Cell 2

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CYTOPLASMIC ORGANELLES

RIBOSOMES
• Ribosomes are composed of rRNA and protein. They
consist of large (60S) and small (40S) subunits.

Polysomes :
• consist of a single (mRNA) that is being translated by
several ribosomes at the same time.
• The ribosomes move on the mRNA from the 5' end
towards 3' end.
ENDOPLASMIC RETICULUM

• Rough Endoplasmic Reticulum :

• RER has a single lipid bilayer continuous with the outer


nuclear membrane.
• It is organized into stacks of large flattened sacs called
cisternae.
• RER synthesize proteins that are destined for the Golgi
apparatus, secretion, the plasma membrane, and lysosomes.
(e.g. pancreatic acinar cells).
SMOOTH ENDOPLASMIC RETICULUM
Smooth Endoplasmic Reticulum

• SER is a network of membranous sacs, vesicles, and


tubules continuous with the RER, but lacking ribosomes.

• SER contains enzymes involved in the synthesis of


phospholipids, triglycerides, and sterols
Functions of SER :

o Detoxification Reactions :
Hydroxylation.
Conjugation.
o Glycogen Degradation and Gluconeogenesis
o Reactions in Lipid Metabolism
o Sequestration and Release of Calcium Ions
››MEDICAL APPLICATION
• Jaundice is caused by accumulation of bilirubin, which are normally
metabolized by SER enzymes in cells of the liver and excreted as bile.

• osteogenesis imperfecta bone cells synthesize and secrete defective


procollagen ,very weak bone tissue, this is due to defect in RER and
ERAD.
GOLGI APPARATUS
GOLGI APPARATUS
• consists of disc-shaped smooth cisternae (dictyosomes),
membrane-bound vesicles.

• two distinct faces:


• The cis (forming) face is associated with the RER.
• The trans (maturing) face is often oriented toward the
plasma membrane.

• Important in glycosylation, phosphorylation, sulfation, etc.


• Takes part in synthesis, concentration & storage of
secretory products.
Forward movement COP-II
retrograde movements COP-I
MEDICAL APPLICATION
Hyperproinsulinemia :
failure of a peptidase to cleave proinsulin to insulin and C-
peptide in the Golgi apparatus.

I-Cell Disease :
AR, caused by deficiency of N-acetylglucosamine-
phosphotransferase, which phosphorylates mannose residues
to mannose 6-phosphate on N-linked glycoprotein in Golgi
Apparatus
LYSOSOMES
• spherical membrane-enclosed organelles that are contain
enzymes required for intracellular digestion.

•Primary lysosomes formed by budding from the trans side


of the Golgi apparatus.
•Secondary lysosomes are formed by the fusion of the
primary lysosome with the substrate to be degraded.
• All lysosomal enzymes are acid hydrolases, with
optimal activity at a pH of approximately 5.0.
MEDICAL APPLICATION
Glycogen-Storage Disease Type II (Pompe Disease) :

• an AR disorder results from deficiency of acid alpha-


glucosidase, which is required for the degradation of glycogen.
• Glycogen accumulation can leads to enlargement and
dysfunction of the entire organ involved (e.g. cardiomyopathy).
RESIDUAL BODIES

•The indigestible
compounds are usually
exocytosed.

•The unreleased
indigestible compounds
in long-living cells
appear as lipofuscins or
aging pigments.
RESIDUAL BODIES IN LUNG CELLS
PEROXISOMES
• heterogeneous group of small, spherical organelles with
a single membrane.

Functions:

• Synthesis and degradation of hydrogen peroxide.


• Oxidation of very long chain fatty acids (> C24).
• Phospholipid exchange.
• Bile acid synthesis.
PEROXISOMES (MICROBODIES )
MEDICAL APPLICATION
Peroxisome Deficiency :
patients fail to oxidize very long chain fatty acids and
accumulate bile acid precursors.

• most common disorders are:


• Zellweger (cerebrohepatorenal) syndrome.
• Neonatal adrenoleukodystrophy.
Proteasomes
• Non membranous
protein complexes.
• degrade denatured or
nonfunctional
polypeptides.
• Alzheimer’s disease
and Huntington’s
disease caused by
protein aggregates due
to Failure of
proteasomes.
MITOCHONDRIA
MITOCHONDRIA

• synthesize adenosine triphosphate (ATP)


• double-stranded circular DNA , proteins.
• Mitochondria have two membranes.
Outer Membrane
• smooth, continuous, and highly permeable.
• abundance of porins, an integral membrane protein.
Intermembrane Compartment :
• It contains enzymes that use ATP to phosphorylate other
nucleotides (creatine phosphokinase and adenylate kinase).
Inner Membrane
• impermeable to most small ions (Na, K, H) and small
molecules (ATP, adenosine diphosphate, pyruvate).
• high content of the lipid cardiolipin.
• Carnitine is required to transport fatty acids.
• numerous infoldings, called cristae.
• They contain, enzymes for electron transport and oxidative
phosphorylation.
Matrix :
• The matrix is enclosed by the inner membrane and
contains:
Dehydrogenases :
• oxidize (pyruvate, amino acids, fatty acids).
• generate reduced (NADH) and (FADH) for use by the
electron transport chain and energy generation.
• Mitochondrial DNA is always inherited from the mother,
resulting in transmission of diseases of energy
metabolism.
• Intramitochondrial granule : contain calcium and
magnesium.
• Myoclonic epilepsy with ragged-red fibers
(MERRF): skeletal muscle, inherit mitochondrial
DNA with a mutated gene for lysine-tRNA,
leading to defective synthesis of respiratory
chain protein.
Mitochondria

Two types of cristae: tubular-like and plate-like.


Most cells contain mitochondria with plate-like cristae. Steroid
secreting cells (eg. Adrenal, gonadal cells) have tubular cristae
CYTOSKELETON
MICROTUBULES

• Small hollow cylindrical unbranched tubules 25 nm in diameter with a 5nm thick


wall.

• Made of 13 tubulin protofilaments arranged side by side around a central core


• The heterodimer, the subunit
of microtubule,is composed of
α and β tubulin molecules.

• It is organized into a spiral


during polymerization.

• A total of 13 units are


present in one complete
turn of the spiral.
Microtubules play a role in:

• Chromosomal movement during meiosis and mitosis.


• spindle formation.
• Intracellular vesicle and organelle transport.
• Ciliary and flagellar movement.
Kinesins:
Motor protein responsible for
moving vesicles and organelles
away from cell center.

Dyneins:
Responsible for movement
on microtubule towards the
cell center.
•Microtubule formation directed by microtubule organizing
center.
•Is under control of concentration of Ca 2+ & microtubule
associated proteins (MAPs).
Microtubule

Microtubule
organizing center
CHEDIAK - HIGASHI SYNDROME :
• Defect in microtubule polymerization .

• is an autosomal recessive immunodeficiency disorder


characterized by abnormal intracellular protein transport.

• Leads to delayed fusion of phagosomes with lysosomes


in leukocytes
Centrioles

A pair of cylindrical structures


with
their long axis perpendicular to
each
other.

Each is composed of 9 sets of


Microtubule triplets arranged in
the
fashion of pinwheel.
Functions of centrioles

Non-dividing cells:
•Polymerization of long single microtubules that radiate
throughout the cytoplasm

•Maintain cell shape

•Transportation of substances

Dividing cells:
•Form mitotic spindles
Microfilaments

Actin filaments
Microfilaments

•Made up of polymers of the protein actin

•Actin present as globular form (G-actin) & filamentous form


(F-actin).

•F-actin polymerizes forming helically entwined actin chains


• These chains easily dissociate &reassemble with changes in levels of Ca 2+ & cAMP change.
Microfilaments (Ankyrin)

Integral protein

Ankyrin anchors
actin-filaments to the
integral proteins of
Ankyrin
The plasma membrane
Microfilaments (Dystrophin)

Transmembrane
protein
Dystroph that links:
in

Short actin filaments


beneath plasma
membrane

Extends across
Dystroph
in
plasma
membrane to bind to
extracellular matrix
Microfilaments
(Dystrophin & muscular dystrophy)

Genetic disorder due to


mutation in gene coding for
the Actin binding protein,
dystrophin
Intermediate filaments

• diameter averaging 10 nm.


• are stable, confer increased mechanical stability to cell structure.
• subunits are coiled, rod-like dimers that form antiparallel tetramers
Intermediate filaments

• Vimentin : in cells of mesenchymal origin; may contribute to position the


nucleus in the cell,
• Desmin : Z-disks of skeletal muscle cells, ensure uniform tension
distribution
• Glial fibrillary acid protein : characteristic of the cytoplasm of glial cells
(astrocytes)
• Neurofilaments : formed by three distinct proteins, they are present in the
cytoplasm of neurons
• Keratins : in cells of the skin for resistance to friction & cell to cell
adhesion
Apoptosis

Cellular injury, DNA damage, or decreased hormonal stimulation leads


to inactivation of Bcl2.
Lack of Bcl2 allows cytochrome c to leak from the inner mitochondrial
matrix into the cytoplasm and activate caspases.
caspases activate proteases and endonucleases.
• Dying cell shrinks, cytoplasm
become more eosinophilic.
• Nucleus condenses and
fragments in an organized
manner.
• Apoptotic bodies fall from the
cell and are removed by
macrophages; apoptosis is not
followed by inflammation.
• A 42-year-old woman comes to the physician for a follow-up
examination after two separate Pap smears have shown dysplastic
epithelial cells. Results of a molecular diagnostic test show DNA that
encodes high-risk versions of the human papillomavirus E6 and E7
proteins. The viral E6 protein binds to the cellular p53 tumor
suppressor gene, causing it to be degraded. Which of the following
best describes the mechanism by which the E6 protein causes cervical
cancer?
• (A) Arrests the cell cycle
• (B) Enhances tissue invasion and metastasis
• (C) Inhibits telomerase expression
• (D) Prevents apoptosis
• (E) Sustains angiogenesis
• An experiment is conducted in which the mitochondrial content of various tissues
is studied. It is found that the mitochondrial content is directly proportional to
the amount of energy one cell is required to generate and expend. The
mitochondrial content is most likely greatest in which of the following types of
cells?
• (A) Cardiac muscle cells
• (B) Chondrocytes
• (C) Endothelial cells
• (D) Epidermal cells
• (E) Hepatocytes
• (F) Osteocytes
• (G) White adipocytes

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