

AMINO ACID CHEMISTRY

Definition.
Characters.
Classification:
Amino acids can be classified according to :
Number of amino and carboxyl groups in the amino
acid
Nutritional : either essential or non essential amino
acids
Metabolic: either glucogenicor ketogenicamino acids

Charge and polarity of side chain

 i) According to the number of amino and
carboxyl groups in the amino acid
 Neutral amino acids
 Acidic amino acids
 Basic amino acids
 Neutral amino acids
 1-Aliphatic amino acids:
 Glycine,Alanine, Valine , Leucine , Isoleucine.
 2) Aromatic amino acids:
 Phenyl alanine, Tyrosine, Tryptophan.
 3) Hydroxy amino acids:
 Serine, Threonine, Tyrosine.
 4) Sulphur-containing amino acids:
 Methionine, Cystiene , Cyst in
 5) Heterocyclic amino acids as histidine,tryptophan
 6) Imino acids as proline &hydroxyproline,
 Acidic amino acids
 Aspartic acid and Glutamic acid .
 Basic amino acids
 Arginine and Lysine
 Heterocyclic amino acids
 Histidine ,Tryptophan,Proline
andHydroxyproline
 ii Nutritional
Classification: : essential amino
acids) 1
 Phenylalanine , Treptophan,Histidin .
 Methionine , Threonine .
 Leucine , Valine , Isoleucine.
 Arginine, Lysine .
 non essential amino acids)
 2
 Glycine , alanine , serine , tyrosine , praline ,
hydroxyl praline , cystiene , cystin , aspartic
acid & glutamic acid
 Metabolic
Classification:iii
 1-Glucogenic amino acids
 as leucine 2-Ketogenic amino acid
 3-Both glucogenic and ketogenic amino acids
as
 Tyrosine, phenylalanine, tryptophan, lysine &
isoleucine
 According to charge and iv
polarity of side chain
 1-Hydrophobic, non polar uncharged amino acids
 as alanine,valine,leucine isoleucine &methionine
 2-Hydrophilic polar:

as serine,threonine a-Uncharged polar amino acid
 b-Charged polar amino acids
 Positively charged
 Negatively charged
 Properties of amino acids
 I. Physical properties:
 Soluble in water, strong acid and base.
 All are optically active due to presence of
asymmetric carbon atom except glycine.
 They have all the biological importance of proteins.
 They are amphoteric due to presence of 2 groups [-
COOH (acidic) –NH2 (basic)], so they react with both
acids and alkalies.
 * Iso-electric point [IEP]
 It is the pH at which the amino acid or proteins
carry . These Zwitter ionsve charge to form –
both +ve and ions are electrically neutral (do
not move in electric field) and are easily
precipitated. Each amino acid has its specific
I.E.P.
 Zwittern ion:It is the dipolar ion of
amphoteric compounds (amino acid and
proteins) produced when the pH of the medium
is at the I.E.P. It carries both +ve and –ve charges
and thus it is electrically neutral (does not move
in electric field).
 II. Chemical
propertiesgroup: NHReactions due to -
2

 A
 1-Reaction withacidsto formsalt
 2-Reaction with nitrous acidto liberate nitrogen. in all
amino acids except prolineand hydroxyproline.
 3-Reaction with acetyl chloride( acetylationreaction)
 Amino acid reacts with acetyl chloride to give acetyl amino
acid.
 4-Reaction with CO2to form carbaminocompounds
 5-Reaction with methyl iodide( methylation
reactions)
 6-Deamination of amino acids
 Oxidativedeamination: Produces α –keto aid and
NH3.
 Reductivedeamination: Produces fatty acid and
NH3.
 Hydrolyticdeamination: Produces hydroxyl fatty
acid and NH3
 Reactions due to COOH group:-B

 Reaction with strong alkaliesto form salt


Reaction withalcoholsto form esters


Decarboxylation reaction:

 To form primary amines

 e.g Histidine Histamine.
 Tryptophan Tryptamine.
 Serine Ethanolamine.

2Reaction
due to both
NH-Cand COOH
group
 Amino acids condense with each other by
COOH group at one amino acid with NH2of
other amino acid to form peptide bond. If 3
amino acids condense together they form
tripeptide .
 Reactions due to radical R:-D
 According to the side chain amino acids give colour

 reaction as:
 -sulfur test for sulfur containing a.a.
 -Xanthoproteic test for aromatic a.a.
 -Rosenheim test for tryptophan (indol ring).
 -Millon’s test for phenol group as tyrosine.
 -Ninhydrin reaction :all amino acids give blue colour
except proline which give yellow colour.
 PROTEIN
CHEMISTRYDefinition
 Proteins are organic complex nitrogenous compounds
of high molecular weight, formed of C, H, O, N [N=
16%]. They are formed of a number of amino acids
linked together by peptide linkage [-CO-NH-].
 The carboxylic group of the first amino acid units with
the amino group of the second amino acid and so on.
 Biological importance of
proteins
 They provide the body with nitrogen, sulfur, and some vitamins.
 Formation of enzymes and protein hormones.
 Formation of supporting structures in the body as bone, cartilage, skin,
nails, hair and muscles.
 They enter in the formation of buffer system of the blood.
 They enter in the formation of haemoglobin
 They include plasma proteins, which carry hormones, minerals and lipids
(in the form of lipoprotein complex).

They enter in formation of antibodies (immunoglobulins).
 General properties of proteins

Proteins are substances of high molecular weight.

Proteins form colloidal solution and having its same properties
as:

 Tyndall effect & Brownian movement


Proteins are non dialyzable due to their large molecules.

Proteins are amphoteric which liable to react with acid and alkali. Each protein
has its own isoelectric point. Protein acts as a buffer solution which resists the
change of its pH by addition of acid or alkali.

 •Denaturation
 Denaturation of protein
 it is a change in native state (physical, chemical, and biological
properties) of proteins without destruction of their peptide
linkages ,but destruction of secondary bonds leading to
unfolding protein molecule.
 Denaturatingagents:

Physical:High temperature, high pressure, X-ray, ultraviolet
rays-mechanical agitation., organic alkalies: Strong acids, strong
Chemical

 solvents, heavy metals.

 Results of denaturation:
 Physical:

Decrease solubility, Iincrease viscosity and can not be crystallized.
 Chemical:

Unfolding of the protein molecule.

Destruction of some subsidiary hydrogen bonds.

Exposure of some groups as (SH) of cystiene.
 Biological:

Loss of activity, if it is hormone or enzyme.

Loss of antigen antibody reaction (allergicmanifestation). Easily
digested

.
 Folloculation of proteins

It is a precipitation of denaturated protein at
its I.E.P.

This folloculation is dissolved again by
changing pH from the I.E.P by addition of acid
or alkali (reversible).
 Coagulation of prteins
 Boiling of the folloculated protein changing it
to coagulum.
 This coagulum can not dissolved again even
by changing the pH (irreversible).
 Precipitation of proteins
 Proteins are precipitated from solution by many ways:
 At I.E.P.
 By high concentrations of neutral salts as ammonium
sulfate, Mg sulfate, Na chloride.
 By heavy metals e.g. silver nitrate, lead acetate.
 By strong acids e.g. trichloro acetic acid (TCA),
phosphotungestic acid, picric acid.
 By organic solvents which are miscible with H2O e.g. ethyl
alcohol, methyl alcohol, acetone….
 Fractionation of proteins
 Precipitation by neutral salts
 Electrophoresis:
 It is the migration of proteins in an electric field.

Proteins in alkaline medium migrate to anode.

Proteins in acidic medium migrate to cathode.
 When a sample of plasma proteins is subjected to electrophoresis, albumin
will be the fastest in migration followed by α –globulin, β –globulin, γ –
globulin.
 This method is used to diagnose any abnormalities in plasma proteins.
 Ultracentrifugation:Centrifugation of proteins at very high
speed according to molecular weight.
 Chromatography & dialysis.
 Classification of proteins
 Prpteins can be classified on the basis of their
solubility, shape,biological functions,or chemical
composition
 1-Classification of proteins according to their solubility:
 Proteins soluble in H2O,or other biological solvents
(Albumin –globulin-Histones –Protamin -prolamin –
glutelins)
 Proteins not soluble in most protein solvents
[albuminoids] as nail and hair.
 According to their
shape:-2
 A-Globular proteins : axial ratio is more than
10,more stable as keratin & myosin in muscles.

 B-Fibrous proteins : axial ratio is less than 10 ,

less stable as albumin & globulin.
 3-according to their biologic
functions :
 Enzymes: e.g. dehydrogenases, kinases
 Storage proteins: ferritin , myoglobin
 Regulatory proteins: DNA-binding protein, peptide hormones
 Structural proteins: collagen
 Protective proteins: clotting factors , immunoglobulins
 Transport proteins: hemoglobin , plasma lipoproteins
 Motile proteins: actin, tubulin
 according to their
chemical -4composition
On hydrolysis, they produce : Simple
proteins-A
 as albumin ,globulins, glutellin only amino acids
 Prolamines,protamines,histones,
 albuminoids(scleroproteins).
 albuminoids (scleroproteins)
 They are fibrous proteins.
 Insoluble in H2O, dilute acids and alkali, and all neutral
solvents.
 Not digested by proteolytic enzymes.
 Found in animal tissues and having supportive and
protective function as keratin ,elastin ,collagen &

 gelatin.
 (compound protein)Conjugated proteins-B
 These are formed of protein part and non protein
part.

 According to non protein part, they are divided into:

 1-Glycoproteins and Mucoproteins:
 Protein conjugated with carbohydrate e.g.
 certain hormones [FSH, LH, TSH] &
Immunoglobulins
 IMMUNOGLOBALINS (IGs)
 Globulins are mainly formed in reticulo-endothelial
system in macrophages and lymphocytes.
 Immune system is divided into :
 B-cells (Bone marrow): concerned with circulating
humeral antibodies.
 T-cells (Thymus glands): concerned with cell
mediated immune response as graft rejection,
hyypersensitivity reactions and defense against
malignant cells and viral infection.
 Lipoproteins:
 Protein conjugated with lipids either
[phospholipids-triglyceride-cholesterol] e.g.
Chylomicrons –VLDL –LDL –HDL.
 It is the transport form of lipids in blood.
 Phosphoproteins:
 Protein conjugated with phosphoric acid thruogh
hydroxylic group of serine, threonine &tyrosine
 Casienogen is an example for phosphoproteins (the
main protein of milk ).

 Metalloproteins
 Proteins conjugated with metals e.g.
 Ceruloplasmin = protein + Cu.
 Insulin = protein + zinc.
 Chromoproteins:
 Hemoglobin containing Fe-porphyrin (red color).
 Chlorophyll containing Mg-porphyrin (green
color).
 Flavoproteins: These are enzymes containing
FMN, FAD (yellow color).
 Nucleoproteins:
 Proteins conjugated with nucleic acids e.g. Histone
associated with DNA in chromosomes.
 Derived proteins-C
 These are the denaturated or hydrolytic products of
 either simple or conjugated proteins.
 : 1-Primary protein derivatives
 These results from alteration of proteins from its native state
without hydrolysis:
 Metaproteins: Due to the effect of acid or alkali e.g.:
 Acid or alkali metaprotein.
 Gelatin [denaturated collagen].
 Coagulated proteins: Due to the effect of heat e.g.
 Coagulated albumin and globulin.
 2-Secondary protein derivatives:
 These are the hydrolytic priducts of proteins
 Proteoses:
 Result from partial hydrolysis of proteins.
 Peptones:
 Result from further hydrolysis of proteases.
 Soluble in H2O.

 •Peptides:
 Resulting from further hydrolysis of peptones.

 • Amino acids
 Structure of proteins:
 Proteins are formed of a large number of amino
acid linked togther by peptide bonds (polypeptide
chain).
 There are four orders of protein structures
 Primary structure of Proteins:
 Referred to the number, type and sequence of
amino acids in the polypeptide chain.
 Any change in one of amino acids in polypeptide
chain produces a physiological defect.
 The main bond in this structure (peptide bond) –
CO-HN-
 Secondary Structure of Proteins
 The polypeptide chain will be folded to give a specific
conformational form which may be :Helix-

 The α
 The α-helix is a common secondary structure encountered in proteins
of the globular class. The formation of the α-helix is spontaneous and
is stabilized by H-bonding between amide nitrogens and carbonyl
carbons of peptide bonds spaced four residues apart. This orientation
of H-bonding produces a helical coiling of the
 peptide backbone such that the R-groups lie on the exterior of the
helix and perpendicular to its axis.
 pleated Sheets-ββ-sheets are composed of 2 or
more different regions of stretches of at least 5-10
amino acids. The folding of the polypeptide
backbone aside one another to form β-sheets is
stabilized by H-bonding between amide nitrogens
and carbonyl carbons. β-sheets are said to be
pleated. This is due to positioning of the α-carbons
of the peptide bond which alternates above and
below the plane of the sheet.
 hydrogen bonds or disulfide bonds It formed by
between two extended polypeptide chains or
pleated -. βbetween two regions of single
chainsheets exist in two forms: parallel (the
adjacent chains are aligned in the same direction
with respect to N-terminal and carboxy terminal
residues) and antiparallel(the two chains are
arranged in opposite direction ) .
 Loop sheets:-
 Half of the residues in a typical globular protein
are present in α helices or β pleated sheets, the
remainder reside in loop or coil conformation
which form the antigen-binding sites of antibodies.
 These loops should not be confused with random
coils which are biologically unimportant
conformations of denatured proteins
 -supersecondary structures (motifs):
 α helices or β pleated sheetsform recognizable
supersecondary motifs,such as:
 β–α –β: ( two strands of βsheets connected by αhelix
 β –hair pin-: two antiparallelβsheets connected by
short regions of loop.structural motifhelix (HTH) is a
major -turn-

 helixα . It is composed of two DNAcapable of binding

amino acidsjoined by a short strand of helices
 Tertiary Structure of Proteins
 Tertiary structure refers to the complete three-
dimensional structure of the polypeptide units of a
given protein. Secondary structures of proteins are
coiled to constitute distinct structure called
Domains arefundamental functional domain.
three dimentional structural units of Therefore,
tertiary structure also polypeptides. describes the
relationship of different domains to one another
within a protein molecle
 The core of a domain is built from combinations of
secondary structural elements (motifes).
 The interactions of different domains is governed
by several forces: These include hydrogen bonding,
hydrophobic interactions, electrostatic interactions
and van der Waals forces.
 Forces Controlling Tertiary Protein
StructureHydrogen Bonding:-1
 Polypeptides contain numerous proton donors and
acceptors both in their backbone and in the R-
groups The environment in which proteins are
found also contains H-bond donors and acceptors
of the water molecule. H-bonding, therefore, occurs
not only within and between polypeptide chains but
with the surrounding aqueous mediumof the amino
acids.
 Hydrophobic Forces:-2
 Proteins are composed of amino acids that contain
either hydrophilic or hydrophobic R-groups. It is
the nature of the interaction of the different R-
groups with the aqueous environment that plays the
major role in shaping protein structure.
 The hydrophobicity of certain amino acid R-groups
tends to drive them away from the exterior of
proteins and into the interior. This driving force
restricts the available conformations into which a
protein may fold.
 Electrostatic Forces:-3
 Formed between oppositely charged groups in the
side chains of amino acid. e.g.
 ε-amino group of lysine and carboxyl group of
aspartate.
 Lysine –NH3+…………….-OOC-aspartate
 van der Waals Forces:-4van der Waals repulsive and
attractive
 There are both forces that control protein folding.
Attractive van der Waals forces involve the interactions
among induced dipoles that arise from fluctuations in the
charge densities that occur between adjacent uncharged
non-bonded atoms. Repulsive van der Waals forces involve
the interactions that occur when uncharged non-bonded
atoms come very close together but do not induce dipoles.
The repulsion is the result of the electron-electron repulsion
that occurs as two clouds of electrons begin to overlap.
 5-Disulphide bonds:
 Formed between 2 cystieneresidue, it connect 2
polypeptide chain or 2 sections in one chain. It is
covalent bond.
 Quaternary Structure of ProteinsMany proteins
contain 2 or more different polypeptide chains that
are held in association by the same non-covalent
forces that stabilize the tertiary structures of
proteins. Proteins with multiple polypetide The
proteins. oligomericchains are monomer -structure
formed by monomerinteraction in an oligomeric
protein is known as quaternary structure.
 Oligomeric proteins can be composed of multiple
identical polypeptide chains or multiple distinct
polypeptide chains. Proteins with identical Proteins
oligomers.-homosubunits are termed containing
several distinct polypeptide chains are , the
Hemoglobin. oligomers-heterotermed oxygen
carrying protein of the blood, contains two α and
two β subunits arranged with a quaternary structure
in the form, α2β2. Hemoglobin is, therefore, a
hetero-oligomeric protein.
 Protein folding
 Protein folding is the process by which a string
of amino acids (the chemical building blocks of
protein) interacts with itself to form a stable
three-dimensional structure during production
of the protein within the cell. The folding of
proteins thus facilitates the production of
discrete functional entities, including enzymes
and structural proteins, which allow the various
processes associated with life to occur
 mportance of folding protein moleculesIessential
for the production of
 Protein folding is structures that can perform
particular functions prevents inappropriate Also
it in the cell .in that folding interactions between
proteins,hides elements of the amino acid
sequence which if exposed would react non-
specifically with other proteins.
 Protein misfolding
 Under favorable conditions, most proteins have
no problem quickly folding to their native
structures. However, there are some proteins
which appear unable to fold without the presence
of other helper proteins, called chaperones. In the
absence of chaperones, these proteins will fail to
achieve their native state and instead may
associate with otherunfolded polypeptide chains
to form large aggregate structures.
 Inappropriate folding is one way in which a
protein imbalance may arise –the misfolded
protein may be nonfunctional or suboptimally
functional, or it may be degraded by cellular
machinery
 Protein misfolding diseases
 In many cases, misfolded proteins are
recognised to be undesirable by a group of
proteins called heat shock proteins, and
consequently directed to protein degradation
machinery in the cell. This involves conjugation
to the protein ubiquitin, which acts as a tag that
directs the proteins to proteasomes, where they
are degraded into their constituent amino acids.
 Hence many protein misfolding diseases are
characterised by absence of a key protein, as it has
been recognised as dysfunctional and eliminated by
the cell’s own machinery. Diseases caused as a
consequence of misfolding, include cystic fibrosis &
other disease .
 In addition, some cancers may be associated with
misfolding. Many protein misfolding diseases are
characterised not by disappearance of a protein but
by its deposition in insoluble aggregates within the
cell.
 Diseases caused by protein aggregation include
Alzheimer’s disease (deposits of amyloid beta
and tau), Type II diabetes (depositis of amylin),
Parkinson’s disease (deposits of alpha
synuclein),
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