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2018-2019

MEDICAL BIOLOGY CYTOLOGY

LECTURER: FARAH E. ISMAEEL

Prepared by: Farah E. Ismaeel & Dr. Mohammed H. Assi Reference: Junqueiras Basic Histology Text and Atlas 13th &

Mader Human Biology, 12th edition

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Biology is the science that studies all living things and their environments, all living

thing called living organisms. Biologist classify the living organism according to the present of nucleus to

eukaryotic organism include (animals, plants, protozoa, fungi) and prokaryotic

organism include (bacteria and some type of blue alge). Also classify according to the

number of the cell to unicellular organism and multicellular organism.

All living organisms share common characteristics:

1. acquire materials and energy from the environment

2. reproduce and develop

3. maintain homeostasis

4. respond to stimuli

5. Have an evolutionary history and are adapted to a way of life.

Human is eukaryotic organism from animal kingdom and have the same characters

of all living organism and have levels of organization. Figure 1.illustrates that atoms

join together to form the molecules that make up a cell. A cell is the smallest

structural and functional unit of an organism. Humans are multicellular because they

are composed of many different types of cells. A nerve cell is one of the types of cells

in the human body. It has a structure suitable to conducting a nerve impulse.

A tissue is a group of similar cells that perform a particular function. Nervous tissue

is composed of millions of nerve cells that transmit signals to all parts of the body.

Several types of tissues make up an organ, and each organ belongs to an organ

system. The organs of an organ system are work together to accomplish a common

purpose.

The brain works with the spinal cord to send commands to body parts by way of

nerves. Organisms, such as humans, are a collection of organ systems.

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Figure1: level of human organization

Human biology is a branch of biology concerned with the development and

functioning of the human organism and aspects of the life of human populations such

as their ecology, genetics, and epidemiology.

Medical biology is a field of human biology that has practical applications

in medicine, health care and laboratory diagnostics. It includes

many biomedical disciplines and areas of specialty that typically contain the "bio

"prefix such as: molecular biology, biochemistry, biophysics, biotechnology, cell

biology , laboratory medical biology, biostatistics, microbiology and many others that

generally concern life sciences as applied to medicine.

The first level of organization to the human is the cell.

Cell is a smallest basic structural and functional unit of all living organisms that

maintain proper homeostasis of the body.

Most cells are small and can be seen only under a microscope. The small size of

cells means that they are measured using the smaller units of the metric system, such

as the micrometer (μm). A micrometer is 1/1,000 millimeter. The micrometer is the

common unit of measurement for people who use microscopes professionally. Most

human cells are about 100μm in diameter, about the width of a human hair. The

internal contents of a cell are even smaller and, in most cases, may only be viewed

using powerful microscopes (Electron microscope). The science that studies the

microscopic appearance of cells is known as cytology.

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Figure2: eukaryotic cell structure

Internal Structure of human Cells

Certain structural feature common to all human cells but there are some different

between cells according to cell type and cell function.figure2

In general the basic human cell components are:

1. Plasma membrane (plasmalemma).

2. Cytoplasm: that include cytosol, cell organelles and inclusions

3. Nucleus.

Plasma membrane

A human cell, like all cells, is surrounded by an outer membrane called plasma

membrane or plasmalemma is a thin semi permeable membrane, composed from

lipid and protein that surrounded cytoplasm of a cell and control the passage of

substance into and out of the cell. The integrity and function of the plasma membrane

are necessary to the life of the cell.

Membranes range from 7.5 to 10 nm in thickness and consequently are visible only

With the transmission electron microscope (TEM) the cell membrane—and all other

organelles membranes—may exhibit a tri-laminar appearance after fixation in

osmium tetroxide; osmium binding the polar heads of the phospholipids, the outer

sugar chains, and associated membrane proteins produces the two dark outer lines

enclosing the light band of osmium-free fatty acids three layers, two dark layers

separated by light one.Figure3

Figure3: cell membrane can stain as two dark layers plus one clear layer from the gap between them,

similar to two stacked bread sandwiches with space between them

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The line between adjacent cells sometimes seen faintly with the light microscope

is formed by plasma membrane proteins plus extracellular material, which together

can reach a dimension visible by light microscopy.

The plasma membrane is a phospholipid bilayer (fluid at body temperature) with

attached or embedded proteins. The proteins are able to change their position by

moving laterally, the fluid-mosaic model is a working description of membrane

structure. It states that the protein molecules form a shifting pattern within the fluid

phospholipid bilayer. (See Figure 4).

Figure4: Organization of the plasma membrane.

Chemical structure of plasma membrane

1. Membrane lipids: lipid constitutes 30% of the mass of most cell membranes,

although this proportion varies depending on the type of cell. Include

phospholipids and cholesterol.

i. Phospholipids: The fundamental building blocks of all cell membranes, which are

amphipathic molecules, consisting of two hydrophobic fatty acid chains linked to

a phosphate- containing hydrophilic head group.

A. The hydrophilic (polar) heads of the phospholipids molecules face the

intercellular and extracellular fluids.

B. The hydrophobic (non polar) tail face each other in the membrane

interior.

When phospholipids are placed in water, they naturally form a spherical bilayer.

The polar heads, being charged, are hydrophilic (attracted to water). They position

themselves to face toward the watery environment outside and inside the cell. The

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nonpolar tails are hydrophobic (not attracted to water). They turn inward toward

one another, where there is no water.

At body temperature (37C), the phospholipid bilayer of the plasma membrane has

the consistency of olive oil. The entire phospholipids molecules can move side

away, all these means that the cell is pliable.

ii. Cholesterol:

Cholesterol is reduces the permeability of the membrane to the most biological

molecules. Have important role in Stability of cell membrane and make it more rigid.

Regulate the fluidity of phospholipids bilayer.

Ratio of phospholipid to cholesterol is 1:1

2. Membrane proteins: proteins constituting 50% of the mass of various

membranes of the cells. Membrane proteins carry out the specific functions of the

different membranes of the cell. These proteins are divided into two general

classes, based on the nature of their association with the membrane:

i. Integral membrane proteins: are large protein molecules and embedded

directly within the lipid bilayer, many integral membrane proteins called

transmembrane proteins span the lipid bilayer with proteins exposed on both

sides of the membrane (closely attached protein).

ii. Peripheral membrane proteins: are small protein molecules and not inserted

into the lipid bilayer but are associated with the membrane indirectly, generally

by interactions with integral membrane proteins (loosely attached).

3. Membrane glycolipids and glycoprotiens;

Short chains of sugars (oligosaccride) are attached to the outer surface of some

protein and lipid molecules. The carbohydrate chains of glycolipids and glycoproteins

are serving as the fingerprints of the cell. These carbohydrate chains, specific to each

cell, help mark the cell as belonging to a particular individual. They account for why

people have different blood types, for example.

The carbohydrate chains of the glycolipids & glycoproteins form a carbohydrate coat

that envelops the outer surface of the plasma membrane.

On the inside, proteins serve as links to the cytoskeletal filaments and on the outside

some serve as links to extracellular matrix.

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i. Glycolipids:

Have a structure similar to phospholipids except that the hydrophilic head is a

variety of sugars joined to form a straight or branching carbohydrate chain.

Glycolipids have a protective function.

ii. Glycoprotein (glycocalyx)

Is delicate fuzzy cell coat

Composed of carbohydrate molecules that are attached to the integral proteins

of the cell membrane and project from the external cell surface.

Have an important role in cell recognition, cell to cell attachment or adhesions

and act as receptor for chemical messenger or binding sites for different

protein hormones.

Cell coat present on special type of cell and don’t present on others make

some cell effect with virus, bacteria, hormones and drugs.

Why the HBV infect only liver cells and don’t infect other cells?

Cell membrane transport, specializations and functions

Cell membrane or plasma membrane is selectively permeable membrane also

regarded as differentially permeable membrane or semi permeable membrane,

because is allow some molecules pass through it while prevent other molecule from

passing.

Permeable molecules to the cell membrane include: small hydrophobic molecule like

O2, CO2, N2 and benzene. And small uncharged polar molecules like water, glycerol

and ethanol.

Non permeable molecules to the cell membrane include: large uncharged polar

molecules like sugar, amino acids. And Ions like H+, Na+, K+, Cl¯, Ca++, Mg++,

HCO3¯.

Molecules cross the plasma membrane in 2 ways:

1. Passive ways: no energy used. Include: simple diffusion, channel diffusion and

facilitated diffusion.

2. Active ways: use energy. Include: active transport, endocytosis & exocytosis.

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Passive ways

1. Simple diffusion is the movement of molecules from higher concentration to

lower concentration until they are distributed equally for examples

o Gases diffuse through the lipid bilayer, this is the mechanism by which

oxygen enters cells and carbon dioxide exits cells

o Glycerol and ethanol diffuse simply through the plasma membrane.

o Water also can diffuse through the plasma membrane by using protein

channels called aquaporins. This phenomenon called osmosis.

Figure5A: cell membrane permeability, simple diffusion (osmosis)

Osmosis is the movement of water molecules through semi-permeable

membrane from a solution with a low solute concentration to a solution with a

higher solute concentration until there is an equal solute concentration on both

sides of the membrane.

Osmotic pressure refers to the amount of pressure that necessary to stop the flow of

water across the semi permeable membrane and is developed on the side of the

membrane that has the higher solute concentration

Solution is a homogeneous mixture of one or more substances

(Solutes) dispersed molecules in a sufficient quantity of dissolving medium (solvent).

e.g. on solvent distilled water and solutes sugar or salts.

Isotonic solution

Isotonic solution refers to two solutions having the same osmotic pressure

across a semi permeable membrane

Solution that causes cells neither to gain nor to lose water that is the solute

concentration is the same on both sides of the membrane.

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Normal saline solution is the most common example on isotonic solution, is

containing 0.9% of sodium chloride (NaCl) is known to be isotonic to red

blood cells because the cells neither swell nor shrink when placed in other

solution.

Therefore, physician must put this point in his mind when giving fluid to the

patients that suffering from dehydration. Use isotonic solution as intravenous

fluid in medical settings.

Hypertonic solution:

Solutions that cause cells to shrink due to loss of water.

Any concentration with a concentration higher than 0.9% sodium chloride

is hypertonic to red blood cells.

E.g. concentrated salt solution

Hypotonic solution:

Solutions that cause cells to swell or even to burst, due to an intake of

water.

Any concentration of salt solution lower than 0.9% is hypotonic to red

blood cell E.g. distilled water.

Figure5B: Osmosis in human red blood cell (RBC)

3. Channel diffusion: this type of passive transport system also don’t use energy,

used for movement of Ions (H- or Cl-) required only channel protein.

4. Facilitated diffusion: is another type of passive transport system doesn’t use

energy but required a carrier protein assist the movement of glucose or amino

acids. Each protein carrier, sometimes called a transporter, binds only to a

particular molecule, such as glucose.

Type 2 diabetes mellitus results when cells lack a sufficient number of glucose

transporters.

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Active ways

1. Active transport: molecules and ions can be transported across cell membrane

against their concentration gradient if the appropriate transport proteins and a

source of energy (ATP) are available.

ATP Adenosine Triphosphate -Nucleotide with three phosphate groups.

The breakdown of ATP into ADP one phosphate molecules makes energy

available for energy-requiring processes in cells.

Proteins involved in active transport often are called pumps, just as a water

pump uses energy to move water against the force of gravity; energy is used to

move substances against their concentration gradients.

Sodium-Potassium Pump – is transport protein (pump) in the plasma membrane

that moves sodium ions (Na+) out of and potassium ions (K

+) into animal cells;

important in nerve and muscle cells. The sodium potassium pump cause an

electrical concentration gradient (difference of charge) across the membrane and

this is known as a membrane potential. Nerve cells use this membrane potential to

send electrical signals along nerves. The passage of salt (NaCl) across a plasma

membrane is of primary importance in cells. First, sodium ions are pumped across

a membrane. Then, chloride ions diffuse through channels that allow their

passage.

Figure6: Types of C.M. transport

One of important clinical application on active transport is a cystic fibrosis.

Cystic fibrosis is a genetic disorder occurs when there is a defects in a gene on chromosome 7

.This gene, called CFTR (cystic fibrosis Transmembrane conductance regulator), codes for the

CFTR protein is a channel protein that controls the flow of H2O and Cl- ions in and out of cells

inside the lungs. When the CFTR protein is working correctly, ions freely flow in and out of the

cells. However, when the CFTR protein is malfunctioning, these ions cannot flow out of the cell

due to a blocked channel. This causes cystic fibrosis, characterized by the buildup of thick

mucus in the lungs.

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2. Endocytosis: is uptake process of molecules and transport it across cell

membrane into the cell interior by vesicle formation, a portion of the plasma

membrane invaginates to envelop the substance, and then the membrane pinches

off to form an intracellular vesicle.

There are three methods of endocytosis:

A. Phagocytosis: means "cell eating", occurs when large solid materials taken inside

the cell, such as food particles, dead cell, cell debris or another cell such as

bacteria . Best example on phagocytic cell is white blood cells (WBC) can engulf

bacteria and worn- out red blood cells by phagocytosis. Digestion occurs when the

resulting vacuole (phagocytic vacuole) fuses with a lysosome.(figure7A.a)

B. Pinocytosis: means "cell drinking", occurs when vesicles form around fluid

droplets. e.g. cells that line the kidney tubules or intestinal wall use this method of

ingesting water substances. Also an inherited form of cardiovascular disease

occurs when cells fail to take up a combined lipoprotein and cholesterol molecule

from the blood by pinocytosis.(figure7A.b)

C. Receptor- mediated endocytosis: A special form of endocytosis uses a receptor,

a special form of membrane protein, on the surface of the cell to concentrate

specific molecules of interest for endocytosis. (figure7A.c)

Figure7A:

The

methods of

endocytosis

An inherited form of cardiovascular disease occurs when cells fail to take up a

combined lipoprotein and cholesterol molecule from the blood by receptor-

mediated endocytosis.

Also one type of dwarfism are caused by nonfunctioning growth hormone

receptors, In this condition the gland produce the hormone, but the target cells

cannot respond because they lack normal receptors.

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3. Exocytosis: is release process of material from the cell. During exocytosis

vesicles often formed by Golgi apparatus and carrying a specific molecule fused

with plasma membrane and secretion occurs. e.g. release of insulin molecules

from beta cells or releasing of neurotransmitter molecules into the synaptic

cleft by the process of exocytosis. figure7B

Figure7B: The exocytosis of vesicles containing neurotransmitter molecules

Cell membrane specialization

The lateral parts of the cell membrane can show several specializations that form

"intercellular junctions", functions of these junctions:

1. Sites of adhesion between adjacent cells.

2. Prevent the flow of materials through the intercellular compartment.

3. Help in the intercellular communication.

The three main types of cell junctions in human cells is

1. Adhesion junctions serve to mechanically attach adjacent cells. In these junctions,

the cytoskeletons of two adjacent cells are interconnected. They are a common

type of junction between skin cells. (figure8.c)

2. Tight junctions, connections between the plasma membrane proteins of

neighboring cells produce a zipper like barrier. These types of junctions are

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common in the digestive system and the kidney, where it is necessary to contain

fluids (digestive juices and urine) within a specific area. (figure8.a)

3. Gap junctions serve as communication portals between cells. In these junctions,

channel proteins of the plasma membrane fuse, allowing easy movement between

adjacent cells.(figure8.b)

Figure8: shows Junctions between cells.

Functions of plasma membrane

1. Protect a cell by acting as a barrier between cell contents and surrounding

environment.

2. Regulate the movement of substances in and out of a cell. It allows the

passage of substance selectively in order to maintain a constant cell

environment a phenomenon called homeostasis.

3. Connect cells together in specific way by cell junctions and pass on

information to neighboring cell, so that the activities of tissue and organs are

coordinated.

4. Serve as the attachment surface for many extracellular structures.

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The Cytoplasm

The cytoplasm is the part of the cell located outside the nucleus full the space

between nuclear envelop and plasma membrane consists of

1. Cytosol is a larger fluid component.

2. Organelles (“little organs”) are bathing metabolically active structures, which

may be membranous (such as mitochondria) or non membranous protein

complexes (such as ribosomes and proteasomes).

3. Cytoskeleton is protein components which determine the shape and motility

of eukaryotic cells.

4. Inclusions are the minor cytoplasmic structures that are not usually

surrounded by a plasma membrane. They consist of such diverse materials as

crystals, pigment granules, lipids, glycogen, and other stored waste products.

Cytosol

Cytosol is an aqueous gel called the cytoplasmic matrix.

The matrix consists of a variety of solutes, including inorganic ions (Na, K, and

Ca2) and organic molecules such as intermediate metabolites, carbohydrates,

lipids, proteins, and RNAs. The cell controls the concentration of solutes within

the matrix, which influences the rate of metabolic activity within the cytoplasmic

compartment.

Cytosol also contains hundreds of enzymes, all the machinery converging on the

ribosomes for protein synthesis, Oxygen, CO2, electrolytic ions, low-molecular-

weight substrates, metabolites, and waste products all diffuse through cytosol,

either freely or bound to proteins, entering or leaving organelles where they are

used or produced.

Organelles

All cells have the same basic set of intracellular organelles, which can be

classified into two groups:

1. Membranous organelles with plasma membranes that separate the internal

environment of the organelle from the cytoplasm.

2. Non membranous organelles without plasma membranes.

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The membranes of membranous organelles form vesicular, tubular, and other

structural patterns within the cytoplasm that may be convoluted (as in smooth-

surfaced endoplasmic reticulum) or plicated (as in the inner mitochondrial

membrane).

In addition, each type of organelle contains a set of unique proteins.

o In membranous organelles, these proteins are either incorporated into their

membranes or sequestered within their lumens. For example, the enzymes of

lysosomes are separated by a specific enzyme resistant membrane from the

cytoplasmic matrix because their hydrolytic activity would be detrimental to

the cell.

o In Non membranous organelles, the unique proteins usually self assemble

into polymers that form the structural elements of the cytoskeleton.

Membrane bounded organelles

Endoplasmic reticulum (ER)

The largest organelle of most eukaryotic cells is ER.

ER is a network of intercommunicating channels and sacs formed by a

continuous membrane which encloses a space called cisternae this network

(reticulum) extends from the surface of the nucleus to the cell membrane.

The main function of ER is the transport of materials by forms transport

vesicles in which large molecules are transported to other parts of the cell.

Often, these vesicles are on their way to the plasma membrane or the Golgi

apparatus.

There are two types of ER according to the present of ribosome, Rough ER

and Smooth ER.

Figure 9: Transmission EM of RER&SER

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Rough ER (RER)

It's 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. Is found in all cells except erythrocytes and is especially

abundant in pancreas, fibroblasts and plasma cells.

Function of RER:

1. Has role in the synthesis of protein to be exported outside the cell.

2. Modification of newly formed polypeptides.

3. Assembly of multichain protein.

4. Initial glycosylation of the glycoprotein which means addition of glucose to

the protein.

RER has a highly regulated system to prevent nonfunctional proteins being

forwarded to the pathway for secretion or to other organelles. New proteins that

cannot be folded or assembled properly by chaperones undergo ER-associated

degradation (ERAD), in which unsalvageable proteins are translocated back into

the cytosol, conjugated to ubiquitin, and then degraded by proteasomes.

Smooth ER (SER)

Are continuous with rough ER, does not have attached ribosomes (figure 9).

Smooth ER synthesizes the phospholipids that occur in membranes and has

various other functions, depending on the particular cell.

1. SER in Testes is produce testosterone.

2. SER in liver is detoxified drugs, alcohol and toxin. Also have role in lipid

and cholesterol synthesis. And glycogen breakdown.

3. SER in adrenal glands is produces steroid hormones

Quality control during protein production in the RER and properly functioning ERAD to

dispose of defective proteins are extremely important and several inherited diseases

result from malfunctions in this system. For example, in some forms of osteogenesis

imperfect bone cells synthesize and secrete defective procollagen molecules which

cannot assemble properly and produce very weak bone tissue.

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4. SER in muscle cells has role in contraction process (SER in muscle cells

called sarcoplasmic reticulum).

5. SER Transport molecules to the Golgi body.

6. SER is metabolized lipid and cholesterol.

Golgi apparatus

Golgi apparatus is consists of a stack of slightly curved saccules with convex

side as the cis face and mature concave side is the trans face that separated

from ER.

Present in typical eukaryotic cells, highly developed in secretary cells.

In most cells, there is a polarity in the Golgi bodies.(most polar organelle)

Protein and lipid vesicle from ER fused with cis face of Golgi apparatus then

subsequently progress through the stack to trans face of Golgi apparatus that

contain cisternae enzyme. Cisternae enzyme modify, sort and package proteins

also add sugar to protein and lipid to form glycoproteins, glycolipids and

lipoproteins. These molecules packaged in membrane for export outside of

cell or for lysosomes.

Figure10: The Golgi apparatus

Jaundice denotes a yellowish discoloration of the skin and is caused by accumulation in

extracellular fluid of bilirubin and other pigmented compounds, which are normally

metabolized by SER enzymes in cells of the liver and excreted as bile. A frequent cause of

jaundice in newborn infants (physiological jaundice) is an under developed state of SER in

liver cells, with failure of bilirubin to be converted to a form that can be readily excreted.

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Lysosomes

Lysosomes are membrane bounded organelles that contain about 40 different

hydrolytic enzymes produced by the Golgi apparatus.

Lysosomal hydrolases are synthesized and segregated in the RER and then

transferred to the Golgi apparatus, where the enzymes are further modified and

packaged in vacuoles that form lysosomes.

Particularly abundant in cells with great phagocytic activity (eg, macrophages,

neutrophils) because it digest any foreign substance by hydrolytic enzyme.

Have important role in post mortum autolysis.

Maintain cell health by remove all old endogenous macromolecules.

Material taken from outside the cell by endocytosis is digested when the

membrane of the phagosome or pinocytotic vesicle fuses with a lysosome. The

composite, active organelle is now termed a secondary or heterolysosome.

Heterolysosomes are generally somewhat larger and have a more heterogeneous

appearance in the TEM because of the wide variety of materials they may be

digesting. During this digestion of macromolecules, released nutrients diffuse into

the cytosol through the lysosomal membrane. Indigestible material is retained

within a small vacuolar remnant called a residual body. In some long-lived cells

(eg, neurons, heart muscle), residual bodies can accumulate over time as granules

of lipofuscin.( Figure 19)

Besides degrading exogenous macromolecules, lysosomes also function in the

removal of excess or nonfunctional organelles and other cytoplasmic structures

(endogenous macromolecules) in a process called autophagy. A membrane from

SER forms around the organelle or cytoplasmic portion to be removed, producing

an autophagosome. These then fuse with lysosomes that digest the enclosed

cytoplasm. Autophagy is enhanced in secretory cells that have accumulated

excess secretory granules and in times of nutrient stress, such as starvation.

Digested products from autophagosomes are reused in the cytoplasm.

Diseases categorized as lysosomal storage disorders stem from defects in one or more

of the digestive enzymes present in lysosomes .

In cells that must digest the substrate of the missing or defective enzyme following

autophagocytosis, the lysosomes cannot function properly. Such cells accumulate

large secondary lysosomes or residual bodies filled with the indigestible

macromolecule. The accumulation of these vacuoles may eventually interfere with

normal cell or tissue function, producing symptoms of the disease.

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Figure11: Show the endogenous and exogenous digestion by lysosome

Mitochondria

Mitochondria (singular, mitochondrion) are membrane-bounded organelles

They are usually elongated structures.

They are highly plastic, rapidly changing shape, fusing with one another and

dividing, and are moved through the cytoplasm along microtubules.

The number of mitochondria is related to the cell’s energy needs: cells with a

high-energy metabolism (eg, cardiac muscle, liver cells and cells of some kidney

tubules) have abundant mitochondria, whereas cells with a low-energy

metabolism have few mitochondria such as small lymphocyte

Mitochondria are often called the powerhouses of the cell. Just as a powerhouse

burns fuel to produce electricity, the mitochondria convert the chemical energy

of glucose products into the chemical energy of ATP molecules. In the process,

mitochondria use up oxygen and give off carbon dioxide. Therefore, the process

of producing ATP is called cellular respiration.

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Figure 12: Mitochondrial structure

The structure of mitochondria: each mitochondrion consists of:

1. Outer membrane: is smooth membrane surrounded that allows entry of

molecules and contain enzyme involved in mitochondrial lipid synthesis.

2. Intermembrane space: Because of channels in the outer membrane of

the mitochondria, the content of the intermembrane space is similar to that of

the content of the cytoplasm.

3. Inner membrane: exhibit numerous folds called cristae which maximize

internal surface area of mitochondria and contain most of the respiratory chain

enzymes and ATP synthase which is responsible for cell respiration (oxidative

phosphorylation) and production of cell ATP. Shape of cristea different

according type of cells; in protein secreting cells cristea project into the interior

of the organelle like shelve. In steroid secreting cells such as the adrenal cortex

or interstitial cells in the testes, the mitochondria cristea are tubular.

4. Mitochondrial matrix: the matrix is the space within the inner membrane;

contain enzymes for Krebs cycle, mitochondrial DNA (circular DNA), special

ribosome, tRNase and enzymes for gene expression.

o Mitochondrial DNA is double stranded and has a circular structure very

similar to bacterial chromosomes, mitochondrial DNA synthesis and

duplication is independent of nuclear DNA replication.

o Mitochondrial ribosome is smaller than cytosolic ribosome.

o tRNases are enzymes that degraded the tRNA.

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The structure of a mitochondrion supports the hypothesis that they were originally

prokaryotes engulfed by a cell!

Mitochondria are bounded by a double membrane, as a prokaryote would be if

taken into a cell by endocytosis.

Even more interesting is the observation that mitochondria have their own

genes—and they reproduce themselves.

Replication of mitochondria

Mitochondria replicate similarly to bacterial cells, when they get large, they

undergo fission. This involves furrowing of the inner and then the outer

membrane as if someone was pinching the mitochondrion. The two daughter cells

of the mitochondria must first replicate the DNA.

Function of mitochondria

1. Mitochondria are primary sites for ATP synthesis (site of Krebs cycle) from

organic material so that known as powerhouse of the cell.

2. Cell respiration.

3. Maintain body heat because some energy dissipated as heat.

4. They have key role in apoptosis programmed cell death.

5. Some mitochondrial functions are performed only in specific types of cells, e.g.

mitochondria in liver cells contain enzymes that allow them to detoxify

ammonia, a waste product of protein metabolism.

(Why the mtDNA is inherited solely from the mother?)

Peroxisome

Small membrane bounded organelle. Present in all cell type.

Named for their enzymes producing and degrading hydrogen peroxide (H2O2),

which is potentially damaging to the cell.

Similar to lysosome but less dense and contain no hydrolytic enzyme but

contain several types of oxidases and catalases enzymes

A maternally-inherited mutation in the mitochondrial genome is leading to defective

synthesis of respiratory chain proteins which can produce structural abnormal in muscle

fibers especially skeletal muscle fibers are very sensitive to mitochondrial defect

(muscular dysfunction) and other cells. (This called mitochondrial disorders)

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o Oxidases is enzyme that oxidized various organic substance to form

hydrogen peroxide highly toxic product

o Catalase enzyme which eliminate excess hydrogen peroxide by breaking it

down into water and oxygen molecule. These enzymes also inactivate various

potentially toxic molecules, including some prescription drugs.

So that the peroxisome protect the cell from the cytotoxic product because the

degradation of hydrogen peroxide occur in the same organelle

Very abundant in the cell of liver and kidney.

Figure13: The structure of peroxisome under TEM

Peroxisomes form in two ways:

1. Budding of precursor vesicles from the ER

2. Or growth and division of preexisting peroxisomes.

These organelles lack nucleic acids; their enzymes are synthesized on free cytosolic

polyribosomes and bear a small signal sequence of amino acids at the carboxyl

terminus. This signal is recognized by receptors located in the peroxisomal membrane

and the proteins are imported.

Deficiencies of peroxisomal enzymes cause what is called peroxisomal disoreders (exp:

Zellweger syndrome) that affects the structure and functions of several organ systems,

producing symptoms of the disease.

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Non membrane bounded organelles

Ribosomes

Ribosomes are membrane naked organelles present in all cells types( prokaryotes and

eukaryotes)

Ribosomes are small electron-dense particles composed of proteins and rRNA.

All ribosomes have two subunits of different sizes and act to catalyze the process of

protein translation (Protein synthesis), so that is more abundant in protein secreting

cells.

In eukaryotic cells, the rRNA molecules of both subunits are synthesized within the

nucleus. Their numerous proteins are synthesized in the cytoplasm but then enter the

nucleus and associate with rRNAs. The assembled large and small subunits then leave

the nucleus and enter the cytoplasm to participate in protein synthesis.

Ribosomes are often attached to the endoplasmic reticulum; but they also may occur

free within the cytoplasm, either singly or in groups called polyribosomes or

polysomes.

Figure14: Ribosome (TEM image of and diagram)

Proteins synthesized at ribosomes attached to the endoplasmic reticulum have a different

destination from that of proteins manufactured at ribosomes free in the cytoplasm.

Attached ribosomes are synthesis any proteins that packaged or release from the cells as

secretary product, While free polyribosome synthesis protein that use within the cell such

as enzymes of peroxisome and enzymes of glycolysis.

Proteasomes

Proteasomes are very small abundant protein complexes composed of three

subunits : two regulatory particles and one core particle

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Non membranous organelle that degrades some protein molecules that attached

to Upiquitin protein by ATP dependent pathway.

They function to degrade excess enzyme, denatured or otherwise nonfunctional

polypeptides also remove proteins no longer needed by the cell and provide an

important mechanism for restricting activity of a specific protein to a certain

window of time. Destroy protein infected by viruses. Whereas lysosomes digest

organelles or membranes by autophagy, proteasomes deal primarily with free

proteins as individual molecules.

Figure15: Diagram of proteasome and Upiquitin pathway

The Cytoskeleton, Cell Movement, and Cytoplasmic inclusions

The Cytoskeleton is a network of tiny protein filaments and tubules that extend

throughout the cytoplasm. It serves the cell’s structural framework, helps maintain a

cell’s shape and either anchors the organelles or assists in the movements of

organelles and cytoplasmic vesicles, and also allows the movement of entire cells.

Figure16: Types of cytoskeletons

Failure of proteasomes or other aspects of a cell’s protein quality control can allow

large aggregates of protein to accumulate in affected cells. Such aggregates may adsorb

other macromolecules to them and damage or kill cells.

Aggregates released from dead cells can accumulate in the extracellular matrix of the

tissue. In the brain this can interfere directly with cell function and lead to

neurodegeneration.

Alzheimer disease and Huntington disease are two neurologic disorders caused initially

by such protein aggregates.

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Microtubules (MTs)

Microtubules are found in almost all eukaryotic cell types except red blood cells.

They are the largest elements of the cytoskeleton.

Microtubules are non branching and rigid hollow tubes of protein that can rapidly

disassemble in one location and reassemble in another.

All microtubules originate from the microtubule-organizing center (MTOC) called

centrosome, has gamma tubulin (γ).

Centrosome is an area of the cytoplasm located near the nucleus

Microtubules are elongated polymeric structures composed of equal parts of α

tubulin and β tubulin.

Microtubules grow from γ tubulin rings within the MTOC that serve as nucleation

sites for each microtubule.

The length of microtubules changes dynamically as tubulin dimers are added or

removed in a process of dynamic instability.

In the centrosome, the tubulin subunits polymerize and from two types of

microtubules:

Dynamic microtubules are continuous assembly and disassembly (reshaping of

cell) determine cell shape and function in intracellular movement of organelles

and secretory granules and form spindles that guide the movement of

chromosomes during cell division or mitosis

Stable microtubules form walls of centrioles, cilia and flagella. They are

responsible for the beating movements

Microtubules are involved in numerous essential cellular functions:

1. Intracellular vesicular transport (e.g., movement of secretory vesicles, endosomes,

and lysosomes).

2. Movement of cilia and flagella.

3. Attachment of chromosomes to the mitotic spindle and their movement during

mitosis and meiosis.

4. Cell elongation and movement (migration).

5. Maintenance of cell shape, particularly its asymmetry.

Several inhibitory compounds used by cell biologists to study details of

microtubule dynamics are also widely used in cancer chemotherapy to block

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activity of the mitotic spindle in rapidly growing neoplastic cells. Such drugs

include vinblastine and vincristine.

Centrioles:

Centrioles are non membranous organelles. Small cylindrical structures composed of

highly organized microtubules located within centrosome, perpendicular to each

other. Each centriole consists of nine evenly spaced clusters of three microtubules

arranged in a circle. The microtubules have longitudinal orientation and are parallel to

each other.

Before mitosis, the centrioles in the centrosome replicate and form two pairs. During

mitosis, each pair moves to the opposite poles of the cell, where they become

microtubuleorganizing centers for mitotic spindles that control the distribution of

chromosomes to the daughter cells.

Figure17: Diagram of centrioles structure

Cilia:

Cilia (sing., cilium) are involved in movement. Motile structure use to move

something like the ciliated cells that line our respiratory tract sweep debris trapped

within mucus back up the throat. This helps keep the lungs clean by rhythmic

beating. Similarly, ciliated cells move an egg along the oviduct, where it will be

fertilized by a flagellated sperm cell.

Origin of cilia from centrioles, each centrioles give only one cilium, so ciliated

cells have many centioles embedded in cytoplasm under cell membrane called

basal body. Basal bodies associated structures firmly anchor cilia in the apical cell

cytoplasm.

Cilia have another function; act as receptor in special cells (rods and cones cells of

the eyes retina).

Flagella

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Flagella (sing. Flagellum) is motile projection use to move cell itself, like tail of

sperm. Have an inner core of microtubules within a covering of plasma membrane.

Flagellum is the same structure of cilium but always single and extremely longer.

Figure 18: show the different between cilia and flagellum motion

Clinical application

The importance of normal cilia and flagella is illustrated by the occurrence of a

genetic disorder. Some individuals have an inherited genetic defect that leads to

malformed microtubules in cilia and flagella. Called immotile cilia syndrome

1. These individuals suffer from recurrent and severe respiratory infections. The

ciliated cells lining respiratory passages fail to keep their lungs clean. (chronic

respiratory infections)

2. They are also unable to reproduce naturally due to the lack of ciliary action to

move the egg in a female or the lack of flagella action by sperm in a male.

(Immotile sperm).

Filaments

Each cytoskeletal filament type is formed by polymerization of a distinct type of

minute protein subunit and has its own characteristic shape

and intracellular distribution.

There are three types of filaments:

Microfilaments, intermediated filaments and thick filaments

Microfilament (thin filament or known as actin filaments):

Microfilaments are the thinnest structures of the cytoskeleton usually occur in

bundles or other groupings.

They are composed of the protein actin and are most prevalent on the peripheral

regions of the cell membrane.

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Structure of actin protien is fine strands of globular actin (G-actin).

These structural proteins shape the cells, and are involved in cell movement and

movement of the cytoplasmic organelles. The microfilaments are distributed

throughout the cells and are used as anchors at cell junctions. The actin

microfilaments also form the structural core of microvilli (non motile cellular

membrane protrusions that increase the surface area for diffusion and minimize

any increase in volume such as the epithelial cells of small intestines) and the

terminal web just inferior to the plasma membrane.

Intermediate filaments, as their name implies, are intermediate in size between

microtubules and actin filaments.

Several cytoskeletal proteins that form the intermediate filaments have been identified

and localized.

Their structure and function differ according to the type of cell.

1. Keratin filaments. In skin cells, these filaments terminate at cell junctions,

where they stabilize the shape of the cell and their attachments to adjacent

cells.

2. Vimentin filaments are found in many mesenchymal cells.

3. Desmin filaments are found in both smooth and striated muscles.

4. Neurofilament proteins are found in the nerve cells and their processes.

5. Glial filaments are found in astrocytic glial cells of the nervous system.

6. Lamin intermediate filaments are found on the inner layer of the nuclear

membrane.

The presence of a specific type of intermediate filament in tumors can often reveal the

cellular origin of the tumor, information important for diagnosis and treatment of the

cancer. Identification of intermediate filament proteins by means of

immunocytochemical methods is a routine procedure. One example is the use of

Glial Fibrillary Acidic Proteins (GFAP) to identify astrocytomas, the most common

type of brain tumor.

Finally the thick filaments in muscle tissues are the actin filaments fill the cells and

associated with myosin proteins to induce muscle contractions.

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Inclusions

The cytoplasmic inclusions are temporary non-living structures that accumulate in the

cytoplasm of certain cells not able to carry out any metabolic activity and are not

bound by membranes. Inclusions are stored nutrients, secretory products, and pigment

granules. Examples of inclusions are:

Glycogen: Glycogen granules is the most common form of glucose in animals and is

especially abundant in cells of muscles, and liver

Lipids: Lipids are triglycerides in storage form the common form of inclusions not

only are stored in specialized cells (adipocytes) but also are located as individuals

droplets in various cell type especially hepatocytes. These are fluid at body

temperature and appear in living cells as refractile spherical droplets.

Crystals: Crystalline inclusions have long been recognized as normal constituents of

certain cell types such as Sertoli cells and Leydig cells of the human testis, and

occasionally in macrophages.It is believed that these structures are crystalline forms

of certain proteins which is located everywhere in the cell such as

in nucleus, mitochondria, endoplasmic reticulum, Golgi body, and free in cytoplasmic

matrix.

Pigments: The most common pigment in the body, besides hemoglobin of red blood

cells is melanin, manufactured by melanocytes of the skin and hair, pigments cells of

the retina and specialized nerve cells in the substantia nigra of the brain. These

pigments have protective functions in skin and aid in the sense of sight in the retina

but their functions in neurons is not understood completely. Furthermore, cardiac

tissue and central nervous system neurons shows yellow to brown pigment

called lipofuscin, some believed that they have lysosomal activity.

This type of inclusion called Endogenous pigment because is formed by the cells,

while other type of inclusion come from outside called exogenous like tattoo marks,

carotene and dust

the epithelial surface of lung alveoli where it ingests inhaled particulate matter known

as dust cells.

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Figure 19: show the inclusion body (lipofuscin) in neuron

Nucleus

The nucleus (nuclei, plural) the largest component of a cell, frequently appears

as rounded, oval, flat, kidney shape, horse shoe shape, segmented or lobulated

structure.

Position of nucleus often near the center of the cell but in some cells the

nucleus located eccentric, basal or peripheral.

Found in all eukaryotic cells except mature red blood cells of mammals do not

have a nucleus, or are nonnucleated.

Most cells have a single nucleus called mononucleated, some cells have two

nucleus called binucleated as in liver cells (hepatocyte) or other cells may

exhibit multiple nuclei called multinucleated as

osteoclast and skeletal muscles.

The nucleus stores genetic information. Every cell in

the body contains the same genes.

The nucleus of a non dividing cell consists of the

following components:

The nucleus consists of the following parts:

1. Nucleolemma or nuclear membrane (karyotheca)

2. Nuclear sap or karyolymph or nucleoplasm

3. Chromatin network or fibres

4. Nucleolus

1. Nuclear Envelope or nuclear membrane(karyotheca)

The nuclear envelope forms a selectively permeable barrier (double membrane)

between the nucleus and cytoplasmic compartments.

Electron microscopy reveals that the envelope has two concentric membranes the

outer one is called ectokaryotheca and inner one is termed endokaryotheca

Figure 20:

Anatomy of

nucleus

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separated by a narrow perinuclear space. This space and the outer nuclear

membrane are continuous with the extensive cytoplasmic network of the rough

endoplasmic reticulum.

Closely associated with the inner nuclear membrane is a highly organized

meshwork of proteins called the nuclear lamina which stabilizes the nuclear

envelope. Major components of this layer are the class of intermediate filament

proteins called lamins that bind to membrane proteins and associate with

chromatin in no dividing cells.

The inner and outer nuclear membranes are bridged at nuclear pore complexes.

Various core proteins of a nuclear pore complex called nucleoporins. Although

ions and small solutes pass through the channels by simple diffusion, the pore

complexes regulate movement of macromolecules between the nucleus and

cytoplasm. Macromolecules shipped out of the nucleus include ribosomal subunits

and other RNAs associated with proteins, while inbound traffic consists of

chromatin proteins, ribosomal proteins, transcription factors, and enzymes.

Figure 21: Nuclear envelop anatomy

Medical Application

Certain mutations in the gene coding for lamin A are associated with a subtype

of the disorder progeria, which causes premature aging.

Functions of nuclear envelop are regulate the entry of proteins (histone and

hormones) to the nucleus and export of RNAs from nucleus to the cytoplasm.

Also encloses the nucleus and separates the genetic material of the cell from the

cytoplasm of the cell. And it serves as a barrier to prevent passage of macro-

molecules freely between the nucleoplasm and the cytoplasm.

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2. Chromatin material

Chromatin is the combination of DNA molecules and proteins that make up the

chromosomes. Chromatin can coil tightly to form visible chromosomes during

cell division. Most of the time, however, the chromatin is uncoiled. Individual

chromosomes cannot be distinguished and the chromatin appears grainy in

electron micrographs of the nucleus.

(This will be discussed in details in molecular biology and genetics lectures)

3. Nucleolus

Micrographs of a nucleus do show one or more dark regions of the chromatin

with spongy appearance. These are nucleoli (sing., nucleolus).

The nucleolus is a generally spherical, highly basophilic subdomain of nuclei

in cells, actively making proteins.

The nucleolus is not surrounded by a membrane, it is a densely stained

structure found in the nucleus.

The intense basophilia of nucleoli is due not to heterochromatin but to the

presence of densely concentrated ribosomal RNA (rRNA) that is transcribed,

processed, and complexed into ribosomal subunits in nucleoli.

Chromosomal regions with the genes for rRNA organize one or more nucleoli

in cells requiring intense ribosome production

Molecules of rRNA are processed in the nucleolus and very quickly associate

with the ribosomal proteins imported from the cytoplasm via nuclear pore

complexes. The newly organized small and large ribosomal subunits are then

exported back to the cytoplasm through those same nuclear pores.

Function of nucleolus is ribosome assembly

4. Nucleoplasm or nuclear sap or karyolymph

Chromatin is immersed in a semi fluid medium called the nucleoplasm.

A difference in pH suggests that nucleoplasm has a different composition from

cytoplasm.

The nucleus contains a transparent, semi-solid, granular and homogeneous

matrix during interphase called as nuclear sap or karyolymph (enchylema)

karyolymph is a fluid substance containing many particles and network.

Primarily it is composed of proteinous material and is the main site for

enzyme activity.

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This nuclear sap also shows variable appearance during different stages of cell

division.

Nuclear constituents:

The nucleus contains RNA, DNA, proteins of two kinds, histone and nonhistone;

some lipids; various organic phosphorus compounds; and various inorganic

compounds, mostly salts.

Deoxyribonucleoproteins:

These largely form the chromosomes; consist primarily of histone and DNA in

about equal amounts. However, chromosomes also contain non-histone proteins in

smaller amounts.

Unlike histones (basic), most of the nonhistone proteins are acidic, and they vary

qualitatively in different cell types of the same organism.

Both histones and nonhistone proteins are synthesized in the cytoplasm and enter

the nucleus through the nuclear envelope.

Histones are synthesized only when DNA is replicated, whereas nonhistone

proteins are synthesized continuously.

Histones induce a compact structure in the chromosome.

Histones are also considered as stabilizers against heat damage and against

nucleases.

Activation and repression of genes expression are thought to be carried out by

nonhistone proteins.

The mechanism by which this is done in eukaryotic cells is less clear than it is in

prokaryotic cells.

All the proteins are synthesized in the cytoplasm and then transported into the

nucleus.

Functions of nucleus are:

1. Controls the heredity characteristics of an organism.

2. Responsible for regulation of protein synthesis (gene expression), cell division,

growth and differentiation.

3. Stores heredity material in the form of deoxy-ribonucleic acid (DNA) strands.

4. Stores ribonucleic acid (RNA) in the nucleolus.

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5. Site for transcription process in which messenger RNA (m RNA) are produced

for protein synthesis.

6. Nucleolus produces ribosomes.

7. Regulates the integrity of genes and gene expression.

So, the nucleus called the control center of a cell.

N

H.W. Why the malignant cells have large nucleoli?