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CYTOPLASMIC ORGANELLES

RIBOSOMES

• composed of rRNA and protein.


• consist of large (60S) and small (40S) subunits.

Polysomes/polyribosomes :
• 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 :

• has a single lipid bilayer.


• It is organized into stacks called
cisternae.
• RER synthesize proteins that are
destined for the
• Golgi apparatus,
• secretion,
• plasma membrane,
• lysosomes.
(e.g. pancreatic acinar cells).
Smooth Endoplasmic Reticulum

• network of membranous sacs,


vesicles, and tubules.
• continuous with the RER,
• lacking ribosomes.

• SER contains
• enzymes involved in the
synthesis of phospholipids,
triglycerides, and sterols
(steroid hormones)
Functions of SER :

o Detoxification Reactions :
Hydroxylation (adding a
hydroxyl group).
Conjugation (make the insoluble
soluble to get rid of it).
o Glycogen Degradation to get glucose and
Gluconeogenesis
o Reactions in Lipid Metabolism
o Sequestration and Release of Calcium Ions, important in
muscle cells
››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.
Conjugation of insoluble bilirubin (bile salt) wont occur.

• osteogenesis imperfecta bone cells synthesize and secrete defective


procollagen ,very weak bone tissue, this is due to defect in RER and
ERAD.
GOLGI APPARATUS
• consists of disc-shaped smooth
cisternae (dictyosomes), membrane-
bound vesicles.
• two distinct faces:
• The cis (forming) face is
associated/near with the RER.
• The trans (maturing) face is often
oriented toward the plasma membrane.
• Important in glycosylation,
phosphorylation, sulfation. E.g post-
transcriptional modifications of proteins
and lipids
• Takes part in synthesis, concentration &
storage of secretory products.
Forward movement COP-II
retrograde movements COP-I
MEDICAL APPLICATION (FAULTY GOLGI)

Hyperproinsulinemia :
elevated levels of proinsulin in serum resulting from a failure
of a peptidase to cleave proinsulin to insulin and C-peptide
in the Golgi apparatus. (they will always be hungry and lack
sugar)

I-Cell Disease :
AR (autosomal recessive), 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
• contain enzymes required for
intracellular digestion.
•Primary lysosomes have not yet
acquired the material to be digested
•Secondary lysosomes is primary +
substrate.
• 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) : if those
hydrolytic enzymes are not functioning it will cause this
disease

• AR disorder
• results from deficiency of acid alpha-glucosidase which breaks
down glycogen.
• Glycogen accumulation
• can leads to enlargement and dysfunction of the entire organ
involved (e.g. cardiomyopathy).
RESIDUAL BODIES

•Lysosomes containing
indigestible compounds are called
residual bodies. (definition)

•The indigestible
compounds are usually
exocytosed.

•The unreleased
indigestible compounds
in long-living cells
appear as lipofuscins or
aging pigments
(examples of residual
bodies).
PEROXISOMES (THEY ARE THE SECOND
DETOXIFICATION ORGANELLES AFTER
SER)

• 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.
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: destroys misfolded protein
• 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

• 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). It is impermeable
Inner Membrane
• impermeable to most small ions (Na,
K, H) and small molecules (ATP,
ADP, pyruvate).
• high content of the lipid cardiolipin.
(Reason of impermeablility)
• Carnitine is required to
transport fatty acids.
• numerous infoldings, called cristae.
• They contain, enzymes for electron
transport and oxidative
phosphorylation.
LOOP OF DNA INHERITED FROM THE
MOTHER ONLY
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.
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
DISEASE
• 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)
• mitochondrial DNA with a mutated gene for
lysine-t RNA in skeletal muscle
• defective synthesis of respiratory chain protein.
CYTOSKELETON
MICROTUBULES

Microtubules play a role in:

• Chromosomal movement during meiosis and mitosis.


• spindle formation.
• Intracellular vesicle and organelle transport.
• Ciliary and flagellar movement
Structure of microtubules

• cylindrical unbranched
tubules 25 nm in diameter
with a 5nm thick wall.
• heterodimer composed of
α and β tubulin molecules.

• It is organized into a spiral


during polymerization.

• A total of 13 protofilament
present in one complete
turn of the spiral.
TRANSPORT PROTEINS (WALKING)

Kinesin: Anterograde
Motor protein responsible for
moving vesicles and organelles
away from cell center.

Dynein: Retrograde
Responsible for movement
on microtubule towards the
cell center.
Microtubule
organizing
center

•Microtubule formation directed by microtubule


organizing center.
•Is under control of concentration of Ca 2+ &
microtubule associated proteins (MAPs).
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


• long axis perpendicular to each
• other.

• 9 sets of Microtubule triplets


• arranged in pinwheel fashion .
9 triplets
shown
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
Dystroph protein
in that links:

Short actin filaments


beneath plasma
membrane

Dystroph Extends across


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

• are stable
• confer increased mechanical
stability to cell structure.
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 (programmed
cell death)

• 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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