase and phosphatase
The antibodies that protect the body against harmful •
.viruses and bacteria
.Maintains the osmotic pressure of the blood -5 •
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It transports vital compounds by blood from •
one tissue to another, such as albumin, which
.transports fatty acids and calcium
It plays an essential role in muscle contraction, •
. as the mucin protein

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 Classification of Proteins
:Simple proteins )a(
aminothe only yield they hydrolysisOn .acids
Examples are: albumins, globulins, glutelins,
.albuminoids, histones and protamines
:Conjugated proteins )b(
These are simple proteins combined with some non-
protein material in the body. Examples are:
nucleoproteins, glycoproteins, phosphoproteins,
.haemoglobins and lecithoproteins
:Derived proteins )c(
These are proteins derived from simple or conjugated
:proteins by physical or chemical means. Examples are
.denatured proteins and peptides 40
Comparison between Fibrous and Globular Protein

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42
Denaturation of Protein

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which

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 Protein structure
The twenty amino acids commonly found in proteins are •
.joined together by peptide bonds

The linear sequence of the linked amino acids contains •

the information necessary to generate a protein molecule
.with a unique three-dimensional shape

The complexity of protein structure is best analyzed by •

considering the molecule in terms of four organizational
levels, namely, primary, secondary, tertiary, and
quaternary
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Different Levels of Protein Structure
The primary structure is the sequence of residues in the •
.polypedptide chain
Secondary structure is a local regulary occuring structure •
in proteins and is mainly formed through hydrogen bonds
.between backbone atoms
So-called random coils, loops or turns don't have a stable •
.secondary structure
There are two types of stable secondary structures:Alpha •
.helices and beta-sheets
Alpha-helices and beta-sheets are preferably located at the •
.core of the protein56
57
 Primary structure of proteins
The sequence of amino acids in a protein is called the •
. primary structure of the protein
Understanding the primary structure of proteins is •
important because many genetic diseases result in
proteins with abnormal amino acid sequences, which
cause improper folding and loss or impairment of
.normal function
may be used to diagnose •
.or study the disease

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 Primary structure of proteins
(peptide bond)
Amino acids are joined covalently by peptide
bonds, which are amide linkages between the α-
carboxyl group of one amino acid, and the α-amino
.group of another
Peptide bonds are not broken by conditions that
denature proteins, such as heating or high
.concentrations of urea

Prolonged exposure to a strong acid or base at

elevated temperatures is required to hydrolyze
these bonds nonenzymatically
All amino acids sequences are read from
.the N- to the C-terminal end of the peptide
through acids amino manyof Linkage
unbranchedan in resultsbondspeptide
.chain called a polypeptide 59
 Characteristics of peptide bond
A partial double-bond character •
It is shorter than a single bond •
It is rigid and planar •
This prevents free rotation –
around the bond between the
carbonyl carbon and the nitrogen
. of the peptide bond
However, the bonds between the –
α-carbons and the α-amino or α-
carboxyl groups can be freely
rotated (although they are limited
by the size and character of the R-
. groups)
The peptide bond is generally a •
trans bond

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Secondary structure

The polypeptide forms

regular arrangements of
amino acids that are located
near to each other in the
.linear sequence
Ex. α-helix
β-sheet

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 α-helix
A spiral structure 
Tightly packed, coiled polypeptide backbone core 
With the side chains of the component amino acids 
extending outward from the central axis to avoid
interfering sterically with each other
Ex. Keratins, entirely α-helical and fibrous, in horns, 
hair, nails, hooves, stratum cornuem and claw
Rigidity is determined by the number of disulfide •
.bonds between the constituent polypeptide chains
Myoglobin, 80% helix α-helical so it is globular and •
flexible

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α-helix and hydrogen bonds
peptide-bond the between bonding hydrogenextensiveby stabilizedis α-helix
oxygen in -C=O and hydrogen in –NH that are part of the polypeptide backbone

The hydrogen bonds extend up the spiral from the carbonyl oxygen of one peptide bond
.to the -NH - group of a peptide linkage four residues ahead in the polypeptide

.Hydrogen bonds are individually weak, but they collectively serve to stabilize the helix

Each turn of an α-helix contains 3.6 amino acids. Thus, amino acid residues spaced three or
.four apart in the primary sequence are spatially close together when folded in the α-helix

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 β- sheet secondary structure
all of the peptide bond components are 
involved in hydrogen bonding

Polypeptide chain is extended 

appear β-sheetsof surfacesThe 

pleated," " ,are structurestheseand
therefore, "β-pleatedcalledoften
“.sheets

Looks like a broad arrow 

α-helix, the Unlike  are β-sheets
ortwo of composed peptidemore
chains (β-strands)
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β- sheet secondary structure
β-sheets the hydrogen bonds are perpendicular to the polypeptide backbone

:Parallel and antiparallel sheets

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 Tertiary structure
describes the packing of alpha-helices, beta-sheets •
with respect to each other on the level of one whole
.polypeptide chain
The tertiary structure of Chain B of Protein Kinase C •
.Interacting Protein

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 Tertiary structure
Four types of interactions cooperate in stabilizing the tertiary •
.structures of globular proteins
Disulfide bond .1
Covalent linkage formed from the sulfhydryl group (-SH) of –
each of two cysteine residues, to produce a cystine residue
Hydrophobic interactions .2
Amino acids with nonpolar side chains tend to be located in –
the interior of the polypeptide molecule, where they
associate with other hydrophobic amino acids
Hydrogen bonds .3
Amino acid side chains containing oxygen- or nitrogen-bound 
hydrogen, such as in the alcohol groups of serine and
threonine, can form hydrogen bonds with electron-rich
atoms, such as the oxygen of a carboxyl group or carbonyl
group of a peptide bond
.Enhances the solubility of the protein  67
 Tertiary structure
Ionic interaction.4
Negatively charged groups, such as the carboxyl group (-COO-) in the
side chain of aspartate or glutamate, can interact with positively
charged groups, such as the amino group (-NH3+) in the side
chain of lysine

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 Quaternary structure of proteins
.describes the spatial organization of the chains •
Protein may composed of single polypeptide (monomeric protein) •
Or more than one and may be are totally different •
Dimeric (two subunits [polypeptide]) –
Trimeric (three subunits) –
Multimeric (several subunits) –
is chains polypeptidedifferenttheof arrangementThe •
called quaternary structure
(for interactionsnoncovalentby togetherheld are Subunits •
and bonds, ionic bonds,hydrogenexample, hydrophobic
)interactions 69
 Quaternary structure of proteins
Subunits may either •
function independently of
,each other
or may work cooperatively, •
as in hemoglobin, in which
the binding of oxygen to
one subunit of the tetramer
increases the affinity of the
other subunits for oxygen
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