PROTEIN

SYNTHESIS
LUCY MENG’ANYI
 Lesson Outline
1. Nucleus
• Introduction
• Structure of the nucleus

2. Genetics

3. Protein Synthesis
• Introduction
• Ribonucleic Acids (RNA)
• Gene Expression: Central Dogma
• Steps of protein synthesis
• Transcription
• Translation
4. Growth Factors
5. Cell Death
6. Cell Adaptation
7. Cell Degeneration
8. Cell Aging
9. Stem Cell
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 Nucleus
• The most prominent and the largest cellular organelle.

• It has a diameter of 10 µ to 22 µ and occupies about 10% of total volume of the cell.

• Is present in all the cells in the body except the red blood cells.

• Is located in the center of the cell.

• It is mostly spherical in shape.

• However, the shape and situation of nucleus vary in some cells

• The cells with nucleus are called eukaryotes and those without nucleus are known as
prokaryotes.

• Presence of nucleus is necessary for cell division.

• Most cells have only one nucleus i.e. uninucleated with the exception of few like skeletal
muscle cells which are multinucleated.

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 Structure of Nucleus

• Is covered by a nuclear membrane and

contains many components.

• Major components are

• nucleoplasm,
• chromatin and
• nucleolus.

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 Structure of the Nucleus

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 Nuclear Membrane

• Is double layered and porous allowing the

nucleoplasm to communicate with the
cytoplasm.

• The outer layer of nuclear membrane is

continuous with the membrane of
endoplasmic reticulum.

• Has pores for exchange of substances

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 Nucleoplasm
• Is a highly viscous fluid that forms the ground substance of the
nucleus.

• It is similar to cytoplasm

• Surrounds chromatin and nucleolus.

• It contains a dense fibrillar network of proteins called the

nuclear matrix

• The nuclear matrix forms the structural framework for

organizing chromatin

• Also contains many substances such as nucleotides and enzymes.

• Nuclear hyaloplasm is the soluble liquid part of nucleoplasm

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 Chromatin
• Is a thread-like material made up of large molecules of
DNA.

• The DNA molecules are compactly packed with the help of

a specialized basic protein called histone.
• Hence chromatin is referred to as DNA-histone complex.
• It forms the major bulk of nuclear material.

• DNA is a double helix which wraps around the central

core of eight histone molecules to form the fundamental
packing unit of chromatin called nucleosome.

• Nucleosomes are packed together tightly with the help of

a histone molecule to form a chromatin fiber.

• Just before cell division, the chromatin condenses to

form chromosome.
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 Chromatin
• Nucleosome: DNA + Histones (8 proteins)

• Chromatin fiber: several nucleosomes packed

together

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 Chromosomes
• Rod-shaped nuclear structure

• Carries a complete blueprint of all the hereditary

characteristics of that species.

• Formed from a single DNA molecule coiled around

histone molecules.

• Each DNA contains many genes

• Normally, the chromosomes are not visible in the

nucleus under microscope.
• They are only visible under a microscope during cell
division, because DNA becomes more tightly packed just
before cell division.
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 Chromosomes cont.…
• Normal human cells contain 23 pairs of chromosomes.

• 22 pairs, called homologous chromosomes , are sets

containing genetic information that controls the same
characteristics or functions.

• The 23rd pair contains sex (X and Y) chromosomes.

• The composition of these chromosomes determines gender: XX
produces a genetic female; XY, a genetic male.

• In the female, the genetic activity of both X

chromosomes is essential only during the first few weeks
after conception.
• Later development requires just one functional X chromosome.
• The other X chromosome is inactivated and appears as a dense
chromatin mass called a Barr body (sex chromatin body) that’s
attached to the nuclear membrane in the cells of a normal
female.
• In the cells of a normal male, who has only one functional X
chromosome, the Barr body is absent.
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 A chromosome is a highly coiled and folded DNA
molecule that is combined with protein molecules.

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 Functional types of chromosomes
1. Autosomes
• Are the chromosomes present in somatic cells.
• The number of autosomes in a cell is fixed and is
expressed as 2n or diploid number.

2. Sex chromosomes
• Are present in the sex cells
• Are responsible for determining the sex of an
individual

3. Supernumerary or redundant chromosomes

• Are found in eukaryotic cells but their occurrence is
quite uncommon
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 Nucleolus
• Is a small, round granular structure of the nucleus.

• Each nucleus contains one or more nucleoli.

• Contains RNA and some proteins, which are similar to

those found in ribosomes.

• RNA is synthesized by five different pairs of

chromosomes and stored in the nucleolus.
• Later, it is condensed to form the subunits of ribosomes.

• All the subunits formed in the nucleolus are transported

to cytoplasm through the pores of nuclear membrane.

• In the cytoplasm, these subunits fuse to form ribosomes,

which play an essential role in the formation of proteins.
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 Functions of Nucleus
1. Control of all the cell activities that include:
• metabolism,
• protein synthesis,
• growth and reproduction (cell division)

2. Synthesis of RNA

3. Formation of subunits of ribosomes

4. Sending genetic instruction to the cytoplasm for protein

synthesis through messenger RNA (mRNA)

5. Control of cell division through genes

6. Storage of hereditary information (in genes) and

transformation of this information from one generation
of the species to the next
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 Nucleic Acids
• Are an important class of macromolecules found in
all cells and viruses

• Are called nucleic acids because they were first

discovered in the nucleus of cells.

• With improved technology, they were further

discovered in the mitochondria, chloroplasts, and
cells that have no nucleus, such as bacteria and
viruses.

• The two main types of nucleic acids are:

• Deoxyribonucleic acid (DNA) and
• Ribonucleic acid (RNA).
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 Deoxyribonucleic Acid (DNA)
• Is a nucleic acid that carries the genetic information

• It forms the chemical basis of hereditary characters.

• It contains the instruction for the synthesis of proteins in the

ribosomes.

• Gene is a part of a DNA molecule.

• Is present in the nucleus (chromosome) and mitochondria of the cell.

• The DNA present in the nucleus is responsible for the formation of

RNA.

• RNA regulates the synthesis of proteins by ribosomes.

• DNA in mitochondria is called non-chromosomal DNA.

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 Structure of DNA
• Double stranded complex nucleic acid.
• Formed by:
• Deoxyribose- sugar
• phosphoric acid/ Phosphate and
• four types of organic nitrogenous bases: Nucleotide
• Purines:
• Adenine (A)
• Guanine (G)
• Pyrimidines:
• Thymine (T)
• Cytosine (C)

• Each DNA molecule consists of two polynucleotide chains, which

are twisted around one another in the form of a double helix.

• The two chains are formed by the sugar deoxyribose and

phosphate.
• These two substances form the backbone of DNA molecule.

• Both chains of DNA are connected with each other by some

organic
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 STRUCTURE OF DNA cont..
• DNA strands are arranged in such a way that both
are bound by specific pairs of bases.
• The adenine (purine) of one strand binds specifically with
thymine (pyrimidine) of opposite strand.
• Similarly, the cytosine (pyrimidine) of one strand binds
with guanine (purine) of the other strand.
• Each molecule of DNA has equal number of adenine and thymine
residues (A =T) and equal number of guanine and cytosine
residues (G=C).
• This is known as Chargaff’s rule.
• Each human DNA molecule contains a specific sequence of more than
100 million base pairs.
• The base pair sequence is identical in all the DNA of one individual
and different from that of all other individuals.
• DNA forms the component of chromosomes, which
carries the hereditary information.
• The hereditary information that is encoded in DNA is
called genome.

• Each DNA molecule is divided into discrete units

called genes
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 STRUCTURE OF DNA cont..
A. Double helical
structure of DNA;

B. Magnified view of the

components of DNA.

A = Adenine (purine),

C = Cytocine (pyrimidine),

G= Guanine (purine)

P =Phosphate,

S = Sugar,

T = Thymine (pyrimidine).

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 GENE
• Is the functional unit of DNA.

• Is a portion of DNA molecule that contains the message or code for

the synthesis of a specific protein from amino acids.

• It is like a book that contains the information necessary for protein

synthesis.

• Thus, each gene forms the code word for a particular protein to be
synthesized in ribosome (outside the nucleus) from amino acids.

• Three successive base pairs in DNA are together called a triplet or a

codon on mRNA.

• Each codon codes or forms code word (information) for one amino
acid.
• There are 20 amino acids and there is a separate code for each amino acid.
• For example, the triplet CCA is the code for glycine and GGC is the code for proline.

• Thus, each gene forms the code word for a particular protein to be synthesized in
ribosome (outside the nucleus) from amino acids.
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 Genetic Disorders
• Disorders that occur because of abnormalities
in an individual’s genetic material (genome).

• Genetic disorders are either

• hereditary disorders or
• due to defect in genes

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 Causes of Gene Disorders
• Occur due to two causes:
1. Genetic variation: Presence of a different
form of gene

1. Genetic mutation: an alteration or a change

in nature, form, or quality.
• Refers to change of the DNA sequence within a
gene or chromosome of an organism, which results
in the creation of a new character.

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 Classification of Genetic Disorders

• Are classified into 4 types:

1. Single gene disorders

2. Multifactorial genetic disorders

3. Chromosomal disorders

4. Mitochondrial DNA disorders.

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 Single Gene/Mendelian/Monogenic
Disorders

• Occur because of variation or mutation in one

single gene.

• Examples include:
• Sickle cell anemia and
• Huntington’s disease

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 Multifactorial Genetic/Polygenic Disorders
• Caused by combination of environmental
factors and mutations in multiple genes.

• Examples are:
• Coronary heart disease,
• Alzheimer’s disease,
• Arthritis and
• Diabetes.

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 Chromosomal Disorders
• Are genetic disorders caused by abnormalities in
the chromosomes.

• They are also called chromosomal abnormalities,

anomalies or aberrations.

• Often result in genetic disorders which involve

physical or mental abnormalities.

• Are caused by numerical or structural

abnormalities
• Hence classified into two types as per these causes.
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 Classification of Chromosomal Disorders
1. Structural abnormalities of chromosomes:
• Which lead to disorders like:
• Chromosome instability syndromes
• A group of inherited diseases which cause malignancies

2. Numerical abnormalities of chromosomes

• Are of two types:
• Monosomy: due to absence of one chromosome from
normal diploid number E.g. Turner’s syndrome, which is
characterized by physical disabilities

• Trisomy: due to the presence of one extra

chromosome along with normal pair of chromosomes in
the cells. E.g. Down syndrome, which is characterized
by physical disabilities and mental retardation
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Clinical Features of Turner’s syndrome

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 Mitochondrial DNA Disorders
• Are caused by the mutations in the DNA
of mitochondria (non chromosomal DNA).
E.g.
• Kearns-Sayre syndrome: Neuromuscular
disorder characterized by myopathy,
cardiomyopathy and paralysis of ocular
muscles

• Leber’s hereditary optic neuropathy:

disease characterized by degeneration of
retina and loss of vision.

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 Some Common Genetic Diseases

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 Protein Synthesis introduction
• Hundreds of Amino Acids link together to make
one Protein

• Remember as per slide 20 there are 20 types of

amino acids, some we can make, and some we can’t

• There are infinite combinations of amino acids

• They can be hundreds or thousands monomers long

• These long chains are called polypeptide chains

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 Amino Acids

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 Protein Synthesis introduction cont..
• Protein synthesis is the process in which a cell
makes protein based on the message contained
within its DNA.
• However:
• DNA is only found in the nucleus
• Proteins are only made outside the nucleus – in the
cytoplasm.

• Then how do the many different messages within

the DNA molecule get to the many ribosomes
outside the nucleus hence aiding in protein
synthesis?
• A molecular cousin of DNA – RNA – is used to carry
these messages.
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 Ribonucleic Acid (RNA)
• Is a nucleic acid that contains a long chain of
nucleotide units.

• It is similar to DNA but contains ribose instead

of deoxyribose.

• It is formed from DNA

• The function of RNA is to carry messages from

the DNA (in the nucleus) to the ribosomes (in the
cytoplasm).
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 Structure Of RNA
• Each RNA molecule consists of a single strand of
polynucleotide unlike the double stranded DNA.

• Each nucleotide in RNA is formed by:

• Ribose – sugar.
• Phosphate.
• One of the following organic bases:
• Purines:
• Adenine (A) Nucleotide
• Guanine (G)
• Pyrimidines:
• Uracil (U)
• Cytosine (C).

• Uracil replaces the thymine of DNA and it has a similar

structure as of thymine.

• Due to the single stranded structure Chargaff’s rule is not

obeyed, i.e. there is no specific relation between purine and
pyrimidine contents.
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 Structure Of RNA

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 Differences between the structure of
DNA & RNA
• RNA is single stranded while DNA is double
stranded

• The ribose sugar in RNA contains an additional

oxygen atom compared with DNA.

• Instead of the base thymine, RNA contains the

base uracil.
• This means that adenine will always pair up with uracil
during the protein synthesis process.

• Chargaff’s rule is not obeyed in RNA

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 Types of RNA
• There are three types of RNA:
1. Messenger RNA (mRNA)
• It is synthesized in the nucleus and enters the cytoplasm to
participate in protein synthesis.
• Carries the genetic code of the amino acid sequence for
synthesis of protein from the DNA to the cytoplasm

2. Transfer RNA (tRNA):

• Is responsible for decoding the genetic message present in
mRNA
• There are about 20 species of tRNA corresponding to 20 amino
acids present in protein structure.

3. Ribosomal RNA (rRNA)

• Is present within the ribosome and forms a part of the structure
of ribosome.
• It is responsible for the assembly of protein from amino acids in
the ribosome.

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 Protein Synthesis
• Synthesis of a specific protein requires transcription of
a gene’s DNA into RNA and translation of RNA into a
corresponding sequence of amino acids.
• This is referred to as the Central Dogma of molecular biology

• Occurs in TWO steps:

1. Transcription:
• the genetic information from a strand of DNA is copied into a
strand of mRNA

2. Translation:
• the mRNA, with the help of the ribosome, forms a chain of
amino acids (eventually forming a protein) based on the
information contained on the mRNA.

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 DNA Structure for recap

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 Transcription
• The word transcription means copying.
• It occurs within the nucleus
• If we were to use the analogy of a secretary for better understanding:
• A secretary converts shorthand notes or an audio recording into a letter, memo, circular
etc.
• In other words, the same information is transformed from one form or format to
another.

• In cells, transcription involves the transfer of information from DNA’s base

sequence into the complementary base sequence of mRNA

• Only DNA and mRNA are involved in transcription.

• Each three base sequence specifying a particular amino acid on the DNA gene
is called a triplet, and the corresponding three-base sequences on mRNA are
called codons.
• The form is different, but the same information is being conveyed.
• E.g. you can have a sequence of DNA triplets as AAT-CGT-TCG, and the related codons on
mRNA would be UUA-GCA-AGC

• Remember in DNA molecule

• Then remember that Uracil replaces the thymine in an RNA molecule

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 Transcription cont..
• Since DNA is a macromolecule, it cannot pass through the
pores of the nuclear membrane and enter the cytoplasm.

• A region of DNA unwinds and the two strands separate,

however, only that small portion of the DNA will be split
apart.
• The triplets within the gene on this section of the DNA molecule
are used as the template to transcribe the complementary strand
of RNA

• A codon is a three-base sequence of mRNA, so-called

because they directly encode amino acids.

• mRNA then enters the cytoplasm from the nucleus and

activates ribosomes resulting in protein synthesis.

• The formation of mRNA from DNA is facilitated by the

enzyme RNA polymerase.
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 Translation
• It is the process by which protein synthesis occurs in the ribosome of
the cell under the direction of genetic instruction carried by mRNA
from DNA.
• Or, it is the process by which the mRNA is read by ribosome to produce a
protein.

• Here we can use the analogy of a translator:

• A translator takes words in one language and restates them in another language.
• In the translation phase of protein synthesis, the language of nucleic
acids (base sequence) is “translated” into the language of proteins
(amino acid sequence).

• Translation involves the role of tRNA and rRNA

• mRNA moves out of nucleus into the cytoplasm & is attached to

polysomes (a group of ribosomes)

• The sequence of codons in mRNA are thus exposed and recognized by

the complementary sequence of base in tRNA.

• It occurs in the cytoplasm

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 Translation sequence of events
1. mRNA moves out of nucleus into the cytoplasm & is
attached to polysomes (a group of ribosomes)

2. The sequence of codons in mRNA are thus exposed and

recognized by the complementary sequence of base in
tRNA (anticodon).

3. According to the sequence of bases in anticodon,

different amino acids are transported from the
cytoplasm into the ribosomes by tRNA that acts as a
carrier

4. With the help of rRNA, the protein molecules are

assembled from amino acids.

5. Protein synthesis occurs in the ribosomes which are

attached to rough endoplasmic reticulum
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 Overview of gene expression.

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Portion of an RNA molecule, showing three RNA “codons”—CCG, UCU, and
GAA—which control attachment of the three amino acids proline, serine, and
glutamic acid, respectively, to the growing RNA chain.
 Growth Factors
• These are proteins which act as cell signaling
molecules like cytokines and hormones

• They bind with specific surface receptors of

the target cell and activate proliferation,
differentiation and/or maturation of these
cells

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 Examples of Growth Factors
Growth Factor
Platelet derived growth factor (PDGF)
Colony stimulating factors (CSF)
Nerve growth factors (NGF)
Neurotropins
Erythropoietin
Thrombopoietin
Insulin like growth factors (IGF)
Epidermal growth factor
Basic fibroblast growth factor
Myostatin
Transforming growth factors (TGF)
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Comments
Present in keratinocytes & fibroblasts. It inhibits growth of hair follicles &
cancer cells
Present in blood vessels. It is concerned with the formation of new blood
vessels
present in skeletal muscle fibers. It
controls skeletal muscle growth
Present in transforming cells (cells undergoing differentiation) & in large
quantities in tumors & cancerous tissue. TGF is of two types:
• TGFα secreted in brain, keratinocytes & macrophages. It is concerned
with growth of epithelial cells and wound healing
• TGFβ secreted by hepatic cells, T lymphocytes, B lymphocytes,
macrophages & mast cells. When the liver attains the maximum size in
adults, it controls liver growth by inhibiting proliferation of hepatic cells.
TGFβ also causes immunosuppression. 49
 Cell Death

• Occurs by two distinct processes:

1. Apoptosis

2. Necrosis.

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 Apoptosis
• This is the natural or programed death of a cell under
genetic control.

• It is also called ‘cell suicide’ since the genes of a cell

play a major role in the death

• It is a normal phenomenon and is essential for normal

development of the body.

• Usually it does not produce inflammatory reactions in

the neighboring tissues.

• The purpose of apoptosis is to remove unwanted cells

without causing any stress or damage to the
neighboring cells.

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 Functional Significance of Apoptosis
1. Plays a vital role in cellular homeostasis.
• About 10 million cells are produced everyday in human body by mitosis.
• An equal number of cells die by apoptosis.
• Apoptosis removes the auto aggressive T cells and prevents autoimmune
diseases.

2. Useful for removal of a cell that is damaged beyond repair by a

virus or a toxin
a) A cell that looses the contact with neighboring cells or basal lamina in the
epithelial tissue dies by apoptosis.
• This is essential for the death of old enterocytes that shed into the lumen of intestinal
glands
b) It plays an important role in the cyclic sloughing of the inner layer of
endometrium, resulting in menstruation

3. An essential event during development and in adult stage:

a) A large number of neurons are produced during the development of CNS.
• But up to 50% of the neurons are removed by apoptosis during the formation of synapses
between neurons
b) Apoptosis is responsible for the removal of tissues of webs between
fingers and toes during developmental stage in fetus
c) It is necessary for regression and disappearance of duct systems during
sex differentiation in fetus

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 Activation of Apoptosis
• Apoptosis is activated by either:
1. Withdrawal of positive signals (survival factors) or
2. Arrival of negative signals

Withdrawal of positive signals

• Positive signals are the signals which are necessary
for the long-time survival of most of the cells.
• Positive signals are continuously produced by other
cells or some chemical stimulants.
• Examples of chemical stimulants are:
• Nerve growth factors (for neurons)
• Interleukin-2 (for cells like lymphocytes)

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 Activation of Apoptosis cont..
Arrival of negative signals
• Negative signals are the external or internal stimuli which
initiate apoptosis.

• Negative signals are produced during various events like:

• Normal developmental procedures
• Cellular stress
• Increase in the concentration of intracellular oxidants
• Viral infection
• Damage of DNA
• Exposure to agents like chemotherapeutic drugs, X-rays,
ultraviolet rays and the death-receptor ligands.
• Death receptor ligands are the substances which bind with specific cell
membrane receptors and initiate the process of apoptosis.
• Common death-receptor ligands are: tumor necrosis factors (TNF α, TNF β)
and Fas ligand (which binds to the receptor called Fas)

• Death receptors are the cell membrane receptors which receive the
death-receptor ligands.
• E.g. TNF receptor-1 (TNFR1) and TNF-related apoptosis inducing ligand
(TRAIL) receptors called DR4 and DR5

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 Abnormal Apoptosis
• Apoptosis within normal limits is beneficial for
the body.
• However, too much or too little apoptosis leads
to abnormal conditions.

• Common abnormalities due to too much

apoptosis:
• Ischemic related injuries
• Autoimmune diseases like:
• Hemolytic anemia- destruction on RBCs by ones immune
system
• Thrombocytopenia (low platelet counts)- Idiopathic
thrombocytopenic purpura (ITP)
• Acquired immunodeficiency syndrome (AIDS)
• Neurodegenerative diseases like Alzheimer’s disease.
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 Abnormal Apoptosis cont..
• Common abnormalities due to too little
apoptosis:
• Cancer
• Autoimmune lymphoproliferative syndrome
(ALPS)- inherited disorder whereby the body
cannot appropriately regulate the number of
lymphocytes.

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