protein are most abundant molecule's

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2. Protein structure and function
The word protein comes from the Greek word proteos
meaning “primary”
The most abundant and important class of organic
compounds in our body, constituting more than half of
its cellular dry weight
Proteins are linear polymers of amino acids bound with
each other by peptide bond
Amino acids have carboxyl and amino groups bonded to
the α-carbon atom
A hydrogen atom and a side chain (R) are also attached
to the α-carbon atom
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3. 3
Functional protein
Amino acid structure
The side chain or R group distinguishes each
amino acid chemically.

4. Are the instruments by which genetic information is
expressed in the cell
Like carbohydrates they contain the elements carbon,
hydrogen and oxygen. In addition proteins contain
the element nitrogen and some times sulfur and
phosphorus
There are thousands of different kinds of proteins in
the cell, each carrying out specific function
determined by its gene. Thus, proteins are not only
the most abundant macromolecules but are
extremely versatile in their function 4

5. Play an important role in constructing the
structure of an organism. They are integral
components of cell membranes, skin, bone,
tendon, muscle and other tissues
Regardless of their function (biological activities)
all proteins are built from the same standard
amino acids
Qn: what is it, then, that gives one protein
enzyme activity, another protein hormone
activity and still another antibody activity? How
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6. Quite simply, proteins differ from each other :
 because each has a distinctive sequence of its
amino acid units ( the amino acids are alphabets
of protein structure, since they can be arranged
in an infinite number of sequences to make
almost infinite number of different protiens
proteins also differ from each other by:
 relative composition of each amino acid and
 total number of amino acid residues in chain
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7. • Under normal conditions, amino acids are
zwitterions (dipolar ions): amino group = -NH3
+ and
carboxyl group = -COO-
• Because of their neutrality, zwitterions cannot move
in an electric field
• 20 standard amino acids are found in proteins from
different life forms
• 19 of these amino acids are chiral (asymmetric)
• only the smallest amino acid, glycine, is achiral: it has
a second hydrogen atom attached to the α-carbon
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8. • when the amino group is found to the left of the
α-carbon, the amino acid is said to have an L-
configuration and if to the right a D-
configuration the amino acids found in proteins
have exclusively L- configuration
• The pH at which an amino acid, a peptide, or a
protein has zero overall charge after summing the
contributions of all the charges is called the
isoelectric point (pI).
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9. 9
a. When pH < pI, the overall charge is positive.
b. When pH > pI, the overall charge is negative.
c. When pH = pI, there is no overall charge. A peptide or
protein in such a case would not move in an electric
field applied during electrophoresis.

10. 10
20 Standard Amino Acids

11. Classification of Amino acids
The amino acids are generally grouped
according to the various characteristics of
their R groups. Accordingly:
Non-polar amino acids (hydrophobic)
Polar, uncharged amino acids
Polar, charged amino acids
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13. 13

14. 14

15. The following amino acids have additional ionizable
side chains (R groups) in addition to the common -α-
carboxyl group and - α-amino group:
 Lysine
 Arginine Basic a.as (have positive charge at neutral pH)
 Histidine
 Glutamic Acid Acidic a.as (have negative charge “ “)
 Aspartic Acid
Amino acids are ampholytes, i.e., they contain
both acidic and basic groups 15

16. Biological or Physiological Classification
A. Essential Amino Acids- amino acids which are not
synthesized in the body and must be provided in the
diet
 Nine amino acids: valine, leucine, isoleucine,
phenylalanine, tryptophan, methionine, histidine,
threonine and lysine
B. Non- Essential Amino Acids- that can be
synthesized in the body.
 The remaining eleven amino acids
C. Semi-essential amino acids: His and Arg
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17. Biochemical functions of proteins include
Catalysis: enzymes are proteins that direct and
accelerate several chemical reactions in the body
Structure: proteins like collagen that give shape and
mechanical strength
Source of energy
Movement : effected by cytoskeletons
Defense: through the action of antibodies
Regulation: the action of enzymes, hormones and
growth factors
Transport: like membrane proteins, hemoglobin,
Storage: such as in the case of ferritin
Stress response: as evidenced by heat shock proteins
that promote the correct refolding of damaged
proteins
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18. Based on their shape and solubility
A. Globular proteins: polypeptide chains are folded
to a nearly spherical shape , soluble in water
usually contain different types of secondary
structures
constitute the enzymes, oxygen carrying proteins,
hormones etc.
B. Fibrous proteins: polypeptide chains arranged in
to long cross-linked strands
usually contain a single type of secondary
structure
Include structural proteins like collagen, elastin,
keratin.
water insoluble
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19. Titration of amino acids
amino acids have two pKa values: one for the amino
group and another for the carboxyl group
the carboxyl group loses its protons first
after all protons on the carboxyl are lost, the amino
group starts to lose its protons and finally both the
carboxyl and amino groups will be deprotonated
Alanine has two dissociable groups: the carboxyl
group with pKa = 2.5 and the amino group with pKa =
9.5. A buffering zone is evident near each group’s pKa
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20. 20

21. 21
pI = isoelectric point
where all
molecules of amino
acids
are zwitterions

22. Amino acids with ionizable side chains have three pKa
values. Eg., The Titration of Histidine has three stages.
Histidine is an important buffer because of the pKR =
6 which is near the physiological pH.
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23. Peptides and proteins
amino acids are joined with each other by a peptide
bond formed by the condensation of the α-carboxyl
of one amino acid with the α-amino of another
amino acid (loss of H2O)
(no of amino acid)-1= no of H2O)
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carboxyl terminal
amino terminal
peptide bond

24. • when only a few amino acids are joined by
peptide bond they give oligopeptides (oligo = few)
• the linkage between several amino acids gives rise
to polypeptides (poly = many)
• proteins are molecules with weight more than
10,000 Da (Da = Dalton which is approximately
equal to the weight of one hydrogen atom)
• when they are in proteins amino acids are called
residues
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25. Protein structure
There are four levels of structural organizations
in proteins
1. primary structure
 refers to the linear sequence of amino acids
linked by peptide bonds to make up a protein.
2. Secondary structure
 describes the twisting of the polypeptide
backbone into regular structures that are
stabilized by hydrogen bonding.
 There are two types of secondary structure 25

26. 26
Fig showing the Schematic view of primary structure
Fig showing secondary structure of a protein

27.  α–helix - a coiled structure stabilized by
intrastrand hydrogen bonding between the
hydrogen of a peptide bond and an oxygen from
a peptide bond four residues away.
Eg., Keratin and Collagen helix
 β–pleated sheets -strands of peptides are linked
by interstrand hydrogen bonding in a zigzag
manner.
 May be parallel or anti-parallel
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side chain
α- carbon
β –pleated sheets
α–helix

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30. 3. Tertiary structure is formed by folding of
secondary structures into a large three-
dimensional organization that is mainly
stabilized by noncovalent interactions
hydrogen bonds, hydrophobic bond, electrostatic
bond and covalent disulfide bond.
Protein folding is the complex process by which
tertiary structures form within the cell.
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31. The side chains of highly polar amino acids tend
to reside on the exterior of proteins, where they
can form hydrogen bonds with water.
The side chains of nonpolar amino acids are
normally clustered in the interior of proteins to
shield them from water.
Eg:Myoglobin has tertiary structure
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32. 32
InteractionsThat MaintainTertiary Structure

33. 4. Quaternary structure -occurs in proteins that have
multiple polypeptide chains, called subunits.
In most cases, as in hemoglobin, the subunits are held
together by disulfide bond noncovalent interactions.
E.g. Hemoglobin has 4 chains, two of them are α and
two are β.
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34. Examples of proteins and their functions
I. Collagen
 25 % of our body’s protein
 Found in connective tissue such as tendons, cartilage,
the organic matrix of the bone and also in the cornea
 Made up of three left-handed helices which in turn are
joined into a right-handed super helix
 Hydrogen bonds between chains
 Gly-X-Y sequences are common in the helix; X is usually
proline or hydroxyproline and Y is any other amino
acid.
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35.  Hydroxyproline is the result of the hydroxylation
of an original proline that was present in a
protein
 there is also hydroxylysine which is involved in
forming covalent interactions with sugars
 Lysine forms covalent interactions between
chains
 The high frequency of glycine, with its small side
chain, allows the three collagen chains to pack
very tightly together for strength.
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36. Hydrogen bonding between the chains further
stabilizes the triple helix
the structure of collagen
Inability to hydroxylate proline and lysine results in a
weak collagen molecule
 vitamin C is essential for the activity of the
enzymes that hydroxylate proline and lysine
 deficiency of vitamin C gives rise to bleeding
gums, loss of teeth, bleeding under the skin (scurvy)
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II. myoglobin and hemoglobin
• myo refers to the muscles and hemo the blood
• oxygen is poorly soluble in the blood hence the
need for transporters
• iron binds oxygen strongly and reversibly
• but if it was present as free iron in the blood, it
would have led to the production of damaging
substances known as free radicals

38.  iron is found in the form of heme : attached
with an organic structure known as
protoporphyrin , which in turn is a small part
of the myoglobin or hemoglobin protein
 myoglobin binds one oxygen molecule and
hemoglobin can bind four molecules
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Myoglobin (Mb) Hemoglobin (Hb)
A monomeric protein, 153 aa
residues
A tetrameric protein α2 (141
aa residues each and β2 (146
aa residues each
Stores oxygen as a reserve
against oxygen deprivation
Transports O2 to the tissues
and returns CO2 and protons
to the lungs.
One O2 binding site in
muscle.
Four 4 O2 binding sites in
RBCs.
Oxygen affinity > Hb Oxygen affinity <Mb
Oxygen dissociation curve is
hyperbolic
Oxygen dissociation curve is
sigmoidal

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Hemoglobin

41. Myoglobin has a single chain and a single heme
while hemoglobin is a tetramer of two α and two β
subunits with four heme
The iron in the heme is bound with four nitrogens
of protoporphyrin
Additional two bonds are formed with oxygen and
a histidine residue from the protein backbone
 The iron in heme forms six bonds
Oxygen can bind only with the ferrous (Fe2+) form
of heme 41

42. If heme was found alone (without the protein
surrounding it), the ferrous form would have
been rapidly changed to ferric form
Methemoglobin is a form of hemoglobin in which
the iron atom is in the more oxidized ferric (Fe3+)
state rather than the normal ferrous (Fe2+) state.
not capable of binding O2.
Carbon monoxide binds with an affinity 250 X
that of oxygen and inactivates fero-hemoglobin
 in healthy people an average of 1 % of total
hemoglobin is found combined with CO
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43.  in smokers it could rise to 15 %
Fetal hemoglobin (HbF), which has slightly different
O2 binding properties from HbA, is composed of two
α- and two γ-globin subunits.
HbF has a higher affinity for O2 at all PO2 values than
HbA, which facilitates transplacental transfer of O2
from maternal blood to the fetal circulation.
Adult hemoglobin (HbA) has 2 α and 2 β chains
Myoglobin serves as a storage form of oxygen in
skeletal and cardiac muscles, where it binds O2 with
higher affinity than hemoglobin.
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44.  Hb transports oxygen cooperatively, i.e., the binding of
oxygen to one heme molecule increases the affinity of the
remaining three heme for oxygen 44
Hb binds O2 at the high PO2 (100 mm Hg) of the lung
and transports it to the peripheral tissues, where PO2 is
lower (~30 mm Hg) and O2 dissociates from Hb.

45. Unlike myoglobin, hemoglobin binds CO2, H+ and 2,3
– bisphosphoglycerate (2,3-BPG) in addition to
oxygen
Effects of carbon dioxide and protons
most of the CO2 produced by metabolism is changed
in the RBCs to bicarbonate
bicarbonate diffuses out of the RBC and travels to the
lung
the protons bind with Hb and make it release the
oxygen it was carrying
in the lungs, oxygen binds to protonated hemoglobin
and the protons are released
the released protons combine with bicarbonate to
give carbonic acid which gives CO2 that is exhaled
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CO2 + H2O <-----> H2CO3 <-----> H+ + HCO3
-
bicarbonate

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Exhaled

47.  The decrease in the affinity of hemoglobin for oxygen
caused by protons is known as Bohr effect
 Some CO2 binds hemoglobin to give carbamate
CO2 + Hb-NH2 <-----> H+ + Hb-NH-COO-
 The released protons decrease the affinity of
hemoglobin for oxygen 47
The Bohr effect is the
tendency of Hb to release
O2 in response to
decreased pH

48. The effect of 2,3 – bisphosphoglycerate (BPG)
• lowers the affinity of hemoglobin for oxygen
• fetal hemoglobin (HbF) binds BPG less strongly
than does adult hemoglobin (HbA)
• difference in affinity arising from the presence of
a gamma chain instead of a beta chain
 a fetus has a greater access to oxygen carried in
the blood than the mother
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49. Hemoglobinopathies
Sickle cell (HbS) is the most common
 caused by the substitution of valine for glutamic acid
in the β- chain
 deoxygenated hemoglobin becomes sticky and
precipitates .
 The RBC becomes sickle-shaped
 heterozygous individuals have resistance to malaria
Thalassemias
 deficiency in the synthesis of α or β chains
 Tissue hypoxia (O2 deficiency).
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Normal RBC
Sickled RBC

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Normal
versus
Sickle Cells
Normal Hemoglobin Val-His-Leu-Thr-Pro-Glu-Glu-
Sickle Cell Hemoglobin Val-His-Leu-Thr-Pro-Val-Glu-
•
6th residue

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