Cell biology

Peris Moraa Mokua

CELL BIOLOGY

General introduction

Biology: is the study of living organisms.

Cell biology: is the biological science that entails the study of structure, function, molecular

organization, growth and genetics of cells. The great percentage of study is devoted to the

study of structures and functions of specialized cells.

Cell: is the basic unit of life. They are tiny and complex bodies. Hence it is difficult to see

their structure, understand their molecular composition and further to discern the various

functions of their components.

Life begins with cells

Like ourselves, the individual cells that form our bodies can grow, reproduce, process

information, respond to stimuli, and carry out an amazing array of chemical reactions. These

abilities define life. We and other multicellular organisms contain billions or trillions of cells

organized into complex structures, but many organisms consist of a single cell. Even simple

unicellular organisms exhibit all the hallmark properties of life, indicating that the cell is the

fundamental unit of life.

THE CELL

Cell is the basic structural and functional unit of all known living organisms. It can also be

defined as Basic unit of life

Most plant and animal cells are tiny/small size and are visible only under the microscope:-

 1-100µm in size

 Prokaryotic: 1-10 μm

 Eukaryotic: 10 - 100 μm

 Where 1 μm = .001 mm

All living things are made of cells: 1 or >1

Bacteria are unicellular organisms, but humans are multicellular (hierarchy:

body>organ>tissue>cell).

Characteristics of cells

1. Cells as open systems: a cell is an open system which exchanges both matter and

energy with its environment.

2. Cells are self-regulating system: cells functions on maximum economy basis hence

reactions must be self-regulatory and self-controlled.

3. Cells are self-replicating system: reproduction; cell division

PHYSIOLOGICAL SIGNIFICANCE OF CELL SIZE

As cell size increases the volume increases much faster than the surface area. Cells obtain

nutrients, gain information and get rid of waste through their plasma membrane. As cell size

increases, a cell’s ability to exchange with its environment becomes limited by the amount of

membrane area that is available for exchange.

Peris Moraa Mokua

Why are cells so small?

 To have increased surface area to volume ratio so as to use simple mechanisms to

obtain/get rid of nutrients/wastes respectively

 Enable them to penetrate places

 Easy to divide

 So as many cells can occupy a small volume; tissues, organ size

DISCOVERY OF CELLS

1665- English Scientist, Robert Hooke, discovered cells while looking at a thin slice of cork

(Obtained from a bark of a tree). He observed small boxes and called them cells. He

described the cells as tiny boxes or a honeycomb. He thought that cells only existed in plants

and fungi

Anton van Leuwenhoek

 1673- Used a handmade microscope to observe pond scum & discovered single-

celled organisms

 He called them “animalcules”

 He also observed blood cells from fish, birds, frogs, dogs, and humans

 Therefore, it was known that cells are found in animals as well as plants

150-200 Year Gap

 Between the Hooke/Leuwenhoek discoveries and the mid-19th century, very little cell

advancements were made.

 This is probably due to the widely accepted, traditional belief in Spontaneous

Generation. Examples:

 Mice from dirty clothes/corn husks

 Maggots from rotting meat

 Much doubt existed around Spontaneous Generation

From 1824 to 1830

Works of Dutrochet, Turpin, and Meyers among others not only confirmed the universality of

cellular structure but also hinted at the concept of cellular autonomy in both the

morphological and physiological sense

Discovery of the Nucleus

Robert Brown (1831) was the first to report the discovery the nucleus of the cell.

1832: Dumortier reported on cell division in algae, and from 1835 to 1839, von Mohl

sketched many features of mitosis.

These workers might be considered founders of the specialized aspect of cytology sometimes

known as karyology

Peris Moraa Mokua

DEVELOPMENT OF CELL THEORY

1838- German Botanist, Matthias Jakob Schleiden, concluded that all plant parts are

made of cells

1839- German physiologist, Theodor Schwann, who was a close friend of Schleiden, stated

that all animal tissues are composed of cells.

1858- Rudolf Virchow, German physician, after extensive study of cellular pathology, he

concluded that cells must arise from preexisting cells.

Components of the Cell Theory

The 3 Basic Components of the Cell Theory were now complete: that’s

1. All organisms are composed of one or more cells.

2. The cell is the basic unit of life in all living things.

3. All cells are produced by the division of preexisting cells.

Modern Cell Theory

Modern Cell Theory contains 4 statements, in addition to the original Cell Theory:

 The cell contains hereditary information (DNA) which is passed on from cell to cell

during cell division.

 All cells are basically the same in chemical composition and metabolic activities.

 All basic chemical & physiological functions are carried out inside the cells

(movement, digestion, etc.)

 Cell activity depends on the activities of sub-cellular structures within the cell

(organelles, nucleus, plasma membrane)

Uses of Cell Theory

 The basic discovered truths about cells, listed in the Cell Theory, are the basis for

things such as: Disease/Health/Medical Research and Cures (AIDS, Cancer, Vaccines,

Cloning, Stem Cell Research, etc.)

TYPES OF CELLS

There are two major types of cells: The Prokaryotic cell and The Eukaryotic cells

Prokaryotic and eukaryotic. "Karyose" comes from a Greek word which means "kernel," as in

a kernel of grain. In biology, one use this word root to refer to the nucleus of a cell. "Pro"

means "before," and "eu" means "true," or "good." So "Prokaryotic" means "before a

nucleus," and "eukaryotic" means "possessing a true nucleus."

Prokaryotic cells have no nuclei, while eukaryotic cells do have true nuclei. This is far

from the only difference between these two cell types.

Peris Moraa Mokua

Prokaryotic cells

 Consist of simple closed compartment that is surrounded by the plasma membrane

 They lack a defined nucleus

 Their internal organization is simple with no organelles

Prokaryotes with this kind of organization include:

 Bacteria

 Cyano-bacteria

 Blue green algae

Prokaryotic cell structure

Fig. 1: Structure of prokaryotic cell

Eukaryotic cells

 Are larger, with a typical plasma membrane - some with a cell wall

 Have many organelles and other interior spaces enclosed by membranes:

Examples of organelles: Nucleus, Endoplasmic reticulum, Golgi apparatus, Mitochondria,

Chloroplasts, Lysosomes,Vacuoles, Vesicles

 They have a cytoplasm with a cytoskeleton - protein tubules and fibers

 Eukaryotic plant cells have a ell wall made of cellulose, fungi (chitin), some protists.

Animal cell Plant cell

Peris Moraa Mokua

Fig.2 : Structure of eukaryotic cells

Similarities between Prokaryotic and Eukaryotic cells

 Both are enclosed by plasma membranes, filled with cytoplasm, and loaded with

small structures called ribosomes.

 Both have DNA which carries the archived instructions for operating the cell.

 And the similarities go far beyond the visible-physiologically they are very similar in

many ways. For example, the DNA in the two cell types is precisely the same kind of

DNA, and the genetic code for a prokaryotic cell is exactly the same genetic code

used in eukaryotic cells.

Some things which seem to be differences aren't. For example, the prokaryotic cell has a cell

wall, and this animal cell does not. However, many kinds of eukaryotic cells do have cell

walls.

Peris Moraa Mokua

Table 1: Differences between prokaryotic and Eukaryotic cells

 Eukaryotic cells are much larger and much more complex than prokaryotic cells.

These two observations are not unrelated to each other.

 Eukaryotic cells have a true nucleus, bound by a double membrane. Prokaryotic cells

have no nucleus.

 Eukaryotic DNA is complexed with proteins called "histones," and is organized into

chromosomes; prokaryotic DNA is "naked," meaning that it has no histones

associated with it, and it is not formed into chromosomes.

 A eukaryotic cell contains a number of chromosomes; a prokaryotic cell contains only

one circular DNA molecule and a varied assortment of much smaller circlets of DNA

called "plasmids." The smaller, simpler prokaryotic cell requires far fewer genes to

operate than the eukaryotic cell.

 Both cell types have many, many ribosomes, but the ribosomes of the eukaryotic cells

are larger and more complex than those of the prokaryotic cell. A eukaryotic ribosome

is composed of five kinds of rRNA and about eighty kinds of proteins. Prokaryotic

ribosomes are composed of only three kinds of rRNA and about fifty kinds of protein.

 The cytoplasm of eukaryotic cells is filled with a large, complex collection of

organelles, many of them enclosed in their own membranes; the prokaryotic cell

contains no membrane-bound organelles which are independent of the plasma

membrane.

CELL ORGANELLES

An organelle is a membrane bound structure found within a cell. Organelles are found in the

cytoplasm, a viscous liquid found within the cell membrane that houses the organelles and is

the location of most of the action happening in a cell.

Advantages of Membrane Bound Organelles

 Many metabolic processes involve membrane embedded enzymes

Peris Moraa Mokua

 Enzymes of a particular pathway are within organelles thus products are within

proximity

 Potentially harmful reactants and products are in isolation hence won‘t damage the

rest of the cell.

Main components of Eukaryotic cell (plant/animal cell)

1. Cytoplasm- The jelly-like substance composed of mainly water and found between

the cell membrane and nucleus. Makes up most of the "body" of a cell and is

constantly streaming. Organelles are found here and substances like salts may be

dissolved in the cytoplasm.

2. Nucleus- Contains genetic information (DNA) on special strands called

chromosomes. The nucleus is the "control center" of the cell, for cell metabolism

and reproduction.

3. Plasma membrane/ cell membrane- Separates the cell from its external environment,

selectively permeable. Protects the cell and provides stability.

NUCLEUS

 Is the largest organelle in the cell- controls cell activities. It is dark and round, and is

surrounded by a double membrane called the nuclear envelope/membrane. The

nuclear envelop creates a room within the cell to both protect the genetic information

and to house all the molecules that are involved in processing and protecting that info.

It also keeps molecules responsible for DNA transcription and repair close to the

DNA itself

 In spots the nuclear envelope fuses to form nuclear pores which are selectively

permeable- control entry and exit of materials.

 The nucleus contains the nucleolus, a darkened region where formation of ribosomes

and ribosomal RNA synthesis takes place.

 It also contains genetic information (DNA) on special strands called chromosomes

(tightly packed strands of DNA containing all our blueprints). Chromosomes are

found in the nucleoplasm (fluid that fills nucleus) which is similar in structure and

function to cytoplasm. They consist of both DNA and protein which are seen as

chromosomes when highly condensed in preparation for cell division. At other times

they are threadlike and called chromatins. Histones are the most common proteins.

DNA is coiled around histones in a regular pattern which produce structures called

nucleosomes.

Functions

 The nucleus is the "control center" of the cell, for cell metabolism and reproduction.

 Separate DNA from the rest of the cell.

 Transcription (making a complementary strand of RNA from DNA)

Peris Moraa Mokua

Fig. 3: Structure of nucleus

CYTOPLASM

Cytoplasm is the internal volume bounded by the plasma membrane. Is also a clear fluid in

the cytosol where particles are suspended. Translation (protein synthesis from RNA) takes

place in the cytoplasm. It contains:

 Dissolved proteins

 Electrolytes

 Glucose

 Organelles e.g Endoplasmic reticulum (ER), golgi apparatus, mitochondria,

lysosomes, peroxisomes, ribosomes, chloroplasts.

Endoplasmic Reticulum (E.R)

Endoplasmic means inside (endo) the cytoplasm (plasm). Reticulum comes from the Latin

word for net. Basically, an endoplasmic reticulum is a plasma membrane found inside the cell

that folds in on itself to create an internal space known as the lumen. The ER is a network of

membranous canals within the cytoplasm. They look like flattened sheets, sacs, tubes. They

create many membrane enclosed spaces spread across the cytoplasm. ER has connections

with the outer membrane of the nucleus and the plasma membrane. It has an interior space

called cisternae filled with fluid called endoplasmic matrix.

Types of ER

There are two types of ER: Rough ER and Smooth ER.

a) Rough ER: Is studded (lined) with ribosomes (the molecules in charge of protein

production) and is rough in appearance. The rough ER is continuous with the nuclear

envelope, and looks like a series of canals near the nucleus.

Function:

 Site of synthesis of many proteins- Proteins made in the rough ER are destined to

either be a part of a membrane, or to be secreted from the cell membrane out of the

cell. Without a rough ER, it would be a lot harder to distinguish between proteins that

should leave the cell, and proteins that should remain.

 Helps cells specialize and allows for greater complexity in the organism.

Peris Moraa Mokua

b) Smooth ER- Contains no ribosomes and is smooth in appearance. It is more tubular than

the rough ER, and is not necessarily continuous with the nuclear envelope. Every cell has a

smooth ER, but the amount will vary with cell function. For example, the liver, which is

responsible for most of the body’s detoxification, has a larger amount of smooth ER.

Fuctions:

 Site for synthesis of steroids and other lipids- These are fat-based molecules that are

important in energy storage, membrane structure, and communication (steroids can

act as hormones).

 Detoxifying the cell of drugs, toxins, alcohol (especially the liver)

 Ca++ storage in muscles

 The highly convoluted surface provides a large surface area for enzymatic activities.

Many enzymes are imbedded in the membranes.

Fig. 4: Structure of ER

Ribosomes

Ribosomes are small particles which are found individually in the cytoplasm and also line the

membranes of the rough endoplasmic reticulum.

 Ribosomes are protein synthesis machinery i.e they produce proteins.

 They are composed of two subunits, large and small, each made of protein and

ribosomal RNA (rRNA).The subunits associate when they are synthesizing proteins.

Peris Moraa Mokua

Fig. 5: Structure of the ribosome

 Protein synthesis occurs on ribosomes that are free-floating in the cytoplasm and on

ribosomes attached to ER.

 rRNA is synthesized in the nucleolus ( a small subspace within the nucleus).

The figure below shows ribosomes attached to membrane of ER.

Fig. 6: Ribosomes attached to the membrane of ER

Golgi apparatus

Are also called Golgi bodies or Golgi. They are stacks of flattened membranous stacks. They

are present in all cells except the RBCs.

Functions: Is functionally associated with the ER.

 Packing proteins from the rough ER into membrane-bound vesicles (tiny

compartments of lipid bilayer that store molecules) which then translocate to the cell

membrane

 Temporarily stores protein which can then leave the cell via vesicles pinching off

from the Golgi.

Different molecules have different fates upon entering the Golgi. This determination is done

by tagging the proteins with special sugar molecules that act as a shipping label for the

protein. The “shipping department” identifies the molecule and sets it on one of 4 paths:

Peris Moraa Mokua

1. Cytosol: the proteins that enter the Golgi by mistake are sent back into the cytosol).

2. Cell membrane: proteins destined for the cell membrane are processed continuously.

Once the vesicle is made, it moves to the cell membrane and fuses with it. Molecules

in this pathway are often protein channels which allow molecules into or out of the

cell, or cell identifiers which project into the extracellular space and act like a name

tag for the cell.

3. Secretion: some proteins are meant to be secreted from the cell to act on other parts

of the body. Before these vesicles can fuse with the cell membrane, they must

accumulate in number, and require a special chemical signal to be released.

4. Lysosome: The final destination for proteins coming through the Golgi is the

lysosome. Vesicles sent to this acidic organelle contain enzymes that will hydrolyze

the lysosome’s content.

Mitochondria

The mitochondria are round "tube-like" organelles that are surrounded by a double

membrane, Inner and outer membranes. The inner membrane is highly folded into inward

projections called cristae- increases surface area for the site of reactions. Mitochondria are

often referred to as the "powerhouse" of the cell (releases food energy from food molecules to

be used by the cell in a process called respiration. There are two spaces within the

mitochondrion - the matrix and intermembrane space.

Unique features of mitochondria

 Have their own DNA (almost as if they were a completely separate cell) that is similar

to prokaryotic DNA

 Have their own ribosomes that are similar in construction to prokaryotic ribosomes

o Synthesize many, but not all, of their own proteins

 Mitochondria are self-replicating i.e replicate by binary fission - similar to prokaryotic

cell division

Fig. 7: Structure of Mitochondria

Peris Moraa Mokua

Lysosomes

The lysosome is the cell’s recycling center. They are vescular organelles formed from golgi

and dispersed throughout the cytoplasm. They are also called suicide sacs.

They contain digestive and hydrolytic enzymes that digest food (carbohydrates, proteins,

lipids), nucleic acids and part of the cell-worn-out organelles.

Lysosomal proteins only being active in an acidic environment acts as safety mechanism for

the rest of the cell - if the lysosome were to somehow leak or burst, the degradative enzymes

would inactivate before they chopped up proteins the cell still needed.

They are also covered by a thick membrane-prevents enclosed hydrolytic enzymes from

coming in contact with other substances in the cell thus preventing their digestive actions.

Functions:

 Destruct foreign materials-bacteria

 Removal of excessive secretory products in cells of the glands

 Removal of unwanted cells in embryo

Peroxisome

The peroxisome is a spherical organelle responsible for destroying its contents.

Functions

 Unlike the lysosome, which mostly degrades proteins, the peroxisome is the site of

fatty acid breakdown.

 It also protects the cell from reactive oxygen species (ROS) molecules which could

seriously damage the cell. ROSs are molecules like oxygen ions or peroxides that are

created as a by-product of normal cellular metabolism, but also by radiation, tobacco,

and drugs. They cause what is known as oxidative stress in the cell by reacting with

and damaging DNA and lipid-based molecules like cell membranes. These ROSs are

the reason we need antioxidants in our diet.

Vacuoles

Vacuoles are fluid filled organelles enclosed by a membrane. They can store materials such

as food, water, sugar, minerals and waste products.

Animal cell organelles not found in plant cells:

Cilia and flagella

Both cilia and flagella are hair-like organelles which extend from the surface of many animal

cells. The structure is identical in both, except that flagella are longer and whiplike and cilia

are shorter. There are usually only a few flagella on a cell, while cilia may cover the entire

surface of a cell.

Functions

 Locomotion for one-celled organisms

 Move substances over cell surfaces in multi-celled organisms.

Organelles and other features found only in plant cells:

Peris Moraa Mokua

1. Cell wall

The cell wall is a rigid organelle composed of cellulose and lying just outside the cell

membrane. The cell wall gives the plant cell its box-like shape. It also protects the cell. The

cell wall contains pores which allow materials to pass to and from the cell membrane.

2. Plastids

Plastids are double membrane bound organelles. It is in plastids that plants make and store

food. Plastids are found in the cytoplasm and there are two main types: Pigmented and non-

pigmented plastids:

a) Leucoplasts - colorless organelles which store starch or other plant nutrients.

(Example - starch stored in a potato)

b) Chromoplasts - contain different colored pigments. The most important type of

chromoplast is the chloroplast, which contains the green pigment chlorophyll. This

is important in the process of photosynthesis.

 Chloroplasts

Are sites of photosynthesis - in nearly all plants and some protists.

Functions

 They trap light energy and convert it into chemical energy to create food by

photosynthesis. Synthesize and store starch in roots and tubers.

 They have pigments and give fruits ripened color.

Characteristics of Chloroplasts

 They have a double membrane structure with an inner space called the stroma.

 Have their own DNA, similar to prokaryotic DNA.

 They can synthesize many of their own proteins using prokaryote-like ribosomes.

 Replicate through division similar to prokaryotic cell division

PLASMA MEMBRANE STRUCTURE AND FUNCTION

Introduction

Cell membrane-also known as plasma membrane (PM) is a thin biological membrane that

surrounds the cytoplasm of the cell. It also separates the interior of all cells from the outside

environment and divides the interior of the cell into compartments:

 Fluid outside the cell, Extracellular fluid (ECF)

 Fluid inside the cell, Intacellular Fluid (ICF).

The PM is selectively permeable to ions and organic molecules and controls the movement of

subastances in and out of cells. The basic function of the cell membrane is to protect the cell

from its surroundings.

Functions of the Plasma Membrane

 Protect the integrity of the interior of the cell by allowing certain substances into the

cell, while keeping other substances out.

 The outer plasma membrane forms a boundary between a living cell and its

surroundings; Exhibits selective permeability, Controls traffic of molecules in and

out.

Peris Moraa Mokua

 Internal membranes provide structural order for metabolism. Form the cell's

organelles. Compartmentalize chemical reactions, organizes the chemical activities of

cells.

 It serves as a base of attachment for the cytoskeleton in some organisms and the cell

wall in others.

 It helps support the cell and help maintain its shape and size.

 Regulate cell growth through the balance of endocytosis and exocytosis. In

endocytosis, lipids and proteins are removed from the cell membrane as substances

are internalized. In exocytosis, vesicles containing lipids and proteins fuse with the

cell membrane increasing cell size.

 Encased internal organelles.

 Communication

 Recognition

 Cell membranes are involved in a variety of cellular processes such as cell adhesion,

ion conductivity and cell signalling.

Structure of the Plasma Membrane

Fluid Mosaic Model

The currently accepted model for the structure of the plasma membrane, called the fluid

mosaic model, was first proposed in 1972. This model has evolved over time, but it still

provides a good basic description of the structure and behavior of membranes in many cells.

According to the fluid mosaic model, the plasma membrane is a mosaic of components—

primarily, phospholipids, cholesterol, and proteins—that move freely and fluidly in the plane

of the membrane. Proteins and other molecules are embedded in a framework of

phospholipids. Most proteins and phospholipid molecules can move laterally. The fluid

nature of the PM is important for normal functioning.

Chemical Composition

The principal components of the plasma membrane are lipids (phospholipids and cholesterol),

proteins, and carbohydrate groups that are attached to some of the lipids and proteins.

 A phospholipid is a lipid made of glycerol, two fatty acid tails, and a phosphate-

linked head group. Biological membranes usually involve two layers of phospholipids

with their tails pointing inward, an arrangement called a phospholipid bilayer.

 Cholesterol, another lipid composed of four fused carbon rings, is found alongside

phospholipids in the core of the membrane.

 Membrane proteins may extend partway into the plasma membrane, cross the

membrane entirely, or be loosely attached to its inside or outside face.

 Carbohydrate groups are present only on the outer surface of the plasma membrane

and are attached to proteins, forming glycoproteins, or lipids, forming glycolipids.

1. Membrane Lipids

They are organized into lipid bilayer. Major classes of membrane lipids include:

 Phospholipids

 Glycolipids

 Cholesterol: stability to the membrane

Peris Moraa Mokua

Phospholipids: Phospholipids, arranged in a bilayer, make up the basic fabric of the plasma

membrane. They are well-suited for this role because they are amphipathic, meaning that

they have both hydrophilic and hydrophobic regions.

The hydrophilic, or “water-loving,” portion of a phospholipid is its head, which contains a

negatively charged phosphate group as well as an additional small group which may also or

be charged or polar. The hydrophilic heads of phospholipids in a membrane bilayer face

outward, contacting the aqueous (watery) fluid both inside and outside the cell. Since water is

a polar molecule, it readily forms electrostatic (charge-based) interactions with the

phospholipid heads.

The hydrophobic, or “water-fearing,” part of a phospholipid consists of its long, nonpolar

fatty acid tails. The fatty acid tails can easily interact with other nonpolar molecules, but they

interact poorly with water. Because of this, it’s more energetically favourable for the

phospholipids to tuck their fatty acid tails away in the interior of the membrane, where they

are shielded from the surrounding water. The phospholipid bilayer formed by these

interactions makes a good barrier between the interior and exterior of the cell, because water

and other polar or charged substances cannot easily cross the hydrophobic core of the

membrane.

Functions

 Provide membrane with form

 Selective barrier

Fig. 8: Phospholipid structure

2. Membrane Proteins

Proteins are the second major component of plasma membranes. There are two main

categories of membrane proteins: Integral and Peripheral.

a) Integral/Intrinsic membrane proteins: Are partially or fully immersed/integrated into

the lipid bilayer. They have at least one hydrophobic region that anchors them to the

hydrophobic core of the phospholipid bilayer. Some stick only partway into the membrane,

while others stretch from one side of the membrane to the other and are exposed on either

side. Proteins that extend all the way across the membrane are called transmembrane

proteins.

Peris Moraa Mokua

The portions of an integral membrane protein found inside the membrane are hydrophobic,

while those that are exposed to the cytoplasm or extracellular fluid tend to be hydrophilic.

Transmembrane proteins may cross the membrane just once, or may have as many as twelve

different membrane-spanning sections. Some integral membrane proteins form a channel that

allows ions or other small molecules to pass.

Function as: Channels, Carrier proteins, Enzymes, Receptors and Support.

b) Peripheral/Extrinsic membrane proteins: Are found on the outside and inside surfaces

of membranes, attached either to integral proteins or to phospholipids by hydrogen or

electrostatic bonds. Unlike integral membrane proteins, peripheral membrane proteins do not

stick into the hydrophobic core of the membrane, and they tend to be more loosely attached.

Functions: Enzymes, Receptors

Fig. 9: Lipid bilayer with membrane proteins

3. Membrane Carbohydrates

Are the third major component of plasma membrane. They are found on the outside surface

of cells and are bound either to proteins (forming glycoproteins) or to lipids (forming

glycolipids). These carbohydrate chains may consist of 2-60 monosaccharide units and can be

either straight or branched.

Functions

 Along with membrane proteins, these carbohydrates form distinctive cellular markers

that allow cells to recognize each other. These markers are very important in the

immune system, allowing immune cells to differentiate between body cells, which

they shouldn’t attack, and foreign cells or tissues, which they should.

 Carbohydrates negatively charged, Membrane negative charge; Repel negatively

charged molecules

 Act as receptor site

 Attachment to other cells

Peris Moraa Mokua

Fig. 10: Plasma Membrane Structure

Movement of Substances Across the Plasma Membrane

The PM is differentially permeable: some substances readily pass through, others do not. It is

most permeable to small molecules and lipid-soluble substances. Water(!) and other small

molecules like CO2 and O2 can pass through easily. There are molecules that do not pass

through easily: amino acids, sugars, ions. Passage of some molecules across the membrane is

assisted with special channels to allow or speed up the passage. The specific selectivity can

vary depending on the membrane.

There are two different types of exchange of molecules between the outside and inside of the

cell.

1. Passive transport- Movement of substances is due to gradient differences in

concentration, pressure and charge. There are 3 forms:

-Diffusion

-Faciliatetd transport; Uniport transport

-Osmosis

2. Active transport; Movement of substances through the cell mebrane that require use of

energy (ATP).

-Sodium-Potassium pump

-Endocytosis

-Exocytosis

-Symport transport systems

-Antiport transport systems

1. Passive Transport

a) Diffusion

Is the random movement of molecules from the area of higher concentration to the area of

lower concentration (net movement), until they are equally distributed. Examples: Sugar in

tea (We stir the tea to speed up the diffusion). The odour of food cooking, perfumes etc. CO2

entering the stomata of leave. Oxygen diffusing out of the stomata and lenticels of leaves

Peris Moraa Mokua

Factors Affecting the Rate of Diffusion

 Concentration gradient difference

 Distance over which diffusion takes place

 The area over which diffusion takes place-surface area

 The nature of any structure across which diffusion occurs e.g number of pores

 The size and nature of the diffusing molecules

o Small in size and Fat soluble diffuse faster

b). Osmosis

Movement of water molecules from a region of higher concentration to a region of low

concentration through a semi-permeable membrane. Movement of substances from more

dilute solution to a more concentrated solution (solvent particles are moving from higher to

lower solvent concentration across the membrane, they are moving from lower to higher

solute concentration). Example; Absorption of water by plant roots.

The movement of liquids in and out cells is dependent on the concentration of the solution

surrounding it. There are 3 types of situations in which this could vary:

1. Isotonic: External solution concentration and the internal concentration of the organism

are the same i.e. there is the same concentration of non-diffusible solutes and water on both

sides of the plasma membrane.

2. Hypotonic: External solution concentration is less than the concentration of the organism

i.e. concentration of solutes is lower outside the cells In this case water will rush into the

organism.

3. Hypertonic: External solution concentration is greater than the concentration of the

organism i.e. the concentration of solutes is higher outside the cells In this case the water will

rush out of the organism.

Peris Moraa Mokua

Table 2: Differences between diffusion and osmosis

Diffusion

Osmosis

Movement of all types of substances from the

area of their higher free energy to the area of

their lower free energy

Movement of only solvent or water from its

higher concentration to lower concentration

across a membrane

Can operate in any medium

Operates only in a liquid medium

Applicable to all types of substances; solid,

liquid, gases

Applicable to only solvent part of the

solution

Does not require any semi-permeable

membrane

Requires a semi-permeable membrane

Turgor pressure does not normally operate in

diffusion

Is opposed by turgor pressure of the system

Not influenced by solute potential

Dependent upon the solute potential

Diffusion of a substance mostly dependent of

the presence of other substances

Osmosis is dependent upon the number of

particles of the other substances dissolved in

the liquid

c) Facilitated Transport

Non-diffusible solutes such as sugars or amino acids can be transported by means of protein

carriers in the plasma membrane at a rate higher than usual across the plasma membrane from

the side of higher concentration to the side of lower concentrations. Each protein carrier is

sometimes called ‘transporter’. Energy – not necessary.

Fig. 11: Facilitated diffusion

2. Active Transport

A molecule moves from lower concentration to a higher concentration by means of ‘pump’.

Thus, the solute can be concentrated in either side. Energy in form of ATP is necessary.

Fig. 12: Active transport

a) Endocytosis

Is the movement of large material examples particles, organisms and other large molecules

into the cells. There are 2 types of endocytosis:

 Bulk-phase (nonspecific)

 Receptor-mediated (specific)

Peris Moraa Mokua

Process of Endocytosis

o The Plasma membrane surrounds material

o Edges of membrane meet

o Membranes fuse to form vesicle

Forms of endocytosis: Phagocytosis – cell eating

Pinocytosis – cell drinking

Fig. 13: Process of endocytosis

b) Exocytosis

Is the reverse of endocytosis whereby the cell discharges the material.

 Vesicle moves to cell surface

 Membrane of vesicle fuses

 Materials expelled

Fig. 14: Process of exocytosis

Peris Moraa Mokua

CELL DIVISION

Is the process by which a parent cell divides into two or more daughter cells. It usually occurs

as part of a larger cell cycle (Sequence of events that occurs between one cell division and the

next). The cell cycle has 3 stages:

1. Interphase: Cells grow and replicate their DNA

2. Nuclear division: Separation of chromatids

3. Cytokinesis: Division of cytoplasm and organelles

Fig. 15: Stages of cell cycle

Cell division differs in prokaryotes and eukaryotes. Prokaryotes such as bacteria undergo a

vegetative cell division known as binary fission, where their genetic material is segregated

equally into two identical daughter cells; a single chromosome makes a copy of itself and the

cell wall forms between the chromosomes dividing the cell. All cell divisions, regardless of

organism, are preceded by a single round of DNA replication. For simple unicellular

organisms such as the amoeba, one cell division is equivalent to reproduction – an entire new

organism is created.

In eukaryotes, cell division starts with division of the nucleus which occurs in two distinct

types of cell division: a vegetative division, whereby each daughter cell is genetically

identical to the parent cell (mitosis) and a reproductive cell division, whereby the number of

chromosomes in the daughter cells is reduced by half to produce haploid gametes (meiosis).

Meiosis results in four haploid daughter cells by undergoing one round of DNA replication

followed by two divisions. Replication is the process of duplicating a chromosome.

Homologous chromosomes are separated in the first division, and sister chromatids are

separated in the second division. Both of these cell division cycles are used in the process of

sexual reproduction at some point in their life cycle.

Importance of Cell division

 Maintenance of the original cell's genome. Before division can occur, the genomic

information that is stored in chromosomes must be replicated, and the duplicated

genome must be separated cleanly between cells.

 Growth

 Repair: worn-out or damaged cells

 Basis of reproduction

Peris Moraa Mokua

Phases of cell division

1. Interphase

Interphase is the process a cell must go through before mitosis, meiosis, and cytokinesis.

Interphase consists of four main stages: G1 (growth 1), S (synthesis phase), G2 (growth 2

phase), and M (Mitotic/meiotic phase). G1 is a time of growth for the cell. If the cell does not

progress through G1, the cell then enters a stage called G0 (resting phase). In G0, cells are

still living but they are put on hold. The cells may later be called back into interphase if

needed at a later time. There are checkpoints during interphase that allow the cell to be either

progressed or denied further development. In S phase, the chromosomes are replicated in

order for the genetic content to be maintained. During G2, the cell undergoes the final stages

of growth before it enters the M phase. The M phase, can be either mitosis or meiosis

depending on the type of cell. Germ cells undergo meiosis, while somatic cells will undergo

mitosis. After the cell proceeds through successfully through the M phase, it may then

undergo cell division through cytokinesis. The control of each checkpoint is controlled by

cyclin and cyclin dependent kinases. The progression of interphase is the result of the

increased amount of cyclin. As the amount of cyclin increases, more and more cyclin

dependent kinases attach to cyclin signaling the cell further into interphase. The peak of the

cyclin attached to the cyclin dependent kinases this system pushes the cell out of interphase

and into the M phase, where mitosis, meiosis, and cytokinesis occur.

Fig. 16: Interphase stage

2. Prophase

Prophase is the first stage of division. The nuclear envelope is broken down, long strands of

chromatin condense to form shorter more visible strands called chromosomes, the nucleolus

disappears, and microtubules attach to the chromosomes at the kinetochores present in the

centromere. Microtubules associated with the alignment and separation of chromosomes are

referred to as the spindle and spindle fibers. Chromosomes will also be visible under a

microscope and will be connected at the centromere. During this condensation and alignment

Peris Moraa Mokua

period, homologous chromosomes may swap portions of their DNA in a process known as

crossing over.

3. Metaphase

Chromosomes line up in the middle of the cell. The chromosomes are still condensing and are

currently at one step away from being the most coiled and condensed they will be. Spindle

and spindle fibers have already connected to the kinetochores. At this point, the

chromosomes are ready to split into opposite poles of the cell towards the spindle to which

they are connected.

4. Anaphase

Anaphase is a very short stage of the cell cycle and occurs after the chromosomes align at the

mitotic plate. After the chromosomes line up in the middle of the cell, the spindle fibers will

pull them apart. The chromosomes are split apart as the sister chromatids move to opposite

sides of the cell.

5. Telophase

Telophase is the last stage of the cell cycle. Two cells form around the chromatin at the two

poles of the cell. Two nuclear membranes begin to reform and the chromatin begin to

unwind.

Mitotic Cell Division

Mitosis is how somatic (non-reproductive) cells divide. Somatic cells make up most of your

body's tissues and organs, including skin, muscles, lungs, gut, and hair cells. In mitosis, the

important thing to remember is that the daughter cells each have the same chromosomes and

DNA as the parent cell. The daughter cells from mitosis are called diploid cells. Diploid cells

have two complete sets of chromosomes. Since the daughter cells have exact copies of their

parent cell's DNA, no genetic diversity is created through mitosis in normal healthy cells.

Fig. 17: Mitotic cell division

In mitotic cell division, the nucleus divides once creates two genetically identical daughter

diploid cells. The major steps of mitosis are shown here.

The Mitosis Cell Cycle

Before a cell starts dividing, it is in the "Interphase." Cells must be constantly dividing but

each cell spends most of its time in the interphase. Interphase is the period when a cell is

getting ready to divide and start the cell cycle. During this time, cells are gathering nutrients

Peris Moraa Mokua

and energy. The parent cell is also making a copy of its DNA to share equally between the

two daughter cells.

The mitosis division process has several steps or phases of the cell cycle—interphase,

prophase, prometaphase, metaphase, anaphase, telophase, and cytokinesis—to successfully

make the new diploid cells.

Fig. 18: Mitotic stages

When a cell divides during mitosis, some organelles are divided between the two daughter

cells. For example, mitochondria are capable of growing and dividing during the interphase,

so the daughter cells each have enough mitochondria. The Golgi apparatus, however, breaks

down before mitosis and reassembles in each of the new daughter cells.

Significance of mitosis

 Formation of new cells for growth

 Asexual reproduction

 Repair of worn-out or damaged cells

Meiosis Cell Division

Meiosis is cell division that creates sex cells, like female egg cells or male sperm cells. In

meiosis, each new cell contains a unique set of genetic information. After meiosis, the sperm

and egg cells can join to create a new organism. Meiosis is why we have genetic diversity

in all sexually reproducing organisms. During meiosis, a small portion of each chromosome

breaks off and reattaches to another chromosome. This process is called "crossing over" or

Peris Moraa Mokua

"genetic recombination." Genetic recombination is the reason full siblings made from egg

and sperm cells from the same two parents can look very different from one another.

The meiotic stage has 2 main stages of division: Meiosis I and II. The end product is four

haploid daughter cells each having different genetic information from each other and the

parent cell

Fig. 19: Meiotic cell division

The Meiosis Cell Cycle

Meiosis has two cycles of cell division, called Meiosis I and Meiosis II. Meiosis I halves the

number of chromosomes and is also when crossing over happens. Meiosis II halves the

amount of genetic information in each chromosome of each cell. The end result is four

daughter cells called haploid cells. Haploid cells only have one set of chromosomes - half the

number of chromosomes as the parent cell.

Before meiosis I starts, the cell goes through interphase. Just like in mitosis, the parent cell

uses this time to prepare for cell division by gathering nutrients and energy and making a

copy of its DNA. During the next stages of meiosis, this DNA will be switched around during

genetic recombination Interphase is divided into three phases:

 Growth 1 (G1) phase: Is a very active phase, the cell synthesizes its vast array of

proteins, including the enzymes and structural proteins it will need for growth. In G1,

each of the chromosomes consists of a single linear molecule of DNA.

 Synthesis (S) phase: The genetic material is replicated; each of the cell's

chromosomes duplicates to become two identical sister chromatids attached at a

centromere. This replication does not change the ploidy of the cell since the

centromere number remains the same. The identical sister chromatids have not yet

condensed into the densely packaged chromosomes visible with the light microscope.

This will take place during prophase I in meiosis.

 Growth 2 (G2) phase: G2 phase as seen before mitosis is not present in meiosis.

Meiotic prophase corresponds most closely to the G2 phase of the mitotic cell cycle.

Peris Moraa Mokua

Interphase is followed by meiosis I and then meiosis II. Meiosis I separates homologous

chromosomes, each still made up of two sister chromatids, into two daughter cells, thus

reducing the chromosome number by half. During meiosis II, sister chromatids decouple and

the resultant daughter chromosomes are segregated into four daughter cells. For diploid

organisms, the daughter cells resulting from meiosis are haploid and contain only one copy of

each chromosome. In some species, cells enter a resting phase known as interkinesis

between meiosis I and meiosis II.

Meiosis I and II are each divided into prophase, metaphase, anaphase, and telophase stages,

similar in purpose to their analogous sub phases in the mitotic cell cycle.

Phases

Fig. 20: Phases of meiosis cell division

Meiosis I

Meiosis I segregates homologous chromosomes, which are joined as tetrads (2n, 4c),

producing two haploid cells (n chromosomes, 23 in humans) which each contain chromatid

pairs (1n, 2c). Because the ploidy is reduced from diploid to haploid, meiosis I is referred to

as a reductional division.

Prophase I

Is typically the longest phase of meiosis. During prophase I, homologous chromosomes pair

and exchange DNA (homologous recombination). This often results in chromosomal

crossover. This process is critical for pairing between homologous chromosomes and hence

for accurate segregation of the chromosomes at the first meiosis division. The new

combinations of DNA created during crossover are a significant source of genetic variation,

and result in new combinations of alleles, which may be beneficial. The paired and replicated

chromosomes are called bivalents or tetrads, which have two chromosomes and four

chromatids, with one chromosome coming from each parent. The process of pairing the

homologous chromosomes is called synapsis. At this stage, non-sister chromatids may cross-

Peris Moraa Mokua

over at points called chiasmata. Prophase I is divided into a series of sub stages named

according to the appearance of chromosomes.

a) Leptotene

The first stage of prophase I, also known as leptonema (thin threads). In this stage, individual

chromosomes, each consisting of two sister chromatids, become "individualized" to form

visible strands within the nucleus. The two sister chromatids closely associate and are

visually indistinguishable from one another. During leptotene, lateral elements of the

synaptonemal complex assemble. Leptotene is of very short duration and progressive

condensation and coiling of chromosome fibers takes place.

b) Zygotene

The zygotene stage is also known as zygonema (paired threads) occurs as the chromosomes

approximately line up with each other into homologous chromosome pairs. The telomeres

cluster at one end of the nucleus. At this stage, the synapsis (pairing/coming together) of

homologous chromosomes takes place, facilitated by assembly of central element of the

synaptonemal complex. Pairing is brought about in a zipper-like fashion and may start at the

centromere (procentric), at the chromosome ends (proterminal), or at any other portion

(intermediate). Individuals of a pair are equal in length and in position of the centromere.

Thus pairing is highly specific and exact. The paired chromosomes are called bivalent or

tetrad chromosomes.

c) Pachytene

The pachytene stage, also known as pachynema (thick thread). At this point a tetrad of the

chromosomes has formed known as a bivalent. This is the stage when homologous

recombination, including chromosomal crossover (crossing over), occurs. Non-sister

chromatids of homologous chromosomes may exchange segments over regions of homology.

Sex chromosomes, however, are not wholly identical, and only exchange information over a

small region of homology. At the sites where exchange happens, chiasmata form. The

exchange of information between the non-sister chromatids results in a recombination of

information; each chromosome has the complete set of information it had before, and there

are no gaps formed as a result of the process. Because the chromosomes cannot be

distinguished in the synaptonemal complex, the actual act of crossing over is not perceivable

through the microscope, and chiasmata are not visible until the next stage.

d) Diplotene

During the diplotene stage, also known as diplonema (two threads) the synaptonemal

complex degrades and homologous chromosomes separate from one another a little. The

chromosomes themselves uncoil a bit, allowing some transcription of DNA. However, the

homologous chromosomes of each bivalent remain tightly bound at chiasmata, the regions

where crossing-over occurred. The chiasmata remain on the chromosomes until they are

severed at the transition to anaphase I.

In mammalian and human fetal oogenesis all developing oocytes develop to this stage and are

arrested before birth. This suspended state is referred to as the dictyotene stage or dictyate.

It lasts until meiosis is resumed to prepare the oocyte for ovulation, which happens at puberty

or even later.

Peris Moraa Mokua

e) Diakinesis

Chromosomes condense further during the diakinesis (moving through) stage. This is the first

point in meiosis where the four parts of the tetrads are actually visible. Sites of crossing over

entangle together, effectively overlapping, making chiasmata clearly visible. Other than this

observation, the rest of the stage closely resembles prometaphase of mitosis; the nucleoli

disappear, the nuclear membrane disintegrates into vesicles, and the meiotic spindles begins

to form.

Metaphase I

Homologous pairs of chromosomes move together and align along the equator of the

cell/metaphase plate: As kinetochore microtubules from both centrosomes attach to their

respective kinetochores, the paired homologous chromosomes align along an equatorial plane

that bisects the spindle, due to continuous counterbalancing forces exerted on the bivalents by

the microtubules emanating from the two kinetochores of homologous chromosomes. This

attachment is referred to as a bipolar attachment. The protein complex cohesin holds sister

chromatids together from the time of their replication until anaphase. In mitosis, the force of

kinetochore microtubules pulling in opposite directions creates tension. The cell senses this

tension and does not progress with anaphase until all the chromosomes are properly bi-

oriented. In meiosis, establishing tension requires at least one crossover per chromosome pair

in addition to cohesin between sister chromatids.

Anaphase I

Kinetochore microtubules shorten, pulling homologous chromosomes (which consist of a pair

of sister chromatids) to opposite poles. Non-kinetochore microtubules lengthen, pushing the

centrosomes farther apart. The cell elongates in preparation for division down the center.

Unlike in mitosis, only the cohesin from the chromosome arms is degraded while the cohesin

surrounding the centromere remains protected. This allows the sister chromatids to remain

attached together at their centromeres while homologs are segregated.

Telophase I

The first meiotic division effectively ends when the chromosomes arrive at the poles. Each

daughter cell now has half the number of chromosomes but each chromosome consists of a

pair of chromatids. The microtubules that make up the spindle network disappear, and a new

nuclear membrane surrounds each haploid set i.e. the nuclear envelope reassemble. The

chromosomes uncoil back into chromatin. Cytokinesis, the pinching of the cell membrane in

animal cells or the formation of the cell wall in plant cells, occurs, dividing the cell into two

thus completing the creation of two daughter cells. Sister chromatids remain attached during

telophase I.

Cells may enter a period of rest known as interkinesis or interphase II. No DNA

replication occurs during this stage.

Meiosis II

Meiosis II is an equational division analogous to mitosis, in which the sister chromatids are

segregated, creating four haploid daughter cells (1n, 1c). The four main steps of Meiosis II

are: Prophase II, Metaphase II, Anaphase II, and Telophase II.

Prophase II

Peris Moraa Mokua

Disappearance of the nucleoli and the nuclear envelope. Shortening and thickening of the

chromatids. Centrosomes move to the polar-regions and arrange spindle fibers for the second

meiotic division.

Metaphase II

The centromeres contain two kinetochores that attach to spindle fibers from the centrosomes

at opposite poles. Chromosomes align along equator of cell.

Anaphase II

The remaining centromeric cohesin is cleaved allowing the sister chromatids to separate. The

sister chromatids by convention are now called sister chromosomes as they move toward

opposing poles.

Telophase II

Last stage of meiotic division which is similar to telophase I, and is marked by

decondensation and lengthening of the chromosomes and the disassembly/disappearance of

the spindle. Nuclear envelopes reform/assemble and cytokinesis (cleavage or cell plate

formation) divides the cell into two eventually producing a total of four daughter cells, each

with a haploid set of chromosomes. Meiosis is now complete and ends up with four new

daughter cells and n divided between four haploid cells.

Importance of Meiosis

 It is the fundamental basis of sexual reproduction; It produces gametes (eggs &

sperms)

 Two haploid (1n) gametes are brought together through fertilization to form a diploid

(2n) zygote

Results of Meiosis

 Gametes (egg & sperm) form

 Four haploid cells with one copy of each chromosome

 One allele of each gene

 Different combinations of alleles for different genes along the chromosome

Table 3: Comparison of Meiosis and Mitosis

Meiosis

Mitosis

End result

Normally four cells, each with half

the number of chromosomes as the

parent

Two cells, having the same

number of chromosomes as

the parent

Function

Production of gametes (sex cells) in

sexually reproducing eukaryotes

Cellular reproduction, growth,

repair, asexual reproduction

Where does it

happen?

Germ cells; Reproductive cells of

almost all eukaryotes (animals,

plants, fungi, and protists)

Somatic cells; All

proliferating cells in all

eukaryotes except brain cells

Chromosome

number

Half of parent

Same as parent

Peris Moraa Mokua

When

At sexual maturity

Throughout life

Number of divisions

Genetically same as

parent?

Yes

Crossing over

happens?

Yes, normally occurs between each

pair of homologous chromosomes

Very rarely

Pairing of

homologous

chromosomes?

Yes

Cytokinesis

Occurs in Telophase I and Telophase

Occurs in Telophase

Centromeres split

Does not occur in Anaphase I, but

occurs in Anaphase II

Occurs in Anaphase

Regulation of the Cell Cycle

A eukaryotic cell cannot divide into two, the two into four, etc. unless two processes

alternate:

• Doubling of its genome (DNA) in S phase

(synthesis phase) of the cell cycle;

• Halving of that genome during mitosis (M phase).

The period between M and S is called G1; that between S and M is G2.

Fig. 21: The Cell Cycle

The cell cycle consists of 3 main stages:

• G1 phase- Growth and preparation of the chromosomes for replication. Cells

grow in size. There is active metabolic activities.

• S phase- Synthesis of DNA (and centrosomes) i.e. DNA replication.

Peris Moraa Mokua

• M phase- Mitosis (nuclear division), Cytokinesis (cytoplasmic division).

When a cell is in any phase of the cell cycle other than mitosis, it is often said to be in

interphase.

Fig. 21: Cell cycle stages

Steps in the cycle

• A rising level of G1-cyclins bind to their Cyclin dependent kinases (Cdks) and signal

the cell to prepare the chromosomes for replication.

• A rising level of S-phase promoting factor (SPF) — which includes cyclin A bound to

Cdk2 — enters the nucleus and prepares the cell to duplicate its DNA (and its

centrosomes).

• As DNA replication continues, cyclin E is destroyed, and the level of mitotic cyclins

begins to rise (in G2).

• M-phase promoting factor (the complex of mitotic cyclins with the M-phase Cdk)

initiates;

 Assembly of the mitotic spindle

 Breakdown of the nuclear envelope

 Condensation of the chromosomes

• These events take the cell to metaphase of mitosis.

• At this point, the M-phase promoting factor activates the anaphase-promoting

complex/cyclosome (APC/C) which;

 Allows the sister chromatids at the metaphase plate to separate

and move to the poles (= anaphase), completing mitosis.

 Destroys cyclin B. It does this by attaching it to the protein ubiquitin which targets it

for destruction by proteasomes.

 Turns on synthesis of G1 cyclin for the next turn of the cycle.

 Degrades geminin, a protein that has kept the freshly-synthesized DNA in S phase

from being re-replicated before mitosis. This is only one mechanism by which the

Peris Moraa Mokua

cell ensures that every portion of its genome is copied once — and only once —

during S phase.

Quality control of the cell cycle

Cell cycle checkpoints

A checkpoint is a stage in the eukaryotic cell cycle at which the cell examines internal (e.g.

DNA damage) and external (e.g. molecular signals) cues and "decides" whether or not to

move forward with division. The cell has several systems (checkpoints) for interrupting the

cell cycle if something goes wrong.

1. A check on completion of S phase/G1 checkpoint. Transition of S. The cell seems to

monitor the presence of the Okazaki fragments on the lagging strand during DNA replication.

The cell is not permitted to proceed in the cell cycle until these have disappeared. Checks for

cell size, nutrients, growth factors and DNA damage.

2. DNA damage checkpoints/G2 checkpoints. Transition of M. Checks for DNA damage

and completeness of DNA replication. These sense DNA damage caused by e.g. UV radiation

from the sun. p53, a famous tumor suppressor protein called guardian of genome is the first

line of DNA damage response. It acts in the following ways;

a). Stops cell cycle at the G1 checkpoints by triggering production of Cdk inhibitor proteins-

bind to Cdk-cyclin complex and block their activity buying time for DNA repair.

b). Activate DNA repair enzymes.

c). Trigger programmed cell death so damaged DNA is not passed on. This prevents

mutations;

 Before the cell enters S phase (a G1 checkpoint)

 During S phase

 After DNA replication (a G2 checkpoint).

3. Spindle checkpoints/M checkpoint. Transition of metaphase to anaphase. The cell

examines whether all the sister chromatids are correctly attached to the spindle microtubules.

Because the separation of the sister chromatids during anaphase is an irreversible step, the

cycle will not proceed until all the chromosomes are firmly attached to at least two spindle

fibers from opposite poles of the cell.

How this checkpoint work: Cells don't actually scan the metaphase plate to confirm that all of

the chromosomes are there. Instead, they look for "straggler" chromosomes that are in the

wrong place (e.g., floating around in the cytoplasm). If a chromosome is misplaced, the cell

will pause mitosis, allowing time for the spindle to capture the stray chromosome.

Some of these have been discovered to;

 Detect any failure of spindle fibers to attach to kinetochores and arrest the cell in

metaphase (M checkpoint);

 Detect improper alignment of the spindle itself and block cytokinesis;

 Trigger apoptosis if the damage is irreparable.

All the checkpoints examined require the services of a complex of proteins. Mutations in the

genes encoding some of these have been associated with cancer; that is, they are oncogenes.

This should not be surprising since checkpoint failures allow the cell to continue dividing

despite damage to its integrity.

Peris Moraa Mokua

Fig.22: Cell cycle check-points

Control of the Cell Cycle: Cell cycle regulators

The core control system of the cell cycle are proteins in the cytoplasm which include the

Cyclins, Cyclin-dependent kinases (Cdks), Maturation-Promoting Factor (MPF) and the

Anaphase Promoting Complex/Cyclosome (APC/C). They cause key events such as DNA

replication or chromosome separation to take place. They also make sure the cell cycle events

take place in the right order and that one phase for example G1 triggers the onset of the next

phase such as the S phase.

a). Cyclins

Are the most important core cell cycle regulator. They are a group of related proteins. Are of

various types;

 G1 cyclin (cyclin D)

 G1/S cyclins

 S-phase cyclins (cyclins E and A)

 Mitotic (M) cyclins (cyclins B and A)

Each cyclin is associated with a particular phase, transition or sets of phases in the cell cycle

and helps drive the events of that phase or period. For example, M cyclin promotes events of

M phase such as nuclear envelope breakdown and chromosome condensation. The levels of

the different cyclins vary considerably (rise and fall) across the cell cycle. A typical cyclin is

present at low levels for most of the cycle but increases strongly at the stage where it is

needed. G1 cyclins are unusual in that they are needed for much of the cell cycle.

b). Cyclin-dependent kinases (Cdks)

These are enzymes which phosphorylate (attach phosphate groups to) specific target proteins.

They work together with the cyclins. Alone Cdks are inactive but the binding of a cyclin

activates it making it a functional enzyme and allowing it to modify target proteins. The

attached phopsphate group acts like a switch making the target protein more or less active.

There are three types of Cdks:

Peris Moraa Mokua

 G1 Cdk (Cdk4)

 S-phase Cdk (Cdk2)

 M-phase Cdk (Cdk1)

Their levels in the cell remain fairly stable/constant across the cell cyle but Cdk activity and

target proteins change as levels of their various cyclins rise and fall., but each must bind the

appropriate cyclin (whose levels fluctuate) in order to be activated. They add phosphate

groups to a variety of protein substrates that control processes in the cell cycle.

When a cyclin attaches to a Cdk, it has 2 effects;

 It activates the Cdk as a kinase,

 It directs the Cdk to a specific set of target proteins, ones appropriate to the cell cycle

period controlled by the cyclin. For example, G1/S cyclins sends Ckds to s phase targets

(e. g promoting DNA replication) while the M cyclins send C.dks to M phase targets (e. g

making the nuclear membrane breakdown).

c). Maturation-promoting factor (MPF)

Is a Cdk bound to its M cyclin partner. Like a typical cyclin, M cyclin stays at low levels for

much of the cell cycle but builds up as the cell approaches the G2/M transition. As M cyclin

accumulates it binds to Cdks already present in the cell forming complexes posed to trigger

M phase. Once these complexes receive an additional signal (cell’s DNA is intact) they

become active and set the events of M phase in motion. The MPF complexes add phosphate

tags to several different proteins in the nuclear envelope resulting in its breakdown (key event

of early M phase) and also activates targets that promote chromosome condensation and other

M phase events.

d). The Anaphase-Promoting Complex/Cyclosome (APC/C)

The APC is also called the cyclosome, and the protein complex is often designated as the

APC/C. Is activated by the MPF. Causes M cyclins to be destroyed starting in anaphase. This

pushes the cell out of mitosis allowing the daughter cells to enter G1. It also causes

destruction of the proteins that hold sister chromatids together allowing them to separate in

anaphase and move to opposite poles of the cell.

The APC/C adds a small protein tag called ubiquitin (Ub).When a target is tagged with Ub it

is sent to proteasome (recycle bin of the cell) and destroyed. E.g. the APC attaches a UB tag

to M cyclins causing them to be chopped up by the proteasome and allowing the newly

forming daughter cells to enter G1 phase. It also uses Ub tagging to trigger the separation of

sister chromatids during mitosis. If it gets the rights signals at metaphase, it sets off a chain fo

events that destroys cohesion (a protein holding sster chromatids together); The APC first

adds a Ub tag to a protein called securing sending it for recycling. Securing normally binds to

and inactivates a protein called separase. When securing is sent for recycling, separase

becomes active, it chops up the cohesin that holds sister chromatids together allowing them to

separate.

 Triggers the events leading to destruction of the cohesins thus allowing the sister

chromatids to separate;

 Degrades the mitotic cyclin B.

Students also viewed