AMINO ACIDS AND

PRIMARY STRUCTURE
OF PROTEINS

Dexter F. Pajarito, MPH, PhD (in progress)

Instructor, Chemistry Department
Adventist University of the Philippines
 Functions of Proteins
• Functions as enzyme- biological catalyst
• Storage and Transport
• Support and Shape
• Mechanical work: movement of flagella
and separation of chromosomes.
• Play in decoding information in the cell.
• Hormones
• Antibodies.
IONIZATION OF AMINO ACIDS

pKa= -log Ka

pH= pKa
-When pH of the solution is below the
pKa, the protonated form
predominates.
H3+NCH-COO-
-When the pH s the solution is above
the pKa, the unprotonated form
predominates
H2NCH-COO-
 Nomenclature

• ine or ate = replaced with yl

• e from asparagine, glutamine, and
cysteine will be replaced with yl.
 α-helix
• Cumulative effect of H-bond within the a-
helix maintain the conformation
• H-bonding is stable in hydrophobic interior
of protein. (water do not enter, cant
compete with hydrogen bonding)
• Side chains are pointing outward
• Affected by the identity of the side chains.
 Example:
• Ala, fits well into helical conformation
• Gly, destabilizes a-helix structure
• Pro, least common residue in a-helix due
to its rigid cyclic side chain.
• Lacks H-atom in its amide nitrogen
• Cant fully participate in helical H-bonding
• Found at the end of the protein.
 TERTIARY STRUCTURE OF
PROTEINS

It is the overall three-dimensional

shape that results from the
attractive forces between amino
acid side chains (R groups) that
are widely separated from each
other within the chain.
ATTRACTIVE FORCES:

1. COVALENT DISULFIDE BONDS- strongest tertiary

structure interactions, results from the –SH of two
cysteine molecules reacting with each other to form
covalent disulfide.
2. ELECTROSTATIC ATTRACTION- also called SALT
BRIDGE. It involves amino acids with charged side
chains.
3. HYDROGEN BONDS- Results when two polar side
chains are close to each other (OH, NH2, COOH,
CONH2)
4. HYDROPHOBIC INTERACTIONS-Results when two
non-polar side chains are close to each other.
 QUATERNARY STRUCTURE OF
PROTEINS

-Highest level of protein organization

-It is found in proteins with two or more
polypeptide chains
-It involves the associations among the
separate chains in the oligomeric
proteins.
 Protein Denaturation and
Renaturation
• Denaturation-disruption in the native
conformation of protein with loss of biological
activity.
– Heat-will result to unfolding and loss of sec.
structure
– Normal proteins-stable at 50-60 degree C
– Chemicals: chaotropic and detergents
– Chaotropic- allow H2O to solvate nonpolar
group in the interior of proteins.
• Detergents (hydrophobic tails) penetrate
the protein interior and disrupting
hydrophobic interactions
 HYDROLYSIS OF
PROTEINS

-Peptide bonds are hydrolyzed

-Addition of strong acid or base
-Heated above normal temperature
-Due to the action of intestinal
enzymes
HEMOGLOBIN and MYOGLOBIN

Myoglobin-small monomeric protein that

facilitates the diffusion of oxygen in
vertebrates
-Responsible for oxygen in muscle tissues.

Myoglobin-member of globins
-interior: hydrophobic val, leu, ile, phe and
met
-Both are O2 binding-proteins
-contain 4 subunits (2 alpha and 2 beta
chains)
-Alpha chains- contain 141 AA each
-Beta chains- contain 146 AA each
-Heme-serves are prosthetic group.
Heme:
-Consist of tetrapyrole ring called
protoporphyrin IX complexed with iron.
-Bound iron (Fe2+)
 Hemoglobin

• More complex than Mb

• It poses quarternary structure
• Alpha and beta globin
X-ray diffraction revealed :

1. Alpha and beta chains

have identical tertiary
structures
2. Different vertebrates
have the same tertiary
structures
3. Alpha and beta chains of
hemoglobin are similar to
myoglobin. They have
the same capacity to bind
oxygen in their biological
functions
FACTS:

O2 is poorly soluble in water. For example, only around 3.2 mL O2

is soluble in 1 L blood plasma. By contrast, the protein
hemoglobin (Hb), contained in the erythrocytes, can bind a
maximum of 220 mL O2 per liter—70 times the physically soluble
amount.

Four of the six coordination sites of

the iron in hemoglobin are occupied
by the nitrogen atoms of the pyrrol
rings, and another is occupied by a
histidine residue of the globin (the
proximal histidine). The iron’s sixth
site is coordinatedwith oxygen in
oxyhemoglobin and with H2O in
deoxyhemoglobin.
 O2 TRANSPORT BY HEMOGLOBIN

-O2 is picked up from the lungs and forms oxyhemoglobin.

-It leaves the lungs saturated with O2 (@high partial O2
pressure)
-@ low partial O2 pressure, O2 separates from Hb, forming
reduced Hb or HHb.
So,
-If PO2 is high = Hb has higher affinity with O2 (98%
saturated)
-At lower PO2 = Hb has lower affinit for O2 (partially
saturated)
….four subunits of Hb act cooperatively in binding
oxygen….

T – taut/tense state, it resists the binding with O2 (lower

affinity)
R- relaxed state, binding is facilitated. (higher affinity)

•First O2 requires to break electrostatic attractions between

subunits.
•Conformational change happens that allows other subunits
to bind O2 more rapidly- known as POSITIVE
COOPERATIVITY
The sigmoidal shape of
hemoglobin's oxygen-
dissociation curve
results from cooperative
binding of oxygen to
hemoglobin.
 ALLOSTERIC MODULATORS

1.Increase in 2,3-DPG/BPG (RBC)

-allosteric effector. Lowers the affinity of
deoxyhemoglobin for O2
2.Proton Binding- known as Bohr effect
-lowers pH inside red blood cells.