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Proteins: Polymers of Amino Acids
• 20 different amino acids: many combinations
• Proteins are made in the RIBOSOME
Amino Acid Chemistry
20 different types
R
amino
NH2
Ca
acid
COOH
H
R1
NH2
Ca
R1
COOH
H
NH2
R2
NH2
Ca
COOH
Ca
H
R2
CO NH
Ca
H
H
Amino acid
Polypeptide
Protein
COOH
Amino Acid Chemistry
R
amino
NH2
Ca
acid
COOH
H
The free amino and carboxylic acid groups have pKa’s
NH3+
NH2
COOH
pKa ~ 9.4
COO-
pKa ~ 2.2
R
+NH
3
Ca
COO-
H
At physiological pH, amino acids are zwitterions
Amino Acid Chemistry
Note the axes
Also titratable
groups in side chain
Amino Acids with Aliphatic R-Groups
Glycine
Gly - G
2.4
9.8
Alanine
Ala - A
2.4
9.9
Valine
Val - V
2.2
9.7
Leucine
Leu - L
2.3
9.7
Isoleucine
Ile - I
2.3
9.8
pKa’s
Amino Acids with Polar R-Groups
Non-Aromatic Amino Acids with Hydroxyl R-Groups
Serine
Ser - S
2.2
9.2
~13
Threonine
Thr - T
2.1
9.1
~13
8.3
Amino Acids with Sulfur-Containing R-Groups
Cysteine
Cys - C
1.9
10.8
Methionine
Met-M
2.1
9.3
Acidic Amino Acids and Amide Conjugates
Aspartic Acid
Asp - D
2.0
9.9
Asparagine
Asn - N
2.1
8.8
Glutamic Acid
Glu - E
2.1
9.5
Glutamine
Gln - Q
2.2
9.1
3.9
4.1
Basic Amino Acids
Arginine
Arg - R
1.8
9.0
12.5
Lysine
Lys - K
2.2
9.2
10.8
Histidine
His - H
1.8
9.2
6.0
Aromatic Amino Acids and Proline
Phenylalanine
Phe - F
2.2
9.2
Tyrosine
Tyr - Y
2.2
9.1
Tryptophan
Trp-W
2.4
9.4
Proline
Pro - P
2.0
10.1
10.6
Hierarchy of Protein Structure
• 20 different amino acids: many combinations
• 8 essential
Primary Structure
The order of amino acids: Protein sequence
Secondary Structure
Local conformation, depends on sequence
Tertiary/Quaternary Structure
Overall structure of the chain(s) in full 3D
Binding Classification of Proteins
 Structural- other structural proteins
 Receptors- regulatory proteins, transmitters
 Toxins- receptors
 Transport- O2/CO2, cholesterol, metals, sugars
 Storage- metals, amino acids,
 Enzymes- substrates, inhibitors, co-factors
 Cell function- proteins, RNA, DNA, metals, ions
 Immune response- foreign matter (antigens)
Classification
 Essential amino acids:
 There are amino acids that cannot be synthesized in
the body.
 They must be taken in diet.
 Their deficiency affects growth , health and proteins
synthesis.
Half essential amino acids
 These amino acids are synthesized in the body in
amount enough for adults , but not for growing
children.
 Arginine
 Histidine
Arginine is very popular among athletes and
bodybuilders because it is required in muscle
metabolism – maintaining the nitrogen balance,
and helping with weight control since it facilitates
the increase of muscle mass, while reducing
body fat.
Non essential amino acids
 These are the rest of amino acids which are
synthesized in the body , mostly from carbohydrates,
in amount enough for adults and growing children.
Metabolic classification
 Ketogenic amino acids: which gives both ketone
ketones bodies. Leucine is the only ketogenic amino
acids.
People with liver and kidney problems can also
benefit form L-Leucine supplementation because it
can enhance liver protein synthesis and improve
breathing ability and quality of sleep for those with
kidney disorders.
Finally, L-Leucine may lower blood sugar levels
and normalize and control insulin release and
insulin function. Because of this, diabetics may find
L-Leucine a helpful addition to their disease
management program.
Glucogenic and ketogenic amino
acids
 Which give both ketone bodies and glucose are:
 Phenylalanine
 Tyrosine
 Tryptopohan
 Lysine
 Isoleucine
Functions of amino acids
 Body peptides and proteins: E.g plasma proteins ,
tissue proteins, enzymes etc
 Hormones: Some hormones are amino acids
derivatives. E.g thyrosine and catecholamines.
 Amines: Some amino acids give corresponding amines
by decarboxylation e.g histidine gives histamine which
is vasodilator.
Cont.
 Neurotransmitters: Some amino acids, glutamate acts
as neurotransmitters.
 Detoxification: Some amino acids are used
detoxification reaction e.g glycine
 Health and growth: Essential amino acids support
growth in infants and maintain health in adults.
physical properties
 Solubility: Soluble in water, dilute acids , alkalies and
ethanol.
 Optical activity: Optically active because they contain
asymetric carbon.
 Melting point: High ionic forces. Tm 200˚C.
Chemical properties
 Peptide bond formation.
 Properties of R group.
Proteins
 Proteins are molecules having a very high molecular
weight ,ranging from 5,000 to several million.
 The term protein is applied to describe molecules
greater than 100 a.a
 Molecules contain less than 100 a.a are termed :larger
polypeptides.
Functions
 Enzymes :all enzymes are proteins
 Transport : of small molecules and ions e.g
 1. Hemoglobin is a carrier for oxygen.
 2. lipoproteins , are carriers of lipids.
Structural proteins
 Cell membrane : Glycoproteins
 Skin and bones e.g collagen
Hormonal regulation
 Some hormones are protein in nature e.g insulin.
 Cellular receptors that recognise hormones are
proteins.
Defence mechanism
 Antibodies (immunoglobulins) are proteins in nature.
 Keratin found in skin and tissues is proteins that act
against mechanical and chemical injuries.
Cont.
 Blood clotting : coagulation factor
 Storage: Ferritin ,which is a storage form of iron.
 Control of genetic expression: activator receptors and
many regulators of genes are protein in nature.
Conformation of proteins
 Every protein in its native state has a 3-dimensional
structure.(primary, secondary, and tertiary),which is
known as conformation . Conformation is essential for
the function of each protein. Any change in
conformation may lead to disease.
Primary proteins
 It is a order (arrangement) of amino acids in the
polypeptide chain.(chains).
 Covalent bond.
 Free NH3 and CooH terminals.
 The arrangement of amino acids in each protein is
determined by the genetic information present in
DNA.
Secondary proteins
 Hydrogen bonds
 Two forms alpha and beta form.
a Helix
Left-hand
a helix
Right-hand
a helix
Tertiary structure
 Two types:
 Fibrous : which is an extended form e.g keratin
,collagen and elastin.
 Globular proteins: which is a compact form and
folding of polypeptide chain e.g myoglobin.
Quaternary structure
 Many proteins are composed of several polypeptide
chain .Each polypeptide chain is called subunits.
 E.g insulin : 2 subunits
 Lactate dehydrogenase enzyme :4 subunits
 Globin of haemoglobin:4 subunits.
Denaturation of proteins
 Def : protein denaturation mean unfolding and loss of
secondary ,tertiary and quaternary structure.
 1.denaturation does not affect primary structure i.e
not accompained by hydrolysis of peptide bonds.
 2. denaturation may be reversible( in rare cases)
Effect of protein denaturation
 Loss of biological activity : insulin looses its activity
after denaturaion.
 Denaturation proteins are often insoluble.
 Denaturation protein are easily precipitated.
Denaturation factor
 Heat
 Organic solvents
 Detergent
 Mechanical mixing
 Strong acids and bases
 Heavy metals.
 Enzymes
 Repeated freezing and thawing
Classification of proteins
 Simple proteins: On hydrolysis they give only amino
acids.
 Conjugated proteins: give amino acids and non
proteins (prosthetic group).
 Derived proteins:
 1. primary derived proteins : denatured protein
 2.secondary derived proteins: product of hydrolysis of
simple and conjugated proteins.
Simple proteins
 Albumin and globulin
 Scleroproteins : include keratin ,collagen
,elastin,reticulin.
Alpha keratin
 Found in hair ,nail , enamel of teeth ,and outer layer of
skin.
 Rich in cysteine
 Insoluble due to high content of hydrophobic amino
acids
collagen
 Present in skin ,bones , tendons, and blood vessels.
 Collagen may be present as a gel e.g in extracellular
matrix or in vitreous humor of the eye.
collagen diseases
 Scurvy; it is due to deficiency in a ascorbic acids
(vitamin c).
 Ascorbic acids acts as coenzyme in hydroxylation
reaction of proline and lysine.
 Symptoms: abnormal bone development ,bleeding ,
loosing of teeth and swollen gums.
Cont.
 Osteogenesis imperfecta:
 1. It is a genetic disorders lead to weak bones and
skeletal deformities.
 2. It is due to mutation in the gene that code for α –
chain for collagen.
 Ehlers-Danlos syndrome:
 Genetic disorder lead to connective tissues disease
 Symptoms : stretchy skin and loosed joints.
Elastin
 It is a connective tissue proteins.
 Rubber –like, stretched several times
 Present in lungs , the walls of large blood vessels and
elastic ligaments.
Conjugated proteins
 On hydrolysis ,they give protein part (apoproteins)
and nonproteins part(prosthetic group)
phosphoproteins
 These are protein conjugated with phosphate group.
 Phosphate group is attached to –OH group of serine
(phosphoserine) or threonine(phosphothreonine)
present in protein part. E.g
 Caseine :one of the milk protein
 Vitellin: present in egg yolk.
 Phosphoenzyme: phoephorylation and
dephosphorylation.
lippoproteins
 These are proteins conjugated with lipids
 Plasma proteins and cell membrane.
 Helps water insoluble lipids to transport in blood
 Helps water insoluble substance to pass through cell
membrane .
Glycoproteins and proteoglycans
 These are proteins conjugated with carbohydrates in
varying amount .i.e 2 to 15 sugar units.e.g blood group,
enzyme and mucin
 Proteoglycans contain long unbranched chains of
sugar units more than 50 units. E.g cell membrane
nucleoproteins
 These are proteins conjugated with nucleic acid (DNA
or RNA ).
 1. chromosomes: proteins conjugated with DNA .
 2. Ribosomes; proteins conjugated with RNA.
Metalloproteins
 Proteins conjugated with metals
 Mettaloproteins containing iron: The iron may be in
the form of heme or nonheme iron.
 Ferritin : is the storage form of iron ,present in liver
,spleen, bone marrow and intestinal cells.
 Transferrin. Is the iron carrier protein in the plasma.
 Hemosiderin :iron toxicity (over dosage) as in case of
repeated blood transfusion.