The Cell Functional and structural unit of all living organisms. Complex organisms consist of many cells and extracellular matrix.

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The Cell

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The Cell

• Functional and structural unit of all living organisms.

• Complex organisms consist of many cells and extracellular matrix.

• Cells of multicellular organisms have a variety of

• Cells of multicellular organisms have a variety of functional and morphological specializations

• Differentiation – when cells assume specialized structure and function.

• Cytoplasm contains organelles with a defined function.

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Prokaryotic cells

• Found only in bacteria.

• Small (1–5 µm long)

• Have a cell wall outside the plasmalemma

• Lack a nuclear envelope separating the genetic material (DNA) from other cellular constituents.

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• Have no histones (specific basic proteins) bound to their DNA

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Eukaryotic cells

• Cells are larger

• Distinct nucleus surrounded by a nuclear envelope.

• Histones are associated with the genetic material

• Histones are associated with the genetic material

• Numerous membrane-limited organelles in the

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Cell Components

Cell is composed of: cytoplasm and nucleus.

• Individual cytoplasmic components are not clearly distinguishable in common hematoxylin and eosin-stained preparations

• Nucleus appears intensely stained dark blue or black.

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Cytoplasm

Composed of a matrix, or cytosol, in which are embedded the organelles (bounded by

membranes), the cytoskeleton (provides structural support for the cell and its organelles) and deposits of carbohydrates, lipids, and pigments.

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• Cytoplasm of eukaryotic cells is divided into

compartments by membranes which concentrate enzymes and the substrates, thus increasing the efficiency of the cell.

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Electron Micrograph of a cell

ER- Endoplasmic reticulum; F – Fibril; M –Mitochondria; NE-Nuclear envelop; PM – Plasma Membrane; L- Lysosome; IS-Intercellular space; G- Golgi apparatus; V – Secretory vesicle; N – Nucleus; C - Adjacent Cell

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Plasma Membrane (Plasmalemma - PM)

• External limit of the cell with a continuum between the interior of the cell and extracellular

macromolecules.

• Composed of phospholipids, cholesterol, proteins (integrins), and chains of oligosaccharides.

• Membranes range from 7.5 to 10 nm in thickness.

• Membranes range from 7.5 to 10 nm in thickness.

• External lipid membrane surround all cells

• Cell interacts with two types of external environment; adjacent cells, from which it is separated by the

intercellular space and extracellular matrix as represented by collagen fibrils.

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• Electron micrographs reveal that the plasmalemma and other organellar membranes—exhibit a

trilaminar structure after fixation in osmium tetroxide - unit membrane.

• Three layers are produced by the deposit of

reduced osmium on the hydrophilic groups present on each side of the lipid bilayer.

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Functions

• Transfer of nutrients and metabolites

• Attachment of the cell to adjacent cells and extracellular matrix

• Communication with the external environment.

• Selective barrier that regulates the passage of certain materials into and out of the cell and certain materials into and out of the cell and facilitates the transport of specific molecules.

• Keep constant the intracellular milieu, which is different from the extracellular fluid.

• Membranes carry out a number of specific recognition and regulatory functions

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Membrane structure

• Cell membranes are composed of lipid and protein.

• Lipid in the cell membrane form a bilayer sandwiched between two layers of protein.

• Membrane proteins with the fluid nature of the lipid bilayer constitutes the basis of the fluid mosaic model for

membrane structure which was proposed in the early 1970s by Singer and Nicholson.

1970s by Singer and Nicholson.

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• Membrane phospholipids, such as

phosphatidylcholine (lecithin) and

phosphatidylethanolamine (cephalin), consist of

two long, nonpolar (hydrophobic) hydrocarbon

chains linked to a charged (hydrophilic) head group.

• Phospholipids are stable when organized into a double layer with their hydrophobic (nonpolar) double layer with their hydrophobic (nonpolar)

chains directed toward the center of the membrane and their hydrophilic (charged) heads directed

outward.

• Cell membranes consist of a bilayer of phospholipid molecules that are amphipathic, consist of a polar,

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• Proteins are a major molecular constituent of membranes (about 50% w/w in the plasma membrane)

- Integral (intrinsic) proteins are incorporated within the lipid bilayer.

- Some integral proteins span the membrane one or more times, from one side to the other, they are called one-pass or multipass transmembrane proteins.

- Peripheral (extrinsic) proteins exhibit a looser association - Peripheral (extrinsic) proteins exhibit a looser association

with membrane surfaces and are held to the surface by weak electrostatic forces.

• Membrane proteins are synthesized in the RER, completed in the Golgi apparatus and are transported in vesicles to the cell surface

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Cholesterol

• Breaks up the close packing of the phospholipid long chains, and this disruption makes the

membrane more fluid.

• Constituent of cell membranes.

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• Cell controls the fluidity of the membranes through the amount of cholesterol present.

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Glycocalyx

• External surface of the cell showing a carbohydrate-rich

region.

• Composed of carbohydrate chains linked to membrane

proteins, lipids, glycoproteins and proteoglycans.

• Has a role in cell recognition and attachment to other

cells and to extracellular molecules. cells and to extracellular molecules.

• Involved in the formation of intercellular adhesions and

in the adsorption of molecules to the cell surface

• Provides mechanical and chemical protection for the

plasma membrane.

• Mediate the flow of materials and information into and

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Movement across the plasma membrane

• Na+, K+, and Ca2+, are transported across the cell membrane through integral membrane proteins, using energy from the breakdown of adenosine triphosphate (ATP).

• Mass (bulk) transfer of material also occurs through the plasma membrane - endocytosis.

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the plasma membrane - endocytosis.

Release of material in bulk - exocytosis.

Pinocytosis- process by which cells ingest small

molecules of extracellular fluids or liquids

Phagocytosis- ingestion or intake of large solid

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Nucleus

• Largest organelle

Its substance is referred to as the nucleoplasm,Bounded by the nuclear envelope or membrane.

• Contains the genetic material (blueprint - stored in the form of

deoxyribonucleic acid (DNA) arranged in the form of chromosomes).

• Can replicate its DNA, synthesize and process the three types of • Can replicate its DNA, synthesize and process the three types of

RNA -ribosomal (rRNA), messenger (mRNA), and transfer (tRNA).

• Rounded or elongated structure, in the center of the cell.

Components are the nuclear envelope, chromatin, nucleolus, and nuclear matrix.

• Size and morphology in normal tissue is uniform while irregular, variable size, and atypical chromatin patterns in cancer cells .

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Schematic diagram and electron micrograph of the nucleus

EC - Euchromatin HC – Heterochromatin F - Pars Fibrosa G – Pars Granulosa Nu – Nucleolus M – Mitochondria ER – Endoplasmic Reticulum

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Nuclear Envelope

• Surrounded by two parallel membranes separated by a

narrow space (40-70 nm) called the perinuclear

cisterna.

Paired membranes and the space make up the nuclear

envelope.

• Associated with the internal membrane of the nuclear

• Associated with the internal membrane of the nuclear

envelope is a protein structure called the fibrous

lamina, which helps to stabilize the nuclear envelope,

composed of three proteins called lamins A, B, and C.

• Where the inner and outer membranes fuse, there are

gaps, the nuclear pores, that provide controlled

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Pores are not open but show a pore complex made of more than 100 proteins.

• Nuclear envelope is impermeable to ions and

molecules of all sizes, the exchange of substances between the nucleus and the cytoplasm is made only through the nuclear pores.

• Ions and molecules with a diameter up to 9 nm pass

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• Ions and molecules with a diameter up to 9 nm pass freely through the nuclear pore without consuming energy, molecules and complexes larger than 9 nm are transported by an active process and uses

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Chromatin

• Chromosomes in a degree of uncoiling.

• Two types of chromatin can be distinguished

- Heterochromatin is dense

- Euchromatin is the less coiled portion of the

chromosomes, lightly stained

• Composed of coiled strands of DNA bound to basic

• Composed of coiled strands of DNA bound to basic proteins (histones).

• Basic structural unit of chromatin is the

nucleosome, which consists of four types of histones - H2A, H2B, H3, and H4

• Nonhistone proteins are also associated with chromatin.

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Nucleolus

• Spherical structure rich in rRNA and protein.

• Basophilic when stained with hematoxylin and eosin.

• Consists of three components:

- Nucleolar organizer - sequences of bases that code for rRNA.

- Pars fibrosa - densely packed 5- to 10-nm ribonucleoprotein fibers which are closely associated with the nucleolar organizers

- Pars granulosa consists of 15- to 20-nm granules (maturing ribosomes).

• Proteins synthesized in the cytoplasm, become associated with rRNAs in

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• Proteins synthesized in the cytoplasm, become associated with rRNAs in the nucleolus; ribosome subunits then migrate into the cytoplasm.

Heterochromatin is often attached to the nucleolus

(nucleolus-associated chromatin)

• rRNAs are synthesized and modified inside the nucleus - move into the nucleolus to receive proteins

- organized into small and large ribosomal subunits - migrate to the cytoplasm through the nuclear pores.

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Nuclear Matrix

• Component that fills the space between the chromatin and the nucleoli in the nucleus

• Composed of proteins, metabolites, and ions.

• Contains a continuous fibrillar structure forming the

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Mitochondria

• Spherical or filamentous organelles 0.5–1 m wide and length of 10 m.

• Accumulate in parts of the cytoplasm at which the utilization of energy is more intense, such as the apical ends of ciliated cells, middle piece of

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apical ends of ciliated cells, middle piece of spermatozoa, base of ion-transferring cells.

• Transform the chemical energy of the metabolites present in cytoplasm into energy that is easily

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Composed of an outer and an inner mitochondrial

membrane

- Inner membrane projects folds (cristae) into the

interior.

- Protein secreting cells have shelf-like cristae

- Steroid secreting cells eg, adrenal gland contain tubular cristae.

tubular cristae.

• Cristae

- Increase the internal surface area of mitochondria - Contain enzymes and other components of

oxidative phosphorylation and electron transport systems.

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• Membranes enclose

two compartments and space between the two membranes is termed the intermembrane

space.

• Inner membrane

encloses the other compartment—the

intercristae, or matrix,

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31 compartment—the intercristae, or matrix, space. • Membranes contain protein molecules.

• The ADP to ATP

phosphorylating system is localized in globular structures

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• Number of mitochondria and cristae in each mitochondrion are related to the energetic activity of the cells in which they reside - cardiac muscle and cells of kidney tubules

Between the cristae is a matrix, rich in protein, DNA, the three varieties of RNA [ribosomal RNA (rRNA), messenger RNA

(mRNA), and transfer RNA (tRNA)] and Ca2+.

• Enzymes for the citric acid (Krebs) cycle and fatty acid -oxidation are found within the matrix space.

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• Mitochondrial ribosomes are smaller than cytosolic ribosomes. • Protein synthesis occurs in mitochondria, a small proportion of

the mitochondrial proteins is synthesized in polyribosomes located in the cytosol.

Electron transport system releases energy through the

formation of ATP from ADP and inorganic phosphate.

• In mitosis, each daughter cell receives approximately half the mitochondria originally present in the parent cell.

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MEDICAL APPLICATION

• Diseases of mitochondrial deficiency are characterized by muscular dysfunction.

• Because of their high-energy metabolism, skeletal muscle fibers are very sensitive to mitochondrial defects.

• DNA mutations or defects occur in the

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• DNA mutations or defects occur in the mitochondria or the cell nucleus cause mitochondrial diseases.

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Ribosomes

• Small electron-dense particles, about 20 x 30 nm in size.

• Composed of four types of rRNA and almost 80 different proteins.

• Two classes:

A: prokaryotes, chloroplasts, and mitochondria

B: eukaryotic cells, composed of two different-sized subunits. B: eukaryotic cells, composed of two different-sized subunits.

• In eukaryotic cells, the RNA molecules are synthesized within the nucleus.

• Their proteins are synthesized in the cytoplasm, enter the nucleus and associate with rRNAs.

• Subunits leave the nucleus to enter the cytoplasm and participate in protein synthesis.

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• Basophilic because of phosphate groups of the constituent rRNA

• Held together by a strand of mRNA to form

polyribosomes (polysomes).

• mRNA carries a message for amino acid sequence of proteins being synthesized by the cell

• Play a crucial role in decoding this message during

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• Play a crucial role in decoding this message during protein synthesis.

• Proteins synthesized for use within the cell which remain in the cytosol are synthesized on

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Endoplasmic Reticulum

• Network of intercommunicating channels and sacs formed by a

continuous membrane, which encloses a space called a cisterna.

• When the cytosolic side of the membrane is covered by

polyribosomes permits the distinction between the two types of endoplasmic reticulum: rough and smooth.

Rough Endoplasmic Reticulum (RER)

• Prominent in cells specialized for protein secretion, such as

• Prominent in cells specialized for protein secretion, such as

pancreatic acinar cells (digestive enzymes), fibroblasts (collagen), and plasma cells (immunoglobulins).

• Consists of saclike and parallel stacks of flattened cisternae,

continuous with the outer membrane of the nuclear envelope.

• “Rough endoplasmic reticulum" alludes to the presence of

polyribosomes on the cytosolic surface of this structure's membrane.

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Functions

• Segregate proteins not destined for the cytosol.

• Glycosylation of glycoproteins,

• Synthesis of phospholipids

• Assembly of multichain proteins

• Posttranslational modifications of newly formed polypeptides.

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• Intracellular storage (lysosomes and specific granules of leukocytes)

• Provisional intracellular storage of proteins for export (pancreas, some endocrine cells)

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Smooth Endoplasmic Reticulum (SER)

• Takes the form of a membranous network within the cell

• Ultrastructure differs from RER in two ways.

- Lacks polyribosomes that characterize RER. SER membranes appear smooth rather than granular.

- Cisternae are more tubular than as stacks of flattened cisternae

• Continuous with the RER. The image cannot be display ed. Your computer may not hav e enough memory to open the image, or the image may hav e been corrupted. Restart y our computer, and then open the file again. If the red x still appears, y ou may hav e to delete the image and then insert it again.

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Functions

• In cells of the adrenal cortex, SER contains enzymes

required for steroid synthesis.

• In liver cells, it is responsible for the oxidation,

conjugation, and methylation processes to degrade certain hormones and neutralize noxious substances such as barbiturates.

• Synthesis of phospholipids for all cell membranes which

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• Synthesis of phospholipids for all cell membranes which

are transferred from the SER to other membranes.

• Contains the enzyme glucose-6-phosphatase which is

involved in the utilization of glucose originating from glycogen in liver cells.

• Participates in the contraction process in muscle cells

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Golgi Complex (Golgi Apparatus)

• Completes modifications, packages, concentrates, stores secretory products and places an address on products that have been synthesized by the cell.

Composed of smooth membrane-limited cisternae.

• Near the Golgi complex, the RER is seen budding off small vesicles that shuttle newly synthesized proteins to the Golgi complex for further processing.

The Golgi cisterna nearest this point is called the forming, convex, or cis face. On the opposite side is the maturing, concave, or trans face, large Golgi vacuoles accumulate.

Golgi vacuoles accumulate.

• Important in the glycosylation, sulfating, phosphorylation, and limited proteolysis of proteins. The image cannot be display ed. Your computer may not hav e enough memory to open the image, or the image may hav e been corrupted. Restart y our computer, and then open the file again. If the red x still appears, y ou may hav e to delete the image and then insert it again.

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Lysosomes

• Spherical

• Sites of intracellular digestion and turnover of

cellular components and cytoplasmic organelles.

• Contain a large variety of hydrolytic enzymes (more than 40) whose main function is intracytoplasmic

digestion

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digestion

• Abundant in cells exhibiting phagocytic activity (macrophages, neutrophilic leukocytes).

• Lysosomal enzymes are capable of breaking down

most biological macromolecules and have optimal activity at an acidic pH.

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• Enveloping membrane separates the lytic enzymes from the cytoplasm

• Lysosomes that have not entered into a digestive event - primary lysosomes, when they fuse with phagosome and empty their hydrolytic enzymes

into the vacuole and digestion follows, it is termed a

secondary lysosome. secondary lysosome.

• Indigestible compounds are retained within the vacuoles which are called residual bodies.

• In some long-lived cells (eg, neurons, heart muscle), large quantities of residual bodies accumulate and are referred to as lipofuscin, or age pigment.

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MEDICAL APPLICATION

• Primary lysosomes release their contents extracellularly, and their enzymes act in the extracellular milieu.

• Lysosomes turns over cytoplasmic organelles

• Lysosomal enzymes acting in the extracellular milieu play a significant role in the response to inflammation or injury.

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inflammation or injury.

• Lysosomes play an important role in the

metabolism of several substances in the human body

• Many diseases have been ascribed to deficiencies of lysosomal enzymes, a specific lysosomal enzyme is absent or inactive.

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Proteasomes

• Protease complexes digest proteins targeted for destruction by attachment to ubiquitin.

• Protein degradation is essential to remove excess enzyme and other proteins that become

unnecessary to the cell after they perform their normal functions

normal functions

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Peroxisomes, or Microbodies

• Spherical membrane-limited organelles whose

diameter ranges from 0.5 to 1.2 µm.

• Utilize oxygen but do not produce ATP

Contain oxidases which oxidize organic substances

• This activity produces hydrogen peroxide (H2O2), which is eliminated by the enzyme catalase, which

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which is eliminated by the enzyme catalase, which is present in peroxisomes.

• Catalases eliminates H2O2 by breaking it down to H20 and O2 molecules

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Secretory Vesicles, or Granules

• Found in cells that store a product until its release is signaled by a metabolic, hormonal, or neural

message.

• Surrounded by a membrane and contain a

concentrated form of the secretory product. concentrated form of the secretory product.

• Secretory vesicles containing digestive enzymes are referred to as zymogen granules.

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Cytoskeleton

• Network of protein filaments and tubules within the cytoplasm

• Serves as the cell structural framework

• Structural proteins which provide for the shaping of

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• Structural proteins which provide for the shaping of cells and movements of organelles, entire cells and intracytoplasmic vesicles.

• Formed by three types of filamentous proteins, microfilaments, intermediate filaments and

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Microfilaments

• Thinnest structures of cytoskeleton

• Composed of protein actin

• Prevalent on the peripheral regions of the cell

membrane

• Shape the cells and contribute to cell and organellar

movement movement

• Distributed throughout the cell

• Used as anchors at cell junctions

• Actin forms the structural core of microvilli and

terminal web inferior to the plasma membrane

• In muscle tissues, actin filaments fill the cells and are

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Intermediate filaments

• Thicker than microfilaments

• More stable

• Several cytoskeletal proteins are identified: - Keratin---epithelial cells (terminate at

desmosomes and hemidesmosomes)

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- Vimentin--- mesenchymal cells

- Desmin--- smooth and striated muscles - Neurofilaments--- nerve cells and processes - Glial filaments---astrocytic glial cells

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Microtubules

• Found in all cell types except red blood cells

• Largest elements of the cytoskeleton

• Hollow unbranched cylindrical structures composed of

two protein subunits α and β tubulin

• Originate from mircotubule organizing centre, the

centrosome which contains a pair of centrioles

• Determines cell shape and function in intracellular

movement of organelles and secretory granules

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Determines cell shape and function in intracellular movement of organelles and secretory granules

• Essential in mitosis forming mitotic spindles

Predominant in cilia and flagella.

• Basis of centrioles and basal bodies of the cilia

• Outer diameter of 24 nm; a dense wall 5 nm thick and a

hollow core 14 nm wide.

• 13 units (protofilament) is present in one complete turn

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(52)

MEDICAL APPLICATION

• Cytoplasmic microtubules play a significant role in the development and maintenance of cell shape.

• Disrupted microtubules result in the loss of cellular asymmetry.

• Microtubules participate in the intracellular

transport of organelles and vesicles eg axoplasmic transport in neurons, melanin transport in pigment transport in neurons, melanin transport in pigment cells, chromosome movements by the mitotic

spindle, and vesicle movements among different cell compartments.

• Microtubules provide the basis for several complex cytoplasmic components, including centrioles, basal bodies, cilia, and flagella.

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Centrioles

• Cylindrical structures (0.15 m in diameter and 0.3–0.5µm in length)

• Composed of microtubules.

• Each centriole shows nine sets of microtubules arranged in triplets.

• Centrosome

• Area of cytoplasm located located near the nucleus

• Major microtubule forming centre

• Site for generating new microtubules and mitotic spindles

• Consists of two centrioles at right angle to each other and matrix

• Each centriole consist of nine clusters of threebsets of fused microtubules arrange in a ring

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arrange in a ring

Close to the nucleus of nondividing cells is a centrosome made of a pair of centrioles.

• Before mitosis, centrioles in the centrosomes replicate and form two pairs which move to the opposite poles of the of the cell during mitosis where they become microtubule organizing centre for mitotic spindles

• Beneath the cell membrane, centrioles induce the formation of basal bodies and organize the development of microtubules in cilia and flagella

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Cilia and flagella

• Motile processes with a highly organized microtubule

core.

• Ciliated cells possess a large number of cilia, each

about 2–3 µm in length.

• Flagellated cells have only one flagellum, with a length

close to 100 µm.

• Spermatozoa are the only cell type with a flagellum

whose main function is to sweep fluid from the surface whose main function is to sweep fluid from the surface of cell sheets.

• Both cilia and flagella possess the same core

organization.

• This core consists of nine pairs of microtubules

surrounding two central microtubules.

This sheaf of microtubules, possessing a 9 + 2 pattern,

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Actin Filaments

• Contractile activity in muscle cells results from an interaction

between two proteins: actin and myosin.

• Actin is present in muscle as a thin (5–7 nm in diameter) filament

• Within cells, actin can be organized in many forms.

- In skeletal muscle, they are integrated with myosin filaments. - In most cells, form a thin sheath just beneath the plasmalemma,

called the cell cortex.

- Intimately associated with several cytoplasmic organelles, vesicles,

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- Intimately associated with several cytoplasmic organelles, vesicles, and granules.

- Associated with myosin and form filaments whose constriction results in the cleavage of mitotic cells.

- Found scattered within the cytoplasm.

- In muscle cells are structurally stable, in nonmuscle cells they readily dissociate and reassemble.

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Intermediate Filaments

• A third filamentous structure is present in eukaryotic cells.

• Cells contain a class of intermediate-sized filaments with an average diameter of 10–12 nm.

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Cytoplasmic Deposits

• Transitory components of the cytoplasm

• Composed of metabolites / substances eg lipid droplets, glycogen, proteins (secretory granules or vesicles).

Colored substances—pigments—are found in cells. They may be synthesized by the cell (eg,

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They may be synthesized by the cell (eg,

melanocytes) or come from outside the body (eg, carotene).

- Lipofuscin present in permanent cells (eg, neurons,

cardiac muscle) that increases in quantity with age,

melanin is abundant in the epidermis and in the

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Cytosol

• The final supernatant produced after the separation of organelles, is called the cytosol.

• Constitutes about half the total volume of the cell.

• Co-ordinates the intracellular movements of organelles and provides an explanation for the viscosity of the cytoplasm.

viscosity of the cytoplasm.

• Contains enzymes that produce building blocks for larger molecules and break down small molecules to liberate energy.

• All machinery to synthesize proteins (rRNA, mRNA, tRNA, and other factors) is contained in the cytosol.

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Cell Component Involved Disease Molecular Defect Morphological Change Clinical Consequence

Mitochondrion Mitochondrial cytopathy Defect of oxidative

phosphorylation

Increase in size and number of muscle mitochondria

High basal metabolism without hyperthyroidism

Microtubule Immotile cilia syndrome Lack of dynein in cilia and

flagella

Lack of arms of the doublet microtubules

Immotile cilia and flagella with male sterility and chronic respiratory infection

Mouse (Acomys) diabetes Reduction of tubulin in pancreatic cells

Reduction of microtubules in cells

High blood sugar content (diabetes)

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Lysosome Metachromatic

leukodystrophy

Lack of lysosomal sulfatase Accumulation of lipid (cerebroside) in tissues

Motor and mental impairment

Hurler disease Lack of lysosomal -L

-iduronidase

Accumulation of dermatan sulfate in tissues

Growth and mental retardation

Golgi complex I-cell disease Phosphotransferase

deficiency

Inclusion-particle storage in several cells

Psychomotor retardation, bone abnormalities

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References