OUR LADY OF FATIMA UNIVERSITY

College of Pharmacy

PHARMACEUTICAL BIOCHEMISTRY
PSMA 411
 ACTIVITY
• ON-LINE LECTURE
THROUGH ZOOM
• DURATION: __ HOUR

2
 UNIT OUTCOMES:

At the end of this unit, the students are

expected to:
• Characterize and differentiate biomolecules
• Analyze structure-function relationships
• Discuss the metabolic pathways of biomolecules
and identify the importance of the said concepts
in clinical practice
• Demonstrate understanding of the clinical
significance of these biomolecules.
 OUTLINE:
• Basic Concepts of Biochemistry
• Biomolecules
– Carbohydrates
– Lipids
– Nucleic acids
– Proteins
• Biosynthesis
• Functions
• Classification
• Physilogical significance
• Metabolic pathways of biomolecules
CHECKLIST
• Read study guide prior to
class attendance
• Read required learning
resources; refer to unit
terminologies for jargons
• Proactively participate in
discussions
• Participate in Canvas
discussion board
• Answer and submit
course unit tasks 5
REQUIRED READINGS

Ferrier, Denise R. Lippincott illustrated reviews

: biochemistry, 7th ed. Wolters Kluwer. 2017

Dr. Yogesh Ushir and Dr. Sudarshan Singh.

Pharmaceutical Biochemistry Everest
Publishing House. 2016

Lieberman, Michael. Mark's Essentials of

Medical Biochemistry : A clinical approach,
2nd ed. Wolters Kluwer 2015

Rodwell, Victor W. Harper's illustrated

biochemistry, 30th ed Mc Graw-Hill. 2015
6
Stoker, H. Stephen Biochemistry, 2nd ed .2015
 PROTEINS

complex, organic nitrogenous substances with

very high molecular weights, found in all plant and
animal cells, and consisting largely or entirely of
alpha-amino acids united in peptide linkage.

Amino acids
 Biomedical Importance of Proteins

1. Enzymatic catalysts 7. Control of Growth and

Differentiation
2. Transport and storage
8. Cell signalling
3. Coordinated motion
9. Hormones
4. Mechanical support
10. . Proteins are one of
5. Immune protection the major
6. Generation and components of
Transmission of Nerve biological membranes
 CLASSIFICATION OF PROTEINS
A. Classification Based on Composition, Physical
and Chemical Properties of the Protein
1. Simple Proteins
a. Albumin
b. Globulin
c. Glutelin
d. Prolamine
e. Albuminoid or Scleroprotein
f. Histone
g. Protamine
 CLASSIFICATION OF PROTEINS
2. Conjugated Proteins 3. Derived Proteins
a. Nucleoprotein a. Primary derived
b. Glycoprotein b. Secondary derived
c. Phosphoprotein
d. Chromoprotein
e. Lipoproteins
f. Metalloproteins
B. Classification Based on the Shape and Certain
Physical Characteristics of the Protein

1. Fibrous proteins
2. Globular proteins
C. CLASSIFICATION BASED ON BIOLOGIC
FUNCTIONS
1. Enzymes
2. Storage Proteins
3. Regulatory Proteins
4. Structural Proteins
5. Protective Proteins
6. Transport Proteins
7. Contractile or Motile
Proteins
 PROTEIN
STRUCTURES
1. Primary structure
2. Secondary structure
a. α-helix
b. β-sheets
3. Tertiary structure
4. Quaternary structure
PRIONS
Denaturation of proteins
 Destroy the higher structural levels of
protein

Renaturation of proteins
 The recovery of the protein from its
denatured state.
 AMINO ACIDS

- The building blocks of proteins

All amino acids have trivial or common names. In some cases, it is
derived from the source from which they were first isolated:
 ASPARAGINE
• First amino acid to be discovered
• Found in asparagus in 1806
 GLUTAMATE
• First isolated from wheat gluten
 TYROSINE
• First isolated from cheese  Name is derived from the Greek
“tyros” meaning “cheese”
 GLYCINE
• Greek “glykos” means “sweet”  So named because of its
sweet taste
Functions of amino acids

1. Building blocks of proteins

2. Precursor of various substances
a. Glycine – heme, purine, creatine

b. Glutamic acid - GABA

c. Phenylalanine & Tyrosine – thyroxine, epinephrine, melanin
d. Tryptophan – niacin, serotonin, melatonin, indole and skatole
e. Lysine – carnitine
 f. Histidine – Histamine
g. Lysine and Methionine – Carnitine

3. Source of energy
• 1 gram of Carbohydrates = 4 calories
•  1 gram of Fats = 9 calories
•  1 gram of Protein = 4 calories
Functions of amino acids
4. Special amino acids as components of certain
types of proteins..

Hydroxyproline & hydroxylysine – collagen

N-Methyllysine – Found in Myosin
Gamma-carboxyglutamic acid prothrombin
Desmosine (derivative of lysine) – elastin
Desmosine – Derivative of Lysine; Found in Elastin
N-Acetyllysine – Found in Histones that are
associated with chromosomes
Functions of amino acids
5. Phosphorylation and dephosphorylation of Ser, Thr
and Tyr play a major role in activation and
inactivation of enzymes.
6. Some amino acids or their derivatives act as
chemical messengers
e.g. GABA, serotonin
7. Several amino acids act as metabolic intermediates
e.g. Arg, citrulline, ornithine – urea cycle
8. Hormones can be derived from amino acids
9. Both D- and L-amino acids are present in
polypeptide antibiotics elaborated by
microorganisms.
 CLASSIFICATION OF AMINO ACIDS BASED ON
POLARITY

A. Amino Acids with NONPOLAR or

Hydrophobic R Groups
• Referred to as NEUTRAL amino acids
containing hydrocarbon R groups
• Interact poorly with water
• Play an important role maintaining the 3-
dimenstional structure of proteins.
Two Types of 2. ALIPHATIC
Hydrocarbon Side a. Glycine
Chains: b. Alanine
1. AROMATIC c. Valine
a. Phenylalanine d. Leucine
* Benzene Ring e. Isoleucine
b. Tryptophan f. Methionine
*Indole Ring g. Proline
 
Nonpolar or Hydrophobic Amino
Acids
1. Alanine
2. Glycine

3. Proline
4. Phenylalanine
5. Tryptophan
6. Methionine
• Source of SAM (S-
adenosylmethionine) = active
methyl donor
7. Leucine
8. Isoleucine
9. Valine
 1. Uncharged
Polar
3 TYPES OF
POLAR
2. Positively
AMINO
Charged Polar
ACIDS
3. Negatively
Charged Polar
 Amino Acids with
UNCHARGED POLAR R Groups

1. Hydroxyl-containing Amino
Groups:
a. Serine
b. Threonine
c. Tyrosine
2. Amide (CONH2) Derivatives of
Glutamate and Aspartate
a. Glutamine
b. Asparagine
3. Other:
a. Cysteine
 Lysine
Amino Acids
with
POSITIVELY
CHARGED Arginine
POLAR R
Groups (Basic
Amino Acids)
Histidine
 Amino Acids with 1. Negatively Charged R
NEGATIVELY
CHARGED POLAR R
Groups (Acidic Amino Acids)
Groups (Acidic Amino  Aspartic Acid
Acids)
 Glutamic Acid
 TEST FOR PROTEINS
NAME OF TEST REAGENT POSITIVE RESULT

Biuret Test 1% NaOH & Copper Violet Color

sulfate
Ninhydrin Test Ninhydrin reagent
Xanthoproteic Test HNO3 & 40% NaOH
Purple (Ruhemann’s purple)
–free amino group
Yellow –Imino acids
Yellow color

Millon’s Test Hg dissolved in HNO3 Yellow color

Hopkin’s-Cole Test Glyoxylic in glacial acetic Purple color on the surface

acid & H2SO4
Nitroprusside Test Nitroprusside in alkaline Red color
solution
Sakaguchi Test NaOH, α-naphthol & Red color
Bromine solution
NUCLEIC ACIDS
BIOMOLECULES: NUCLEIC ACID

Nucleic acids
Polymers of individual nucleotide monomer

• DNA
• RNA
BIOMOLECULES: NUCLEIC ACID

Nucleotides
Fundamental components:

phosphate group nitrogenous base

pentose sugar
BIOMOLECULES: NUCLEIC ACID
FUNDAMENTAL COMPONENTS:
• Nitrogenous base
– PURINES Guanine Adenine

– PYRIMIDINES
Cytosine Uracil Thymine
BIOMOLECULES: NUCLEIC ACID
Pentose sugar

Difference: Carbon 2 only difference is the

presence of a hydroxyl group
BIOMOLECULES: NUCLEIC ACID

DNA RNA
“Deoxyribonucleis acid” “Ribonucleic acid”
DOUBLE Strand SINGLE Strand
SUGAR: DEOXYRIBOSE SUGAR: RIBOSE
NITROGENOUS BASE: NITROGENOUS
Purine BASE:
 Guanine Purine
 Adenine  Guanine
Pyrimidine  Adenine
 Cytosine Pyrimidine
 THYMINE  Cytosine
 URACIL
BIOMOLECULES: NUCLEIC ACID

NUCLEOSIDES

A nucleoside
• named by changing the
nitrogen base ending to HO
-osine for purines and
–idine for pyrimidines.

158
BIOMOLECULES: NUCLEIC ACID

NUCLEOTIDES
A nucleoside phosphate
• named using the name
of the nucleoside
followed by
5’-monophosphate.

159
BIOMOLECULES: NUCLEIC ACID

N – base Sugar Nucleoside Nucleotide

Adenine Ribose Adenosine Adenosine PO4

Guanine Ribose Guanosine Guanosine PO4

Cytosine Ribose Cytidine Cytidine PO4

Uracil Ribose Uridine Uridine PO4
Thymine Ribose Thymidine Thymidine PO4
BIOMOLECULES: NUCLEIC ACID
Learning Check
Give the name and abbreviation of the
given figure and list its nitrogen base and
sugar.

guanine

ribose
 Guanosine 5’-monophosphate (GMP)
161
BIOMOLECULES: NUCLEIC ACID

Structural organization
• 1º sequence of the nucleotide
• 2º helical structure
• Stabilized by H – bond
• 3º Structure
• supercoiling
BIOMOLECULES: NUCLEIC ACID

Primary Structure of Nucleic Acids

163
BIOMOLECULES: NUCLEIC ACID
Example of RNA Structure

The primary structure

of RNA,
• is a single strand of
nucleotides with
bases A, C, G, and
U.

• is linked by
phosophodiester
bonds between
ribose and
phosphate.
Copyright © 2005 by Pearson Education, Inc.
Publishing as Benjamin Cummings
164
BIOMOLECULES: NUCLEIC ACID
2º helical structure
connect the 3'
hydroxyl group of
one pentose to the 5
H- bond carbon of another
pentose
phosphodiester bond
BIOMOLECULES: NUCLEIC ACID

"COMPLEMENTARITY"
• Adenine and Thymine
• Cytosine and Guanine
• Adenine and uracil (RNA)

• Hydrogen bonds

• # purines = # of pyrimidines
A + G = C + T
BIOMOLECULES: NUCLEIC ACID

Base pairs

• (A = T) MAJOR GROOVE
• ( C = G) MINOR GROOVE
BIOMOLECULES: NUCLEIC ACID

Give the complementary base sequence for

the matching strand in the following DNA
section:

—T —C —A —G —G —T —T —A—G —

—A—G—T—C—C—A—A—T—C—

168
BIOMOLECULES: NUCLEIC ACID

ANTIPARALLELISM
• In the chains,
each end of the
helix contains
the 5' end of
one strand and
the 3' end of
the other.
BIOMOLECULES: NUCLEIC ACID

DEGENERACY OF THE
GENETIC CODE
several codons may code for the same
amino acid.
1 AMINO ACID = 6 CODONS

DENATURATION

RENATURATION
BIOMOLECULES: NUCLEIC ACID

DNA FORMS
Z-DNA unique left – handed
helical structure

B – DNA most common / most

abundant
right - handed
double helices

A – DNA dehydrated B – DNA form

BIOMOLECULES: NUCLEIC ACID

CENTRAL DOGMA

Transcription
translation
replication REVERSE TRANSCRIPTION
BIOMOLECULES: NUCLEIC ACID

DNA synthesis

Conservative
Dispersive
Semiconservative
BIOMOLECULES: NUCLEIC ACID
Replication
Step 1: Initiation

Unwinding of the double helix:

Helicases
BIOMOLECULES: NUCLEIC ACID

Replication
Step 2: Priming
BIOMOLECULES: NUCLEIC ACID
Replication
Step 3: Elongation POLYMERIZATION
Assembly of 2 new strands of DNA

Leading Strand Lagging Strand

BIOMOLECULES: NUCLEIC ACID
Replication
POLYMERIZATION
DNA polymerase III
C 5’ new strand
G
T
C
A DNA polymerase I
A
3’ C
5’ T G DNA LIGASE
A
A
C
G
T
C
3’
BIOMOLECULES: NUCLEIC ACID

Replication

Step 4: Termination

Step 5: Proofreading and Correction

BIOMOLECULES: NUCLEIC ACID

Leading
Strand
Lagging Okazaki Replication
Strand fragments fork
BIOMOLECULES: NUCLEIC ACID
Key Enzymes in DNA replication:
Helicase Cleaves and unwinds short sections of
DNA ahead of the replication fork.

DNA Polymerase Serves 3 different functions:

1. Adds new nucleotides to 3’ end
of elongating strand.
2. Dismantles RNA primer. (I)
3. Proofreads base pairings (III)

DNA Ligase Catalyzes the formation of phosphate

bridges between nucleotides to join
Okazaki Fragments

Primase Synthesizes an RNA primer to begin the

elongation process.
BIOMOLECULES: NUCLEIC ACID
DNA polymerase
• removes the RNA Primer
• Pol I: implicated in DNA repair; has both 5'-
>3'(Polymerase) activity and 3'->5'
(Proofreading) exonuclease activity.
• Pol II: involved in replication of damaged DNA;
has 3'->5' exonuclease activity.
• Pol III: the main polymerase in bacteria
(elongates in DNA replication); has 3'->5'
exonuclease proofreading ability.
BIOMOLECULES: NUCLEIC ACID

• Topoisomerases
– Modify the newly synthesize DNA
– Topoisomerase type II
– Ex. DNA gyrase
• Target by QUINOLONES
BIOMOLECULES: NUCLEIC ACID

Transcription
• Synthesis of RNA from DNA
• produces the three basic types of RNA:
– messenger RNA
• Template of protein synthesis
• Carrier of codons
– ribosomal RNA
• Site of protein synthesis
– transfer RNA
• Contains anti – codon
BIOMOLECULES: NUCLEIC ACID

tRNA
Each tRNA
• has a triplet called an
anticodon that
complements a
codon on mRNA.
• bonds to a specific
amino acid at the
acceptor stem.
Anticodon

184
BIOMOLECULES: NUCLEIC ACID

• exons
-The informational DNA segments that make up
genes
• introns
-are the noncoding regions of the polypeptide.
During processing (splicing), the introns are
removed and exons soliced together to yield the
final mRNA
BIOMOLECULES: NUCLEIC ACID

–C –T –A –A –G –G –

B. –G –A –U –U –C –C –

186
 TRANSLATION
1.Initiation
Met Arg

2. Elongation
E P A

3. Termination Ribosome
BIOMOLECULES: NUCLEIC ACID

MUTATIONS
• POINT MUTATIONS
– Transitional
– Transversional

• FRAMESHIFT MUTATIONS
– Insertion
– Deletion mutations
BIOMOLECULES: NUCLEIC ACID

MUTATIONS
• POINT MUTATIONS
– Transitional
– Transversional
BIOMOLECULES: NUCLEIC ACID

Transitional Mutation
• Purine replaces another purine
• Pyrimidine replaces another Pyrimidine
– Eg. 5 – bromouracil
• Thymine analog
• Replace thymine in DNA

thymine
BIOMOLECULES: NUCLEIC ACID

Transitional Mutation
– 2 – aminopyrine
• Can replace adenine or guanine in DNA
• Cause bone marrow toxicity

adenine guanine 2 – aminopyrine

BIOMOLECULES: NUCLEIC ACID

Transversional mutation
• Purine replaces pyrimidine
• Results of point mutations

• SILENCE
– Codon containing the changed base codes for the
same amino acid

U C A UC U
(serine) (serine)
BIOMOLECULES: NUCLEIC ACID

Transversional mutation
• Purine replaces pyrimidine
• Results of point mutations

–MISSENSE
– Codon containing the changed base codes for the
diff amino acid

U C A C C A
(serine) (proline)
BIOMOLECULES: NUCLEIC ACID

Transversional mutation
• Purine replaces pyrimidine
• Results of point mutations

–NONSENSE
– Codon containing the changed base codes for STOP
codon
UAG
U C A UA A UGA
(serine) UAA
BIOMOLECULES: NUCLEIC ACID

2. Frameshift mutations
– where one or more bases is added or
removed.
– Can be caused by an aromatic compound
inserting between bases in stacked DNA.
This is called intercalation.
BIOMOLECULES: NUCLEIC ACID

DISEASES
DISEASE CONDITION
Xeroderma Pigmentosa Inability to repair tissue damage
NO EXONUCLEASE
Sickle Cell Anemia Valine replaces Glutamic acid
Thalassemia NONSENSE Mutation
Insufficient production of Hgb
Fanconi’s Anemia Short stature, aplastic anemia, induced by
mitomycin C
Fanconi’s Syndrome Proximal Tubule is Impaired
Lesch Nyhan Syndrome Deficiency in HGPRT ( Hypoxanthine-
guanine phosphoribosyl transferase)
 References:

Ferrier, Denise R. Lippincott illustrated reviews

: biochemistry, 7th ed. Wolters Kluwer. 2017
Dr. Yogesh Ushir and Dr. Sudarshan Singh.
Pharmaceutical Biochemistry Everest
Publishing House. 2016
Lieberman, Michael. Mark's Essentials of
Medical Biochemistry : A clinical approach, 2nd
ed. Wolters Kluwer 2015
Rodwell, Victor W. Harper's illustrated
biochemistry, 30th ed Mc Graw-Hill. 2015
Stoker, H. Stephen Biochemistry, 2nd ed .2015
222
ANY QUESTIONS?