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Cell & Molecular

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isaiabilafam526
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© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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CELL AND MOLECULAR BIOLOGY

Level 100, Bachelor of Technology

Felix Osei-Boakye
Ph.D Haematology & Transfusion Science (in-view),
MPhil. Haematology, BSc, & Dip. (Med. Lab. Science).
Sunyani Technical University
Department of Medical Laboratory Science
1
THE CELL

2
THE CELL

• All living things (or organisms) are built from cells:


- Cells are small membrane-enclosed units filled with a concentrated aqueous solution
of chemicals, and endowed with the extraordinary ability to create copies of
themselves by growing and then dividing in two

• Higher organisms, including ourselves, are communities of cells derived by


growth and division from a single founder cell

• Every animal or plant is a vast colony of individual cells, each of which performs a
specialized function that is integrated by intricate systems of cell-to-cell
communication

3
The Cell

• Also, cells differ vastly in shape/form, function, and chemical requirements


- Animal cells differ from those in a plant, and even cells within a single multicellular
organism can differ widely in appearance and activity

• Some require oxygen to live, whereas, for others the gas is deadly
- Some cells consume little/more carbon dioxide (CO2), sunlight, and water as their
raw materials
- Also, others need a complex mixture of molecules produced by other cells

• *

4
The Cell

• Despite the extraordinary diversity of plants and animal species, people have
recognized from time immemorial that these organisms have something in
common that entitles them to be called living organisms
- Sensitive or respond to the environment, capable of reproduction, growth and
development, regulation, homeostasis, and energy processing

• Another property of living cells is the presence of soluble enzymes located in the
cytoplasm
- Cellular enzymes catalyze biosynthesis of the low molecular weight precursors to
protein and nucleic acids

• Based on differences in compartmentalization, living cells may be divided into two


types, the simpler prokaryotic cell and the more complex eukaryotic cell

5
The Cell

6
Prokaryotic Cell

Prokaryotic cells have a cell wall, cytoplasmic membrane, soluble


cytoplasmic enzymes, and a nucleoid region that holds a single
chromosome
7
Prokaryotic Cell

• Prokaryotes include cells of two domains, the Archaea and the Bacteria, which
diverged early in evolution
- The Archaea include cells that live in extreme environments that are unusual today
but may have been prevalent in primitive Earth. For example, thermoacidophiles live
in hot sulfur springs with temperatures as high as 80°C and pH values as low as 2

• All prokaryote cell components are located together in the same compartment
- They are made of a single compartment

• Prokaryotic cells are smaller and simpler than most eukaryotic cells, their
genomes are less complex, and they do not contain nuclei

8
Prokaryotic Cell

• Most prokaryotic cells are spherical, rod-shaped, or spiral, with diameters of


1μm to 10μm

• Bacteria are the common forms of prokaryotes found in present-day – they


comprise a large group of organisms that live in a wide range of environments,
including soil, water, and other organisms (e.g., human pathogens)

• The largest and most complex prokaryotes are the Cyanobacteria - bacteria in
which photosynthesis evolved

9
Photograph of a primitive hot spring in East Africa
Hot springs are good sites to find archaea
10
Eukaryotic Cell

11
Eukaryotic Cell

• Like prokaryotic cells, all eukaryotic cells are surrounded by a plasma membrane
and contain ribosomes
• However, eukaryotic cells are much more complex and contain a nucleus and a
variety of cytoplasmic organelles

• The largest and most prominent organelle of eukaryotic cells is the nucleus, with
a diameter of approximately 5μm
• The nucleus contains the genetic information of the cell, which in eukaryotes is
organized as linear rather than circular DNA molecules

• The nucleus is the site of DNA replication and of RNA synthesis; the translation of
RNA into proteins takes place on ribosomes in the cytoplasm

12
Eukaryotic Cell

• In addition to a nucleus, eukaryotic cells contain a variety of membrane-enclosed


organelles within their cytoplasm. These organelles provide compartments in
which different metabolic activities are localized

• Eukaryotic cells are generally much larger than prokaryotic cells, frequently
having a cell volume at least a thousandfold greater

• The larger and more complicated cells of higher eukaryotic organisms (animals,
fungi, plants, and protists) are subdivided into separate compartments and are
called eukaryotic cells.

13
Features that Distinguish Eukaryotic and Prokaryotic Cells

Assignment 1

• Explain the differences between prokaryotic and eukaryotic cells

14
Cellular Organization

• Every human cell has a plasma membrane, a nucleus, and cytoplasm


- Some exceptions to this rule exist - A mature erythrocyte (red blood cell) eliminates its
nucleus once development is complete. Thus, erythrocytes are anucleate

- Cells of skeletal muscle, liver, and other tissues may have up to 50 nuclei and are
multinucleate

15
The Plasma Membrane
• Our cells are surrounded by an outer membrane (plasma membrane) that is formed
by phospholipid and protein
• The plasma membrane separates the inside of the cell (cytoplasm) from the
outside
- Therefore, it serves as an interface that allows the internal part of the cell to interact with
the external environment
• The membrane is physically weak and flexible. Most bacterial and plant cells have
hard cell walls, though animal cells usually do not
• The plasma membrane is a phospholipid bilayer with proteins either attached (also
called peripheral proteins) or embedded (also called integral proteins)

16
The Plasma Membrane

• The phospholipid molecule has a polar head and nonpolar tails


• Because the polar heads are charged, they are hydrophilic (water-loving) and
face outward, where they are likely to encounter a watery environment
• The nonpolar tails are hydrophobic (water-fearing) and face inward, where there
is no water
• At body temperature, the phospholipid bilayer is a liquid; it has the consistency
of olive oil, and the proteins are able to change their positions by moving
laterally
• A working description of membrane structure is called the fluid-mosaic model

17
Cellular Organization
The Plasma Membrane

18
The Plasma Membrane

• Also, the plasma membrane contains a substantial number of cholesterol


molecules

• These molecules stabilize the phospholipid bilayer and prevent a drastic


decrease in fluidity at low temperatures

• Short chains of sugars are attached to the outer surfaces of some protein and
lipid molecules (called glycoproteins and glycolipids, respectively)
- These carbohydrate chains, specific to each cell, mark the cell as belonging to a
particular individual
- Such cell markers account for such characteristics as blood type or why a patient’s
system sometimes rejects an organ transplant

• Some glycoproteins have a special configuration that allows them to act as a


receptor for a chemical messenger such as a hormone. Some integral plasma
membrane proteins
19
Cellular Organization

The Plasma Membrane

• Membrane-bounded compartments give eukaryotic cells a number of advantages


• The membranes provide a barrier that allows each type of organelle to maintain
ionic and enzymatic interior environments
• The plasma membrane is impermeable to ions and most water-soluble
molecules, due to the hydrophobic interior of its lipid bilayer
• The phospholipid layers are oriented with their hydrophobic tails inward and their
hydrophilic heads outward

20
Cellular Organization

The Nucleus

• The presence of a nucleus is the principal feature that distinguishes eukaryotic cells
from prokaryotic cells

• The nucleus is a prominent structure in human cells. The nucleus is of primary


importance because it stores the genetic information and serves as the cell’s
control center
- that determines the characteristics of the body’s cells and their metabolic function

• DNA replication, transcription, and RNA processing all take place within the
nucleus, whereas, the final stage of gene expression (translation) localized to the
cytoplasm

21
Cellular Organization

The Nucleus

• The unique chemical composition of each person’s DNA forms the basis for DNA
fingerprinting

• The nucleus is separated from the cytoplasm by a double membrane known as the
nuclear envelope, which is continuous with the endoplasmic reticulum

• The nuclear envelope has nuclear pores of sufficient size to permit the passage of
proteins into the nucleus and ribosomal subunits out of the nucleus
• Additionally, the double membrane of the nuclear envelope surrounds and contains
cellular DNA, protecting the vital genetic information contained within its molecules

22
Cellular Organization

Ribosomes
• Ribosomes are composed of two subunits, one large and one small. Each subunit
has its own mix of proteins and rRNA
• Protein synthesis occurs at the ribosomes

• Ribosomes are found free within the cytoplasm either singly or in groups called
polyribosomes (called polysomes for short)
• Ribosomes are often attached to the endoplasmic reticulum, a membranous
system of saccules and channels

• Proteins synthesized by cytoplasmic ribosomes are used inside the cell for various
purposes. Those produced by ribosomes attached to endoplasmic reticulum may
eventually be secreted from the cell
23
Cellular Organization

Endoplasmic Reticulum
• The endoplasmic reticulum (ER), a complicated system of membranous channels
and saccules (flattened vesicles), is physically continuous with the outer
membrane of the nuclear envelope. Rough ER is studded with ribosomes on the
side of the membrane that faces the cytoplasm
• Here proteins are synthesized and enter the ER interior where processing and
modification begin. Some of these proteins are incorporated into membrane, and
some are for export. Smooth ER, which is continuous with rough ER, does not have
attached ribosomes
• Smooth ER synthesizes the phospholipids that occur in membranes and has
various other functions, depending on the particular cell
- In the testes, it produces testosterone, and in the liver it helps detoxify drugs

24
Cellular Organization

Mitochondria
• Are bounded by a double membrane
• The inner membrane is folded to form little shelves called cristae, which project
into the matrix, an inner space filled with a gel-like fluid
• Mitochondria are the site of ATP (adenosine triphosphate) production involving
complex metabolic pathways
- ATP molecules are the common carriers of energy in cells
• *

25
Cellular Organization
Mitochondria
• The mitochondrion is often called the powerhouse of the cell
• Just as a powerhouse burns fuel to produce electricity, the mitochondria convert the
chemical energy of carbohydrate molecules into the chemical energy of ATP
molecules
• In the process, mitochondria use up oxygen and give off carbon dioxide and water

• The oxygen you breathe in enters cells and then mitochondria; the carbon dioxide
you breathe out is released by mitochondria
- Because oxygen is used up and carbon dioxide is released, we say that mitochondria
carry on cellular respiration
26
Cellular Organization

Mitochondria
• Fragments of digested carbohydrate, protein, and lipid enter the mitochondrial
matrix from the cytoplasm
• The matrix contains enzymes for metabolizing these fragments to carbon dioxide
and water
• Energy released from metabolism is used for ATP production, which occurs at the
cristae
- The protein complexes that aid in the conversion of energy are located in an assembly-
line fashion on these membranous shelves
• Many cells use ATP to carry out their specialized functions
- For example, muscle cells use ATP for muscle contraction, which produces movement,
and
- nerve cells use it for the conduction of nerve impulses, which make us aware of our
environment

27
Cellular Organization
The Cytoskeleton
• Several types of filamentous protein structures form a cytoskeleton, and this helps
to maintain the shape of the cell, and either anchors the organelles or assists
their movement as appropriate
• The cytoskeleton includes microtubules, intermediate filaments, and actin filaments

a. Microtubules are hollow cylinders whose wall is made up of 13 longitudinal rows


of the globular protein tubulin
• Microtubules can assemble and disassemble, an the assembly process is regulated
by the centrosome, which lies near the nucleus. The centrosome is the region of
the cell that contains the centrioles
• Microtubules radiate from the centrosome, helping to maintain the shape of the cell
and acting as tracks along which organelles move
• During cell division, microtubules form spindle fibers, which assist the movement of
chromosomes

28
Cellular Organization
The Cytoskeleton

b. Intermediate filaments differ in structure and function. Because they are tough
and resist stress, intermediate filaments often form cell-to-cell junctions
• Intermediate filaments join skin cells in the outermost skin layer, the epidermis

c. Actin filaments are long, and extremely thin fibers that usually occur in bundles
or groups
• Actin filaments have been isolated from various types of cells, especially those in
which movement occurs
• Microvilli, which project from certain cells and can shorten and extend, contain actin filaments.
Actin filaments, like microtubules, can assemble and disassemble

29
DISCUSSION

30
TRANSPORT ACROSS THE PLASMA MEMBRANE

• The plasma membrane keeps the content of a cell intact


• It is selectively permeable, and therefore, allows only certain molecules and ions
to enter and exit the cytoplasm freely
• Both passive and active transport methods are used to cross the plasma
membrane

31
Transport across the plasma membrane
Simple Diffusion
• Diffusion is the spontaneous movement of simple atoms or molecules from an
area of higher concentration to an area of lower concentration until they are
equally distributed
• Eventually eliminating the concentration difference between the two regions
- To illustrate diffusion, imagine putting a tablet of dye into water
- The water eventually takes on the color of the dye as the dye molecules diffuse

32
Transport across the plasma membrane

Simple Diffusion
• The chemical and physical properties of the plasma membrane allow only a few
types of molecules to enter and exit a cell by simple diffusion
- However, lipid-soluble molecules such as alcohols can diffuse through the membrane
because lipids are the membrane’s main structural components

• Gases can also diffuse through the lipid bilayer; this is the mechanism by which
oxygen enters cells and carbon dioxide exits cells
- For example, consider the movement of oxygen from the lungs to the bloodstream
- When you inhale, oxygen fills the tiny air sacs (alveoli) within your lungs. Neighboring
lung capillaries contain red blood cells with a very low oxygen concentration
- Oxygen diffuses from the area of higher (oxygen) concentration to the area of lower
(oxygen) concentration: first through alveolar cells, then lung capillary cells, and
finally into the red blood cells

33
Transport across the plasma membrane

Simple Diffusion
• When atoms or molecules diffuse from areas of higher to lower concentration
across plasma membranes, no cellular energy is involved
• Instead, kinetic or thermal energy of matter is the energy source for diffusion

34
Transport across the plasma membrane
Osmosis
• In osmosis, there is the movement of solvent molecules across a
semipermeable membrane, from a region of higher water concentration to a
region of lower water concentration

• Water molecules move more rapidly through the membrane of a cell than
dissolved ions or small polar organic solutes, which are considered
nonpenetrating
- Because of this difference in the penetrability of water versus solutes through the
plasma membrane, the membrane is said to be semipermeable

35
Transport across the plasma membrane

Osmosis
• Osmosis occurs whenever an unequal concentration of water exists on either
side of a selectively permeable membrane
- In a solution, water is more concentrated when it contains fewer dissolved
substances, or solutes, (and thus is closest to pure water)
- Water is less concentrated as solute concentration increases

• (Recall that a selectively permeable membrane allows water to pass freely, but
not most dissolved substances)

• Osmotic pressure is the force exerted on a selectively permeable membrane


when water moves from an area of higher water concentration (lower solute
concentration) to an area of lower water concentration (higher solute
concentration)

36
Transport across the plasma membrane

Osmosis

• When two compartments of different solute concentration are separated by a


semipermeable membrane, the compartment of higher solute concentration is
said to be hypertonic (or hyperosmotic),
• whereas, the compartment with lower solute concentration, which is described as
being hypotonic (or hypoosmotic)
• Once the internal solute concentration of a cell equals the external solute
concentration, the internal and external fluids are isotonic (or isosmotic), and
no net movement of water into or out of the cells occurs
• When a cell is placed into a hypotonic solution, the cell rapidly gains water by
osmosis and swells

37
Transport across the plasma membrane

Osmosis

• Conversely, a cell placed into a hypertonic solution rapidly loses water by


osmosis and shrinks
• By these simple observations, it is evident that the volume of a cell is
controlled by the difference between the solute concentration inside the cell
and that in the extracellular medium

38
Transport across the plasma membrane
Osmosis
(a) A cell placed in a
hypotonic solution (one
having a lower solute
concentration than the cell)
swells because of a net gain
of water by osmosis

(b) A cell in a hypertonic


solution shrinks because of a
net loss of water by osmosis

(c) A cell placed in an isotonic


solution maintains a constant E.g. Your digestive tract, for example, secretes several
volume because the inward liters of fluid daily, which is reabsorbed osmotically by
flux of water is equal to the the cells that line your intestine
outward flux
39
Transport by Carriers

Facilitated Transport
• Substances always diffuse across the plasma membrane, when the concentrations
of substances on either sides/regions of the membrane are different
• However, most solutes do not simply diffuse across a plasma membrane
- Also, they do not always diffuse through the lipid bilayer or through a channel
- Instead, they are transported by means of protein carriers within the membrane

• In facilitated transport (facilitated diffusion), solute molecules (e.g., an amino


acids or glucose) are transported across the plasma membrane from the side of
higher concentration to the side of lower concentration

• The cell does not require energy for this type of transport because the molecules
are moving down their concentration gradient

40
Transport by Carriers

Facilitated Transport

• Facilitated diffusion mediates the entry and exit of polar solutes, such as sugars
and amino acids, that do not penetrate the lipid bilayer

• Unlike ion channels, which can conduct millions of ions per second, most
facilitative transporters can move only hundreds to thousands of solute molecules
per second across the membrane

• The activity of facilitative transporters can be regulated, like enzymes and ion
channels

41
Transport by Carriers

Facilitated Transport
• In many cases, the diffusing substance
first binds selectively to a membrane-
spanning protein, called a facilitative
transporter, that facilitates the
transport/diffusion process

• Facilitated diffusion is similar in many


ways to an enzyme-catalyzed reaction.
Just like enzymes, facilitative
transporters are specific for the
molecules they transport, and are able
to discriminate between non-specific
solute molecules

42
Transport by Carriers

Active Transport
• This is an energy-driven process where membrane proteins transport molecules
or ions across a cell membrane from a region of lower concentration to a region of
higher concentration, against the concentration gradient

• Active transport requires a protein carrier and the use of cellular energy obtained
from the breakdown of ATP

• Proteins involved in active transport are often called pumps


- because just as a water pump uses energy to move water against the force of gravity,
proteins use energy to move substances against their concentration gradients

- There is one type of pump that is active in all cells but is especially associated with
nerve and muscle cells
- This pump moves sodium ions (Na+) to the outside of the cell and potassium ions (K+) to
the inside of the cell
*

43
Transport across the plasma membrane

Active Transport
• When ATP is broken down, energy is released, and in this case the energy is
used by a carrier to carry out active transport
• Therefore, cells involved in active transport have a large number of mitochondria
near the plasma membrane at which active transport is occurring

44
DISCUSSION

45
Transport across the plasma membrane

Endocytosis and Exocytosis


• The carrier and channel proteins discussed in the preceding slides transport
small molecules through the phospholipid bilayer

• Eukaryotic cells are also able to ingest large particles (such as bacteria) and
the uptake of fluids or macromolecules in small vesicles from the surrounding
medium by a distinct process called endocytosis

• During endocytosis, a portion of the plasma membrane forms an inner pocket


to engulf (envelop) a substance, and the membrane then buds off to form an
intracellular vesicle containing the ingested material

46
Transport across the plasma membrane

Endocytosis and Exocytosis


Two forms of endocytosis exist: (1) Phagocytosis and (2) Pinocytosis
• Phagocytosis (cell eating) occurs largely in specialized types of cells, whereas,
other forms of endocytosis take place in all eukaryotic cells
• Phagocytosis, or “cell eating,” is a mechanism whereby the cell can ingest solid
particles
- White blood cells consume bacterial cells by phagocytosis. Once inside the cell, the
bacterial cell can be destroyed
• Pinocytosis, or “cell drinking,” allows the cell to consume solutions
- An infant’s intestinal lining ingests breast milk by pinocytosis, allowing the mother’s
protective antibodies to enter the baby’s bloodstream

• During exocytosis, a vesicle fuses with the plasma membrane as secretion occurs

47
Transport across the plasma membrane

48
THE CELL CYCLE

Level 100, Bachelor of Technology

Felix Osei-Boakye
Ph.D Haematology & Transfusion Science (in-view),
MPhil. Haematology, BSc, & Dip. (Med. Lab. Science).
Sunyani Technical University
Department of Medical Laboratory Science
49
THE CELL CYCLE
• A cell reproduces by carrying out an orderly sequence of events in which it
duplicates its contents and then divides in two
• This sequence of events from the time a cell divides to the time the resulting daughter cells
also divide is called “the cell cycle”

• The cell cycle in higher eukaryotes is carefully regulated by internal and external
signals
- For example, growth factors are external signals received at the plasma membrane
that cause a resting cell to undergo the cell cycle
- When blood platelets release a growth factor, skin fibroblasts in the vicinity finish the
cell cycle, thereby repairing an injury

• Other signals ensure that the stages follow one another in the normal sequence
and that each stage is properly completed before the next stage begins

50
The Cell Cycle

To explain how cells reproduce, it is important that we are able to answer these 3
major questions

1. How do cells duplicate their contents - including the chromosomes, which carry
the genetic information?

2. How do they partition the duplicated contents and split in two?

3. How do they coordinate all the steps and machinery required for these two
processes?

51
The Cell Cycle

• When appropriate signals are present, a cell doubles its organelles and
accumulates materials needed for DNA synthesis and cell division

• During the cell cycle, there is replication of genetic materials, subsequent mitosis,
and specialization of cells due to existing needs. These processes allow humans to
grow and also repair damaged tissues

• Although, the cell cycle focuses on cell proliferation, many cells in “animals” remain
permanently in a state of quiescence (G0 phase),
- whereas others can resume proliferation if stimulated by appropriate growth factors or
other extracellular signals

52
The Cell Cycle
Types of Cells
Proliferative (Labile) cells - these type of cells are constantly going through the
cell cycle
Examples of proliferative cells include:
• Epithelium of skin, Gastrointestinal tract (GIT), Urinary tract, Haematopoietic stem
cells (in the red bone marrow)

53
The Cell Cycle
Types of Cells
Stable cells – cells that do not replicate/go through the cell cycle all the time. These
type of cells can initiate the cell cycle when they are stimulated by a strong signal

Examples of stable cells include:

• Liver cell (hepatocyte), Epithelium of kidney tubules, Alveolar cells of the lungs

Permanent cells (Amitotic) – once these types of cells have completed the cell cycle,
they do not go through it again

Example of permanent cells include:

• Neurons, Skeletal muscle, Cardiac muscle (myocardium)


54
The Cell Cycle
The cell cycle has 2 major phases

1. Interphase
− G1 Phase
− Synthesis Phase (S Phase)
− G2 Phase

2. Mitotic phase
− Mitosis
− Cytokinesis

• The passage of animal cells through the cell cycle is regulated primarily by the
extracellular growth factors that signal cell proliferation
• In the presence of the appropriate growth factors, a cell passes the restriction
checkpoint and enters the S phase 55
The Cell Cycle

• Once it has passed through the restriction point, the cell is committed to proceed
through the S phase and the rest of the cell cycle, even in the absence of further
growth factor stimulation
• However, if appropriate growth factors are not available in the G1, progression
through the cell cycle stops at the restriction checkpoint
• The arrested cell then enters a quiescent phase of the cell cycle called G0 phase,
where they can remain dormant for long periods of time without proliferating
56
INTERPHASE

• Two significant events occur during the interphase: these are replication of DNA
and protein synthesis

1. G1 Phase
• The cell doubles its organelles (mitochondria, ribosomes, etc) and accumulates
materials that will be used in DNA synthesis
- Some of which are proteins, including enzymes (like the replisomes)

• The proliferation of most animal cells is regulated in the G1 phase of the cell cycle

• A decision point in G1 Phase, called the restriction checkpoint in animal cells


determines the progression of the cell in the cycle

57
Interphase

− Cell cycle checkpoints

• The cell cycle has a number of restriction checkpoints:


places where the cell cycle stops if all is not well

• It is critically important that the cell do not begin mitosis


until replication of the genome has been completed

• The alternative would be a catastrophic cell division in


which the daughter cells fail to inherit complete copies of
the genetic material

58
Interphase
− Cell cycle checkpoints
• Progression through the cell cycle is stimulated by
extracellular signals, such as nutrients and growth
factors
• All events occurring in different stages of the cell cycle
must be coordinated with one another so that they occur
in the appropriate order

− For example, the checkpoint in G2 prevents the initiation


of mitosis if the cell contains DNA that has not been
completely replicated or contains unrepaired lesions

− The G1 checkpoint allows the repair of DNA damage


before the cell enters S phase, where the damaged DNA
would be replicated

− The S-phase checkpoint provides continual monitoring of


the integrity of DNA to ensure that damaged DNA is
repaired before it is replicated. Some of the errors include,
errors that occur during DNA replication, such as the
incorporation of incorrect bases or incomplete replication
of DNA segments
59
- Cell cycle checkpoints

Apoptosis
• Any cell that did not successfully complete mitosis and is abnormal undergoes
apoptosis at the restriction checkpoint

• Apoptosis is often defined as programmed cell death because the cell progresses
through a series of events that bring about its destruction
- The cell rounds up and loses contact with its neighbors
- The nucleus fragments and the plasma membrane develops blisters
- Finally, the cell fragments and its bits and pieces are engulfed by white blood cells
and/or neighboring cells

• Apoptosis is considered autonomous cellular


destruction that avoids the release of inflammatory
cellular content
• Necrosis, however, is passive and accidental cell death
resulting from environmental perturbations, and
associated with uncontrolled release of inflammatory
cellular contents
60
Interphase

2. Synthesis Phase (S Phase)


• DNA replication occurs here. At the beginning of this phase, each chromosome is
composed of one DNA double helix, which is equal to one chromatid
• At the end of this phase, each chromosome has two identical DNA double helix
molecules, and therefore is composed of two sister chromatids
− This means that, DNA replication has resulted in duplication of chromosomes

3. G2 Phase
• This phase is primarily focused on cell growth. For example, the cytoplasm of the
cell increases in size in order to make provision for cell division
• The cell synthesizes proteins that will assist cell division, such as the proteins
found in microtubules

61
Summary

62
Discussion

63
MITOTIC PHASE

• After the interphase, the cell enters the M phase where cell division occurs
• There is division of the nucleus (Mitosis) and division of the cytoplasm
(Cytokinesis)
• During mitosis, chromosomes are distributed to two separate nuclei. When
cytokinesis is complete, two daughter cells are present

• Mitosis begins with doubling of centrioles. Then, each chromosome is duplicated


- it is composed of two chromatids held together at a central region, called the
centromere
• Mitosis is subdivided into four phases: prophase, metaphase, anaphase, and
telophase

64
Mitotic Phase
Prophase
• Four major activities occur at this phase that indicate the cell is about to divide
• The two pairs of centrioles outside the nucleus begin moving away from each other
toward opposite ends of the nucleus
• Spindle fibers appear between the separating centriole pairs
• The nuclear envelope begins to fragment, and the nucleolus begins to disappear
• Condensation of the chromatin to sister chromatids

65
Metaphase
• The nuclear envelope is fragmented, and the spindle occupies the region formerly
occupied by the nucleus
• Spindle fibers attach to the centromeres as the chromosomes continue to shorten
and thicken
• The paired chromosomes are now at the equator (center) of the spindle. Metaphase
is characterized by a fully formed spindle, and each chromosome with two sister
chromatids, are aligned at the equator

66
Mitotic Phase
Anaphase
• The sister chromatids separate from each other. Once the chromatids are separated,
they are called chromosomes
• Separation of the sister chromatids ensures that each cell receives a copy of each
type of chromosome and a full complement of genes
• During anaphase, the daughter chromosomes move to the poles of the spindle
• Anaphase is characterized by the movement of chromosomes toward each pole and
thus, to opposite sides of the cell

67
Mitotic Phase
Telophase
• Telophase begins when the chromosomes arrive at the poles. During telophase, the
chromosomes become indistinct chromatin again
• The spindle disappears as nucleoli appear, and nuclear envelope components
reassemble in each cell. Telophase is characterized by the presence of two daughter
nuclei

68
Mitotic Phase
Cytokinesis
• Cytokinesis is division of the cytoplasm and organelles
• In human cells, a slight indentation called a cleavage furrow passes around the
circumference of the cell. Actin filaments form a contractile ring, and as the ring gets
smaller and smaller, the cleavage furrow pinches the cell in half. As a result each cell
becomes enclosed by its own plasma membrane

69
Summary of Mitosis

70
BIOLOGICAL RELEVANCE OF THE CELL CYCLE
Tissue repair/ tissue replacement

• Skin fibroblasts are arrested in G0 phase until they are stimulated to divide
- This becomes necessary when repair of damaged tissue resulting from a wound is
required

• When there is an injury to the skin, platelets respond to initiate haemostasis by


forming a platelet plugs, and further activates clotting factors through a cascade to
form fibrin clots that eventually stop the bleeding

• This triggers the release of platelet-derived growth factor (PDGF) from blood
platelets during the clotting process
- This signal induces fibroblasts in the vicinity of the damaged tissue undergo the cell cycle
and proliferate in order to repair the damaged tissue
71
Biological relevance of the cell cycle
Conception and foetal development

• When appropriate signals are present, a cell doubles its organelles and accumulates
materials needed for DNA synthesis and cell division
- During the cell cycle, there is replication of genetic materials, and subsequent
mitosis

• These processes allow humans to grow by ensuring that a cell duplicates to produce
daughter cells of the same kind, and with the same number of diploid chromosomes
- During fertilization, a foetus inherits its genome from both parent gamete cells
(haploid cells) in order to possess a complete human genome, which typically
has 46 chromosomes: 23 each from maternal- and paternal sources

• As the foetus develops, mitotic division of the cells occurs in the mother’s uterus to
produce identical cells, and this enable the formation of tissues, organs/organ systems, and
the overall growth and development of the foetus

72
Monosomy 9
Several genes that control cell growth
and division are found on Chromosome 9

Most of these genes are tumor


suppressors

73
Trisomy 21
Causes Down Syndrome
Characterised by developmental and intellectual delay

74
Discussion

75
DNA REPLICATION

76
DNA REPLICATION

• The ability of a cell to survive and proliferate in a chaotic environment


depends on the accurate duplication of the vast quantity of genetic
information carried in its DNA
- This duplication process, is called DNA replication,
- and must occur before a cell can divide to produce two genetically identical
daughter cells

• The fundamental biological process of reproduction requires the faithful


transmission of genetic information from parent to offspring

• Maintaining order in a cell also requires the continual surveillance and repair
of its genetic information through a process called proofreading

77
DNA Replication

• Although a proofreading mechanism exists for protecting a cell’s DNA from


copying errors and accidental damage, permanent changes or mutations in
DNA sometimes occur, through:
- Exposure to some chemicals and radiation in the environment and also, by
reactive molecules that are generated inside the cell

• Therefore, accurate replication of genomic DNA is essential to the lives of all


cells and organisms
• Each time a cell divides, its entire genome must be duplicated, and complex
enzymatic machinery is required to copy the large DNA molecules that make up
the chromosomes
• This enzymatic machinery catalyzes some of the most rapid and accurate
processes that take place within cells

78
DNA Replication
• Deoxyribonucleic acid (DNA) stores genetic
information

• Making use of the information requires RNA


and protein

• Messenger RNA (mRNA) carries the


information for making proteins from the
genes to the cytoplasm

• The DNA double helix must be opened up for


RNA polymerase to read the template strand
and make RNA

79
DNA Replication
Central Dogma of Molecular Biology
• In all living cells, genetic information flows
from DNA to RNA (transcription) and from
RNA to protein (translation) – an
arrangement known as the central dogma

• The sequence of nucleotides in a


particular segment of DNA (a gene) is
transcribed into an RNA molecule, which
can then be translated into the linear
sequence of amino acids of a protein

- Only a small part of the gene, RNA, and protein is


shown
80
DNA Replication
Structure of the DNA

• A molecule of DNA consists of two long


polynucleotide chains/strands

• Each chain, or strand, is composed of


four types of nucleotide subunits,
- and the two polypeptide strands are held
together by hydrogen bonds between the
base portions of the nucleotides

• The nucleotides are covalently linked


together in a chain through the sugars
and phosphates, which form a backbone
- This is called phosphodiester bond

81
DNA Replication

82
DNA Replication
Structure of the DNA
• The nucleotides are composed of a nitrogen-containing base and a five-carbon
sugar, to which a phosphate group is attached

• For the nucleotides in DNA, the sugar is deoxyribose (hence the name
deoxyribonucleic acid) and the base can be either adenine (A), cytosine (C),
guanine (G), and thymine (T)

83
DNA Replication
• DNA replication occurs in the Synthesis phase (S phase) of the cell cycle. Here, an
exact copy of the DNA helix is produced. This happens with the assistance of
replication enzyme complex called replisomes

• The double-stranded structure of the DNA makes replication possible because


each old (parental) DNA strand serves as a template for each new (daughter)
strand

84
DNA Replication

• The two strands that make up the parental DNA are bonded to each other by
hydrogen bonds, which can be seen as either a

- Double bond between A and T, whereas a triple bond between C and G

85
DNA Replication
1. During replication, the old (parental) DNA strands unwind and unzip (i.e., the weak
hydrogen bonds between the two strands break). These two processes are
catalyzed by the enzyme, helicase

• The unzipping of the DNA double strands creates a replication fork

86
DNA Replication
2. New complementary nucleotides, which are always present in the nucleus, pair
with the nucleotides in the old strands

- The enzyme DNA polymerase III adds new nucleotides forming new (daughter)
complementary strands. A pairs with T, and C pairs with G
- Also, DNA polymerase proofreads its own work. If an incorrect nucleotide is
accidentally added to a growing strand, the DNA polymerase cleaves it from the strand
and replaces it with the correct nucleotide before continuing

87
DNA Replication

88
DNA Replication
Replication fork

89
DNA REPLICATION ENZYMES/PROTEINS
• Helicase – Helicase binds to the DNA and allows the unwinding/untwisting of
the DNA helix structure. Also, it breaks the hydrogen bonds holding the two
parent DNA strands together to provide two template strands for the synthesis
of new DNA

• Topoisomerase – Prevents tangling and knotting of DNA as the strands are


unzipped

• DNA Polymerase – Is responsible for DNA replication, by adding/pairing


nucleotides to each side of the template strands in the 5′ to 3′ direction to
produce new strands complementary to the parent strand
- Also, DNA Polymerase proofreads its work and corrects nucleotide mismatch
- Is responsible for changing the RNA primers into DNA (changing the base Uracil to into
Thymidine)

90
DNA Replication Enzymes/Proteins

• RNA Primase – Synthesizes short RNA sequences (primers) that are


complementary to a single-strand DNA template

• Ligase – This enzyme joins the Okazaki fragments forming the growing lagging
strand
• Gyrase – Gyrase returns the DNA strands into a double helix, and also, zips the
DNA back together

• Telomerase – Each time a cell divides, the telomeres lose a small amount of
DNA and become shorter. Telomerase adds DNA to the telomeres and prevents
the cells from damage and death

91
PROPOSED DNA REPLICATION MODELS

1. Semiconservative replication model

2. Conservative replication model

3. Dispersive replication model

92
Proposed DNA Replication Models

The Semiconservative Model


• This model proposes that DNA strands
separate, and a complementary strand is
synthesized for each, so that daughter
chromatids have one old and one new
strand

Summary: one old, and one new strands

93
Proposed DNA Replication Models

The Conservative Model


• This model proposed that both strands of
one copy would be entirely old DNA, while
the other copy would have both strands of
new DNA

94
Proposed DNA Replication Models

The Dispersive Model


• This model proposes that dsDNA might
fragment, replicate DNA, and then
reassemble, creating a mosaic of old and
new dsDNA regions in each new
chromosome

Summary: mosaic

95
Proposed DNA Replication Models

96
DISCUSSION

97
THE CELL CYCLE
• A cell reproduces by carrying out an orderly sequence of events in which it
duplicates its contents and then divides in two
• This sequence of events from the time a cell divides to the time the resulting daughter cells also
divide is called “the cell cycle”

• The cell cycle in higher eukaryotes is carefully regulated by internal and external
signals
- For example, growth factors are external signals received at the plasma membrane
that cause a resting cell to undergo the cell cycle
- When blood platelets release a growth factor, skin fibroblasts in the vicinity finish the
cell cycle, thereby repairing an injury

• Other signals ensure that the stages follow one another in the normal sequence
and that each stage is properly completed before the next stage begins

3
The Cell Cycle

To explain how cells reproduce, it is important that we are able to answer these 3 major
questions

1. How do cells duplicate their contents - including the chromosomes, which carry the
genetic information?

2. How do they partition the duplicated contents and split in two?

3. How do they coordinate all the steps and machinery required for these two processes?

4
The Cell Cycle

• When appropriate signals are present, a cell doubles its organelles and accumulates
materials needed for DNA synthesis and cell division
• During the cell cycle, there is replication of genetic materials, subsequent mitosis, and
specialization of cells due to existing needs. These processes allow humans to grow
and also repair damaged tissues
• Although, the cell cycle focuses on cell proliferation, many cells in “animals” remain
permanently in a state of quiescence (G0 phase),
- whereas others can resume proliferation if stimulated by appropriate growth factors or
other extracellular signals

5
The Cell Cycle
Proliferative (Labile) cells - these type of cells are constantly going through the cell
cycle. Examples of such cells include:
• Epithelium of skin, Gastrointestinal tract (GIT), Urinary tract, Haematopoietic stem
cells (in the red bone marrow)
Stable cells – cells that do not replicate/through the cell cycle all the time. These type
of cells can initiate the cell cycle when they are stimulated by a strong signal. Examples
of cells include:
• Liver cell (hepatocyte), Epithelium of kidney tubules, Alveolar cells of the lungs

Permanent cells (Amitotic) – once these types of cells have completed the cell cycle,
they do not go through it again. Example of cell include:
• Neurons, Skeletal muscle, Cardiac muscle (myocardium)

6
The Cell Cycle
The cell cycle has 2 major phases

• Interphase
− G1 Phase
− Synthesis Phase (S Phase)
− G2 Phase

• Mitotic phase
− Mitosis
− Cytokinesis

• The passage of animal cells through the cell cycle is regulated primarily by the
extracellular growth factors that signal cell proliferation
• In the presence of the appropriate growth factors, a cell passes the restriction
checkpoint and enters the S phase
7
The Cell Cycle

• Once it has passed through the restriction point, the cell is committed to proceed
through S phase and the rest of the cell cycle, even in the absence of further growth
factor stimulation
• However, if appropriate growth factors are not available in G , progression through the
cell cycle stops at the restriction point
1

• The arrested cell then enters a quiescent phase of the cell cycle called G where they
can remain dormant for long periods of time without proliferating
0

8
INTERPHASE
• Two significant events occur during the interphase: these are replication of DNA and
protein synthesis
1. G1 Phase
• The cell doubles its organelles (mitochondria, ribosomes, etc) and accumulates
materials that will be used in DNA synthesis
• Some of which are proteins, including enzymes (like the replisomes)

• The proliferation of most animal cells is regulated in the G1 phase of the cell cycle

• A decision point in G1, called the restriction checkpoint in animal cells determines the
progression of the cell in the cycle

9
Interphase

− Cell cycle checkpoints


• The cell cycle has a number of restriction checkpoints:
places where the cell cycle stops if all is not well

• It is critically important that the cell do not begin mitosis until


replication of the genome has been completed

• The alternative would be a catastrophic cell division in which


the daughter cells failed to inherit complete copies of the
genetic material

10
Interphase
− Cell cycle checkpoints
• Progression through the cell cycle is stimulated by
extracellular signals, such as nutrients and growth
factors
• All events occurring in different stages of the cell
cycle must be coordinated with one another so that
they occur in the appropriate order

− For example, the checkpoint in G2 prevents the


initiation of mitosis if the cell contains DNA that has
n o t be e n c o mple t e ly re plic a t e d o r c o n t a in s
unrepaired lesions
− The G1 checkpoint allows repair of any DNA damage
to take place before the cell enters S phase, where
the damaged DNA would be replicated
− T h e S - ph a se c h e c k po in t pro v ide s c o n t in u a l
monitoring of the integrity of DNA to ensure that
damaged DNA is repaired before it is replicated.
Some of the errors include, errors that occur during
DN A replic atio n, suc h as the inc o rpo ratio n o f 11
incorrect bases or incomplete replication of DNA
segments
- Cell cycle checkpoints

Apoptosis
• Any cell that did not successfully complete mitosis and is abnormal undergoes
apoptosis at the restriction checkpoint

• Apoptosis is often defined as programmed cell death because the cell progresses
through a series of events that bring about its destruction
• The cell rounds up and loses contact with its neighbors
• The nucleus fragments and the plasma membrane develops blisters
• Finally, the cell fragments and its bits and pieces are engulfed by white blood cells
and/or neighboring cells

12
Interphase

2. Synthesis Phase (S Phase)


• DNA replication occurs here. At the beginning of this phase, each chromosome is
composed of one DNA double helix, which is equal to one chromatid
• At the end of this phase, each chromosome has two identical DNA double helix
molecules, and therefore is composed of two sister chromatids
− This means that, DNA replication has resulted in duplication of chromosomes

3. G2 Phase
• This phase is primarily focused on cell growth. For example, the cytoplasm of the
cell increases in size in order to make provision for cell division
• The cell synthesizes proteins that will assist cell division, such as the proteins
found in microtubules

13
MITOTIC PHASE

• After the interphase, the cell enters the M phase where cell division occurs
• There is division of the nucleus (Mitosis) and division of the cytoplasm
(Cytokinesis)
• During mitosis, chromosomes are distributed to two separate nuclei. When
cytokinesis is complete, two daughter cells are present

• Mitosis begins with doubling of centrioles. Then, each chromosome is duplicated


- it is composed of two chromatids held together at a central region, called the
centromere
• Mitosis is subdivided into four phases: prophase, metaphase, anaphase, and
telophase

15
Mitotic Phase
Prophase
• Four major activities occur at this phase that indicate the cell is about to divide
• The two pairs of centrioles outside the nucleus begin moving away from each other
toward opposite ends of the nucleus
• Spindle fibers appear between the separating centriole pairs
• The nuclear envelope begins to fragment, and the nucleolus begins to disappear
• Condensation of the chromatin to sister chromatids

16
Metaphase
• The nuclear envelope is fragmented, and the spindle occupies the region formerly
occupied by the nucleus
• Spindle fibers attach to the centromeres as the chromosomes continue to shorten and
thicken
• The paired chromosomes are now at the equator (center) of the spindle. Metaphase is
characterized by a fully formed spindle, and each chromosome with two sister
chromatids, are aligned at the equator

17
Mitotic Phase
Anaphase
• The sister chromatids separate from each other. Once the chromatids are separated,
they are called chromosomes
• Separation of the sister chromatids ensures that each cell receives a copy of each
type of chromosome and a full complement of genes
• During anaphase, the daughter chromosomes move to the poles of the spindle
• Anaphase is characterized by the movement of chromosomes toward each pole and
thus, to opposite sides of the cell

18
Mitotic Phase
Telophase
• Telophase begins when the chromosomes arrive at the poles. During telophase, the
chromosomes become indistinct chromatin again. The spindle disappears as nucleoli
appear, and nuclear envelope components reassemble in each cell. Telophase is
characterized by the presence of two daughter nuclei
• Cytokinesis is division of the cytoplasm and organelles. In human cells, a slight
indentation called a cleavage furrow passes around the circumference of the cell.
Actin filaments form a contractile ring, and as the ring gets smaller and smaller, the
cleavage furrow pinches the cell in half. As a result each cell becomes enclosed by its
own plasma membrane

19
20
Summary of Mitosis

21
22
BIOLOGICAL RELEVANCE OF THE CELL CYCLE
Tissue repair/ tissue replacement

• Skin fibroblasts are arrested in G0 phase until they are stimulated to divide
- This becomes necessary when repair of damaged tissue resulting from a wound is
required

• When there is an injury to the skin, platelets respond to initiate haemostasis by


forming a platelet plugs, and further activates clotting factors through a cascade to
form fibrin clots that eventually stop the bleeding
• This triggers the release of platelet-derived growth factor (PDGF) from blood platelets
during the clotting process
- This signal induces f ibroblasts in the vicinity of the damaged tissue undergo the cell
cycle and proliferate in order to repair the damaged tissue

23
Biological relevance of the cell cycle
Conception and foetal development
• When appropriate signals are present, a cell doubles its organelles and accumulates
materials needed for DNA synthesis and cell division
- During the cell cycle, there is replication of genetic materials, and subsequent
mitosis
• These processes allow humans to grow by ensuring that a cell duplicates to produce
daughter cells of the same kind, and with the same number of diploid chromosomes
- During fertilization, a foetus inherits its genome from both parent gamete cells
(haploid cells) in order to possess a complete human genome, which typically has
46 chromosomes: 23 each from maternal- and paternal sources
• As the foetus develops, mitotic division of the cells occurs in the mother’s uterus to
produce identical cells, and this enable the formation of tissues, organs/organ
systems, and the overall growth and development of the foetus
25
Monosomy 9
Several genes that control cell growth
and division are found on Chromosome 9

Most of these genes are tumor


suppressors

26
Trisomy 21
Causes Down Syndrome
Characterised by developmental and intellectual delay

27
DNA REPLICATION
• Deoxyribonucleic acid (DNA) stores genetic
information

• Making use of the information requires RNA


and protein

• Me sse nge r R N A ( mR N A) c arrie s the


information for making proteins from the
genes to the cytoplasm

• The DNA double helix must be opened up for


RNA polymerase to read the template strand
and make RNA

30
DNA Replication

Central Dogma of Molecular Biology

• In all living cells, genetic information f lows


from DNA to RNA (transcription) and from
R N A t o p r o t e i n ( t ra n s l a t i o n ) – a n
arrangement known as the central dogma

• The se q ue nc e o f nuc le o tide s in a


particular segment of DNA (a gene) is
transcribed into an RNA molecule, which
can then be translated into the linear
sequence of amino acids of a protein

• Only a small part of the gene, RNA, and


protein is shown

31
DNA Replication
Structure of the DNA

• A molecule of DNA consists of two long


polynucleotide chains/strands

• Each chain, or strand, is composed of


four types of nucleotide subunits,
• and the two polypeptide strands are held
together by hydrogen bonds between the
base portions of the nucleotides

• The nucleotides are covalently linked


together in a chain through the sugars
and phosphates, which form a backbone

32
33
DNA Replication
• Structure of the DNA
• The nucleotides are composed of a nitrogen-containing base and a f ive-carbon
sugar, to which a phosphate group is attached

• Fo r the nuc leo tides in DN A, the sugar is deoxyribo se ( henc e the name
deoxyribonucleic acid) and the base can be either adenine (A), cytosine (C),
guanine (G), or thymine (T)

34
DNA Replication
• DNA replication occurs in the Synthesis phase (S phase) of the cell cycle. Here, an
exact copy of the DNA helix is produced. This happens with the assistance of
replication enzyme complex called replisomes

• The double-stranded structure of the DNA makes replication possible because each
old (parental) DNA strand serves as a template for each new (daughter) strand

• Before replication begins, the two strands that make up the parental DNA are
bonded to each other by hydrogen bonds, which can be seen as either a
- Double bond between A and T, whereas a triple bond between C and G

35
DNA Replication
1. During replication, the old (parental) DNA strands unwind and unzip (i.e., the weak
hydrogen bonds between the two strands break). These two processes are
catalyzed by the enzyme, helicase

• The unzipping of the DNA double strands creates a replication fork

36
DNA Replication
2. New complementary nucleotides, which are always present in the nucleus, pair
with the nucleotides in the old strands
• The enzyme DNA polymerase III adds new nucleotides forming new (daughter)
complementary strands. A pairs with T, and C pairs with G
• Also, DNA polymerase proofreads its own work. If an incorrect nucleotide is
accidentally added to a growing strand, the DNA polymerase cleaves it from the strand
and replaces it with the correct nucleotide before continuing

37
DNA Replication

38
DNA Replication
Replication fork

39
DNA REPLICATION ENZYMES/PROTEINS
• Helicase – Helicase binds to the DNA and allows the unwinding/untwisting of
the DNA helix structure. Also, it breaks the hydrogen bonds holding the two
parent DNA strands together to provide two template strands for the
synthesis of new DNA
• Topoisomerase – Prevents tangling and knotting of DNA as the strands are
unzipped
• DNA Polymerase – Is responsible for DNA replication, by adding/pairing
nucleotides to each side of the template strands in the 5′ to 3′ direction to
produce new strands complementary to the parent strand
• Also, DNA Polymerase proofreads its work and corrects nucleotide mismatch
• Is responsible for changing the RNA primers into DNA (changing the base Uracil to into
Thymidine)

40
DNA Replication Enzymes/Proteins

• RNA Primase – Synthesizes shor t RNA sequences (primers) that are


complementary to a single-strand DNA template
• Ligase – This enzyme joins the Okazaki fragments forming the growing
lagging strand
• Gyrase – Gyrase returns the DNA strands into a double helix, and also, zips
the DNA back together

• Telomerase – Each time a cell divides, the telomeres lose a small amount of
DNA and become shorter. Telomerase adds DNA to the telomeres and
prevents the cells from damage and death

41
PROPOSED DNA REPLICATION MODELS

1. Semiconservative replication

2. Conservative replication model

3. Dispersive replication model

42
Proposed DNA Replication Models

The Semiconservative Model


• This model proposes that DNA strands
separate, and a complementary strand is
synthesized for each, so that daughter
chromatids have one old and one new
strand

Summary: one old, and one new strands

43
Proposed DNA Replication Models

The Conservative Model


• This model proposed that both strands of
one copy would be entirely old DNA, while
the other copy would have both strands of
new DNA

44
Proposed DNA Replication Models

The Dispersive Model


• This model proposes that dsDNA might
fragment, replicate DNA, a nd t hen
reassemble , creating a mosaic of old and
new dsDNA regions in each new
chromosome

Summary: mosaic

45
Proposed DNA Replication Models

46
CELL AND MOLECULAR BIOLOGY
Level 100, Bachelor of Technology

Felix Osei-Boakye
Ph.D Haematology & Transfusion Science (in-view),
MPhil. Haematology, BSc, & Dip. (Med. Lab. Science).
Sunyani Technical University
Department of Medical Laboratory Science
1
THE CELL

2
THE CELL

• All living things (or organisms) are built from cells:


- Cells are small membrane-enclosed units filled with a concentrated aqueous solution
of chemicals, and endowed with the extraordinary ability to create copies of
themselves by growing and then dividing in two

• Higher organisms, including ourselves, are communities of cells derived by


growth and division from a single founder cell

• Every animal or plant is a vast colony of individual cells, each of which performs a
specialized function that is integrated by intricate systems of cell-to-cell
communication

3
The Cell

• Also, cells differ vastly in shape/form, function, and chemical requirements


- Animal cells differ from those in a plant, and even cells within a single multicellular
organism can differ widely in appearance and activity

• Some require oxygen to live, whereas, for others the gas is deadly
- Some cells consume little/more carbon dioxide (CO2), sunlight, and water as their
raw materials
- Also, others need a complex mixture of molecules produced by other cells

• *

4
The Cell

• Despite the extraordinary diversity of plants and animal species, people have
recognized from time immemorial that these organisms have something in
common that entitles them to be called living organisms
- Sensitive or respond to the environment, capable of reproduction, growth and
development, regulation, homeostasis, and energy processing

• Another property of living cells is the presence of soluble enzymes located in the
cytoplasm
- Cellular enzymes catalyze biosynthesis of the low molecular weight precursors to
protein and nucleic acids

• Based on differences in compartmentalization, living cells may be divided into two


types, the simpler prokaryotic cell and the more complex eukaryotic cell

5
The Cell

6
Prokaryotic Cell

Prokaryotic cells have a cell wall, cytoplasmic membrane, soluble


cytoplasmic enzymes, and a nucleoid region that holds a single
chromosome
7
Prokaryotic Cell

• Prokaryotes include cells of two domains, the Archaea and the Bacteria, which
diverged early in evolution
- The Archaea include cells that live in extreme environments that are unusual today
but may have been prevalent in primitive Earth. For example, thermoacidophiles live
in hot sulfur springs with temperatures as high as 80°C and pH values as low as 2

• All prokaryote cell components are located together in the same compartment
- They are made of a single compartment

• Prokaryotic cells are smaller and simpler than most eukaryotic cells, their
genomes are less complex, and they do not contain nuclei

8
Prokaryotic Cell

• Most prokaryotic cells are spherical, rod-shaped, or spiral, with diameters of


1μm to 10μm

• Bacteria are the common forms of prokaryotes found in present-day – they


comprise a large group of organisms that live in a wide range of environments,
including soil, water, and other organisms (e.g., human pathogens)

• The largest and most complex prokaryotes are the Cyanobacteria - bacteria in
which photosynthesis evolved

9
Photograph of a primitive hot spring in East Africa
Hot springs are good sites to find archaea
10
Eukaryotic Cell

11
Eukaryotic Cell

• Like prokaryotic cells, all eukaryotic cells are surrounded by a plasma membrane
and contain ribosomes
• However, eukaryotic cells are much more complex and contain a nucleus and a
variety of cytoplasmic organelles

• The largest and most prominent organelle of eukaryotic cells is the nucleus, with
a diameter of approximately 5μm
• The nucleus contains the genetic information of the cell, which in eukaryotes is
organized as linear rather than circular DNA molecules

• The nucleus is the site of DNA replication and of RNA synthesis; the translation of
RNA into proteins takes place on ribosomes in the cytoplasm

12
Eukaryotic Cell

• In addition to a nucleus, eukaryotic cells contain a variety of membrane-enclosed


organelles within their cytoplasm. These organelles provide compartments in
which different metabolic activities are localized

• Eukaryotic cells are generally much larger than prokaryotic cells, frequently
having a cell volume at least a thousandfold greater

• The larger and more complicated cells of higher eukaryotic organisms (animals,
fungi, plants, and protists) are subdivided into separate compartments and are
called eukaryotic cells.

13
Features that Distinguish Eukaryotic and Prokaryotic Cells

Assignment 1

Explain the differences between prokaryotic and eukaryotic cells

14
Cellular Organization

• Every human cell has a plasma membrane, a nucleus, and cytoplasm


- Some exceptions to this rule exist - A mature erythrocyte (red blood cell) eliminates its
nucleus once development is complete. Thus, erythrocytes are anucleate

- Cells of skeletal muscle, liver, and other tissues may have up to 50 nuclei and are
multinucleate

15
The Plasma Membrane
• Our cells are surrounded by an outer membrane (plasma membrane) that is formed
by phospholipid and protein
• The plasma membrane separates the inside of the cell (cytoplasm) from the
outside
- Therefore, it serves as an interface that allows the internal part of the cell to interact with
the external environment
• The membrane is physically weak and flexible. Most bacterial and plant cells have
hard cell walls, though animal cells usually do not
• The plasma membrane is a phospholipid bilayer with proteins either attached (also
called peripheral proteins) or embedded (also called integral proteins)

16
The Plasma Membrane

• The phospholipid molecule has a polar head and nonpolar tails


• Because the polar heads are charged, they are hydrophilic (water-loving) and
face outward, where they are likely to encounter a watery environment
• The nonpolar tails are hydrophobic (water-fearing) and face inward, where there
is no water
• At body temperature, the phospholipid bilayer is a liquid; it has the consistency
of olive oil, and the proteins are able to change their positions by moving
laterally
• A working description of membrane structure is called the fluid-mosaic model

17
Cellular Organization
The Plasma Membrane

18
The Plasma Membrane

• Also, the plasma membrane contains a substantial number of cholesterol


molecules

• These molecules stabilize the phospholipid bilayer and prevent a drastic


decrease in fluidity at low temperatures

• Short chains of sugars are attached to the outer surfaces of some protein and
lipid molecules (called glycoproteins and glycolipids, respectively)
- These carbohydrate chains, specific to each cell, mark the cell as belonging to a
particular individual
- Such cell markers account for such characteristics as blood type or why a patient’s
system sometimes rejects an organ transplant

• Some glycoproteins have a special configuration that allows them to act as a


receptor for a chemical messenger such as a hormone. Some integral plasma
membrane proteins
19
Cellular Organization

The Plasma Membrane

• Membrane-bounded compartments give eukaryotic cells a number of advantages


• The membranes provide a barrier that allows each type of organelle to maintain
ionic and enzymatic interior environments
• The plasma membrane is impermeable to ions and most water-soluble
molecules, due to the hydrophobic interior of its lipid bilayer
• The phospholipid layers are oriented with their hydrophobic tails inward and their
hydrophilic heads outward

20
Cellular Organization

The Nucleus

• The presence of a nucleus is the principal feature that distinguishes eukaryotic cells
from prokaryotic cells

• The nucleus is a prominent structure in human cells. The nucleus is of primary


importance because it stores the genetic information and serves as the cell’s
control center
- that determines the characteristics of the body’s cells and their metabolic function

• DNA replication, transcription, and RNA processing all take place within the
nucleus, whereas, the final stage of gene expression (translation) localized to the
cytoplasm

21
Cellular Organization

The Nucleus

• The unique chemical composition of each person’s DNA forms the basis for DNA
fingerprinting

• The nucleus is separated from the cytoplasm by a double membrane known as the
nuclear envelope, which is continuous with the endoplasmic reticulum

• The nuclear envelope has nuclear pores of sufficient size to permit the passage of
proteins into the nucleus and ribosomal subunits out of the nucleus
• Additionally, the double membrane of the nuclear envelope surrounds and contains
cellular DNA, protecting the vital genetic information contained within its molecules

22
Cellular Organization

Ribosomes
• Ribosomes are composed of two subunits, one large and one small. Each subunit
has its own mix of proteins and rRNA
• Protein synthesis occurs at the ribosomes

• Ribosomes are found free within the cytoplasm either singly or in groups called
polyribosomes (called polysomes for short)
• Ribosomes are often attached to the endoplasmic reticulum, a membranous
system of saccules and channels

• Proteins synthesized by cytoplasmic ribosomes are used inside the cell for various
purposes. Those produced by ribosomes attached to endoplasmic reticulum may
eventually be secreted from the cell
23
Cellular Organization

Endoplasmic Reticulum
• The endoplasmic reticulum (ER), a complicated system of membranous channels
and saccules (flattened vesicles), is physically continuous with the outer
membrane of the nuclear envelope. Rough ER is studded with ribosomes on the
side of the membrane that faces the cytoplasm
• Here proteins are synthesized and enter the ER interior where processing and
modification begin. Some of these proteins are incorporated into membrane, and
some are for export. Smooth ER, which is continuous with rough ER, does not have
attached ribosomes
• Smooth ER synthesizes the phospholipids that occur in membranes and has
various other functions, depending on the particular cell
- In the testes, it produces testosterone, and in the liver it helps detoxify drugs

24
Cellular Organization

Mitochondria
• Are bounded by a double membrane
• The inner membrane is folded to form little shelves called cristae, which project
into the matrix, an inner space filled with a gel-like fluid
• Mitochondria are the site of ATP (adenosine triphosphate) production involving
complex metabolic pathways
- ATP molecules are the common carriers of energy in cells
• *

25
Cellular Organization
Mitochondria
• The mitochondrion is often called the powerhouse of the cell
• Just as a powerhouse burns fuel to produce electricity, the mitochondria convert the
chemical energy of carbohydrate molecules into the chemical energy of ATP
molecules
• In the process, mitochondria use up oxygen and give off carbon dioxide and water

• The oxygen you breathe in enters cells and then mitochondria; the carbon dioxide
you breathe out is released by mitochondria
- Because oxygen is used up and carbon dioxide is released, we say that mitochondria
carry on cellular respiration
26
Cellular Organization

Mitochondria
• Fragments of digested carbohydrate, protein, and lipid enter the mitochondrial
matrix from the cytoplasm
• The matrix contains enzymes for metabolizing these fragments to carbon dioxide
and water
• Energy released from metabolism is used for ATP production, which occurs at the
cristae
- The protein complexes that aid in the conversion of energy are located in an assembly-
line fashion on these membranous shelves
• Many cells use ATP to carry out their specialized functions
- For example, muscle cells use ATP for muscle contraction, which produces movement,
and
- nerve cells use it for the conduction of nerve impulses, which make us aware of our
environment

27
Cellular Organization
The Cytoskeleton
• Several types of filamentous protein structures form a cytoskeleton, and this helps
to maintain the shape of the cell, and either anchors the organelles or assists
their movement as appropriate
• The cytoskeleton includes microtubules, intermediate filaments, and actin filaments

a. Microtubules are hollow cylinders whose wall is made up of 13 longitudinal rows


of the globular protein tubulin
• Microtubules can assemble and disassemble, an the assembly process is regulated
by the centrosome, which lies near the nucleus. The centrosome is the region of
the cell that contains the centrioles
• Microtubules radiate from the centrosome, helping to maintain the shape of the cell
and acting as tracks along which organelles move
• During cell division, microtubules form spindle fibers, which assist the movement of
chromosomes

28
Cellular Organization
The Cytoskeleton

b. Intermediate filaments differ in structure and function. Because they are tough
and resist stress, intermediate filaments often form cell-to-cell junctions
• Intermediate filaments join skin cells in the outermost skin layer, the epidermis

c. Actin filaments are long, and extremely thin fibers that usually occur in bundles
or groups
• Actin filaments have been isolated from various types of cells, especially those in
which movement occurs
• Microvilli, which project from certain cells and can shorten and extend, contain actin filaments.
Actin filaments, like microtubules, can assemble and disassemble

29
DISCUSSION

30
TRANSPORT ACROSS THE PLASMA MEMBRANE

• The plasma membrane keeps the content of a cell intact


• It is selectively permeable, and therefore, allows only certain molecules and ions
to enter and exit the cytoplasm freely
• Both passive and active transport methods are used to cross the plasma
membrane

31
Transport across the plasma membrane
Simple Diffusion
• Diffusion is the spontaneous movement of simple atoms or molecules from an
area of higher concentration to an area of lower concentration until they are
equally distributed
• Eventually eliminating the concentration difference between the two regions
- To illustrate diffusion, imagine putting a tablet of dye into water
- The water eventually takes on the color of the dye as the dye molecules diffuse

32
Transport across the plasma membrane

Simple Diffusion
• The chemical and physical properties of the plasma membrane allow only a few
types of molecules to enter and exit a cell by simple diffusion
- However, lipid-soluble molecules such as alcohols can diffuse through the membrane
because lipids are the membrane’s main structural components

• Gases can also diffuse through the lipid bilayer; this is the mechanism by which
oxygen enters cells and carbon dioxide exits cells
- For example, consider the movement of oxygen from the lungs to the bloodstream
- When you inhale, oxygen fills the tiny air sacs (alveoli) within your lungs. Neighboring
lung capillaries contain red blood cells with a very low oxygen concentration
- Oxygen diffuses from the area of higher (oxygen) concentration to the area of lower
(oxygen) concentration: first through alveolar cells, then lung capillary cells, and
finally into the red blood cells

33
Transport across the plasma membrane

Simple Diffusion
• When atoms or molecules diffuse from areas of higher to lower concentration
across plasma membranes, no cellular energy is involved
• Instead, kinetic or thermal energy of matter is the energy source for diffusion

34
Transport across the plasma membrane
Osmosis
• In osmosis, there is the movement of solvent molecules across a
semipermeable membrane, from a region of higher water concentration to a
region of lower water concentration

• Water molecules move more rapidly through the membrane of a cell than
dissolved ions or small polar organic solutes, which are considered
nonpenetrating
- Because of this difference in the penetrability of water versus solutes through the
plasma membrane, the membrane is said to be semipermeable

35
Transport across the plasma membrane

Osmosis
• Osmosis occurs whenever an unequal concentration of water exists on either
side of a selectively permeable membrane
- In a solution, water is more concentrated when it contains fewer dissolved
substances, or solutes, (and thus is closest to pure water)
- Water is less concentrated as solute concentration increases

• (Recall that a selectively permeable membrane allows water to pass freely, but
not most dissolved substances)

• Osmotic pressure is the force exerted on a selectively permeable membrane


when water moves from an area of higher water concentration (lower solute
concentration) to an area of lower water concentration (higher solute
concentration)

36
Transport across the plasma membrane

Osmosis

• When two compartments of different solute concentration are separated by a


semipermeable membrane, the compartment of higher solute concentration is
said to be hypertonic (or hyperosmotic),
• whereas, the compartment with lower solute concentration, which is described as
being hypotonic (or hypoosmotic)
• Once the internal solute concentration of a cell equals the external solute
concentration, the internal and external fluids are isotonic (or isosmotic), and
no net movement of water into or out of the cells occurs
• When a cell is placed into a hypotonic solution, the cell rapidly gains water by
osmosis and swells

37
Transport across the plasma membrane

Osmosis

• Conversely, a cell placed into a hypertonic solution rapidly loses water by


osmosis and shrinks
• By these simple observations, it is evident that the volume of a cell is
controlled by the difference between the solute concentration inside the cell
and that in the extracellular medium

38
Transport across the plasma membrane
Osmosis
(a) A cell placed in a
hypotonic solution (one
having a lower solute
concentration than the cell)
swells because of a net gain
of water by osmosis

(b) A cell in a hypertonic


solution shrinks because of a
net loss of water by osmosis

(c) A cell placed in an isotonic


solution maintains a constant E.g. Your digestive tract, for example, secretes several
volume because the inward liters of fluid daily, which is reabsorbed osmotically by
flux of water is equal to the the cells that line your intestine
outward flux
39
Transport by Carriers

Facilitated Transport
• Substances always diffuse across the plasma membrane, when the concentrations
of substances on either sides/regions of the membrane are different
• However, most solutes do not simply diffuse across a plasma membrane
- Also, they do not always diffuse through the lipid bilayer or through a channel
- Instead, they are transported by means of protein carriers within the membrane

• In facilitated transport (facilitated diffusion), solute molecules (e.g., an amino


acids or glucose) are transported across the plasma membrane from the side of
higher concentration to the side of lower concentration

• The cell does not require energy for this type of transport because the molecules
are moving down their concentration gradient

40
Transport by Carriers

Facilitated Transport

• Facilitated diffusion mediates the entry and exit of polar solutes, such as sugars
and amino acids, that do not penetrate the lipid bilayer

• Unlike ion channels, which can conduct millions of ions per second, most
facilitative transporters can move only hundreds to thousands of solute molecules
per second across the membrane

• The activity of facilitative transporters can be regulated, like enzymes and ion
channels

41
Transport by Carriers

Facilitated Transport
• In many cases, the diffusing
substance first binds selectively to a
membrane-spanning protein, called
a facilitative transporter, that
facilitates the transport/diffusion
process

• Facilitated diffusion is similar in


many ways to an enzyme-catalyzed
reaction. Just like enzymes,
facilitative transporters are specific
for the molecules they transport, and
are able to discriminate between
non-specific solute molecules
42
Transport by Carriers

Active Transport
• This is an energy-driven process where membrane proteins transport molecules
or ions across a cell membrane from a region of lower concentration to a region of
higher concentration, against the concentration gradient

• Active transport requires a protein carrier and the use of cellular energy obtained
from the breakdown of ATP

• Proteins involved in active transport are often called pumps


- because just as a water pump uses energy to move water against the force of gravity,
proteins use energy to move substances against their concentration gradients

- There is one type of pump that is active in all cells but is especially associated with
nerve and muscle cells
- This pump moves sodium ions (Na+) to the outside of the cell and potassium ions (K+) to
the inside of the cell
*

43
Transport by Carriers

Active Transport
• When ATP is broken down, energy is released, and in this case the energy is
used by a carrier to carry out active transport
• Therefore, cells involved in active transport have a large number of mitochondria
near the plasma membrane at which active transport is occurring

44
DISCUSSION

45
Transport across the plasma membrane

Endocytosis and Exocytosis


• The carrier and channel proteins discussed in the preceding slides transport
small molecules through the phospholipid bilayer

• Eukaryotic cells are also able to ingest large particles (such as bacteria) and
the uptake of fluids or macromolecules in small vesicles from the surrounding
medium by a distinct process called endocytosis

• During endocytosis, a portion of the plasma membrane forms an inner pocket


to engulf (envelop) a substance, and the membrane then buds off to form an
intracellular vesicle containing the ingested material

46
Transport across the plasma membrane

Endocytosis and Exocytosis


Two forms of endocytosis exist: (1) Phagocytosis and (2) Pinocytosis
• Phagocytosis (cell eating) occurs largely in specialized types of cells, whereas,
other forms of endocytosis take place in all eukaryotic cells
• Phagocytosis, or “cell eating,” is a mechanism whereby the cell can ingest solid
particles
- White blood cells consume bacterial cells by phagocytosis. Once inside the cell, the
bacterial cell can be destroyed
• Pinocytosis, or “cell drinking,” allows the cell to consume solutions
- An infant’s intestinal lining ingests breast milk by pinocytosis, allowing the mother’s
protective antibodies to enter the baby’s bloodstream

• During exocytosis, a vesicle fuses with the plasma membrane as secretion occurs

47
Transport across the plasma membrane

48

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