Unit 2 - The Cell Episode 5 Flashcards
are membrane enclosed compartments associated with all the endocytic pathways
restricted to a portion of the cytoplasm near the cell membrane
Early endosomes
are vesicles originating in early endosomes travelling to deeper structures in the cytoplasm
Typically mature into lysosomes
Late endosomes
Early endosomes - Cellular localization
found in the more peripheral cytoplasm
Early endosomes - Morphology
have a tubulovesicular structure
Early endosomes - State of acidification
exhibits only a slightly acidic environment (pH 6.2 to 6.5) than the cytoplasm of the cell
Early endosomes - Function
to sort and recycle (ang clathrin and adaptin) proteins internalized by endocytotic pathways
- Essential Enzyme
- mature into lysosomes
Late endosomes
Late endosomes - cellular localization
positioned near the Golgi apparatus and the nucleus
Late endosomes - Morphology
have a more complex structure and often exhibit onionlike internal
Late endosomes - State of acidification
more acidic, averaging 5.5
Inactive precursor of hydrolase)
released by the late endosomes
Prohydrolase
This help package the hydrolases into vesicles that bud from the trans-golgi network to deliver their contents to endosomes that ultimately will develop into mature lysosomes
Mannose-6-Phosphate receptor (M6P receptor)
Endosomes can be viewed either as __________ cytoplasmic organelles or as ________________________
stable; transient structures
Two different models that explain the origin and formation of the endosomal compartments in the cell:
Stable Compartment Model
Maturation model
describes early and late endosomes as stable cellular
Stable Compartment Model
endosomes and then to lysosomes early endosomes are formed then matures to late endosomes and then to lysosomes
Maturation Model
digestive organelle
Lysosomes
Spherical, with 0.05-0.5 μm diameter
Present a uniformly granular, electro-dense appearance in TEM
Lysosomes
Lysosomes is a membrane-limited vesicles that contain about
40 hydrolytic enzymes
Lysosomes has lysosomal enzymes that can be seen using
histochemical procedure
Lysosomal enzymes synthesized in the rER (rough ER) and sorted in the golgi apparatus based on their binding ability to
M-6-P receptors (Mannose-6-Phosphate receptor)
Most common are hydrolases:
PROTEASOMES, NUCLEASES, PHOSPHATASES, PHOSPHOLIPASES SULFATASE, BETA- GLUCURONIDASE
Lysosomes have a unique membrane that is resistant to the hydrolytic digestion occurring in their _____
lumen
Lysosomal membrane has unusual phospholipid structure that contains cholesterol and a unique lipid called
Lysobisphosphatidic acid
lysosome-associated membrane proteins (lamps), lysosomal membrane glycoproteins (Igps), and lysosomal integral membrane proteins (limps).
represent more than 50% of the total membrane of the proteins
Membrane proteins
Lysosomes and late endosomes contain _________ and __________ that transport the final products of digestion.
proton (H) pumps; transport proteins
proteins are synthesized in the rER and have specific lysosomal targeting signals.
lysosomal membrane
an agent used in the treatment and prevention of malaria, is a lysosomotropic agent that accumulates in the lysosomes. It raises the pH of the lysosomal content, thereby inactivating many lysosomal enzymes. (By raising pH)
Chloroquine
causative agent of Malaria
Plasmodium falciparum
The action of chloroquine on lysosomes accounts for its antimalarial activity; the drug concentrates in the acidic food vacuole of the malaria parasite (Major digestive organelle) and interferes with its digestive processes, eventually
killing the parasite
Three pathways of material delivery for intracellular digestion in lysosomes:
Extracellular large particles
Extracellular small particles
Intracellular particles
such as bacteria, cell debris, and other foreign matenals are engulfed in the process of phagocytosis
Extracellular large particles
phagocytosis occur through your
phagosomes
such as extracellular proteins, plasma-membrane proteins, and ligand- receptor complexes are internalized by pinocytosis and receptor-mediated endocytosis
Extracellular small particles
such as entire organelles, cytoplasmic proteins, and other cellular components are isolated from the cytoplasmic matrix by endoplasmic reticulum membranes, transported to lysosomes, and degraded- autophagy
Intracellular particles
Three well-characterized pathways of autophagy:
Macro- autophagy
Micro- autophagy
Chaperone- mediated autophagy
____________ is a nonspecific process
A portion of the cytoplasm or an entire organelle is first surrounded by the isolation membrane of endoplasmic reticulum, to form a vacuole called _____________which matures into lysosomes
Isolation membrane disintegrates within the hydrolytic compartment of a lysosome
Macroautophagy; autophagosomes
is also a nonspecific process
Cytoplasmic proteins are degraded in a slow, continuous process under normal physiologic conditions
Small cytoplasmic soluble proteins are internalized by invagination of the lysosomal membrane
Microautophagy
the action or process of being turned inside out or folded back on itself
invagination
is a selective process of protein degradation
This process is activated during nutrient deprivation and responsible for the degradation of approximately 30% of cytoplasmic proteins in organs such as the liver and kidney
Chaperone-mediated autophagy
Chaperone-mediated autophagy requires assistance from specific cytosolic chaperones such as heat-shock chaperone protein called
hsc73
Secondary lysosome) 0.2 - 2 UM
active organelles, are generally somewhat larger and have more heterogenous appearance in the TEM because of the wide variety of materials they may be digesting
Heterolysosomes
a debris-filled vacuole resulting from hydrolytic breakdown of the contents of lysosomes
Normal feature of cell aging
Can accumulate as lipofuscin (Lipid-containing residual of lysosomal digestion)
Residual body
Residual body is also known as
Telolysosomes
are cause by pathologic accumulation of undigested substrate in residual bodies due to absence of certain lysosomal enzymes
Lysosomal storage diseases
- lysosomal membrane mutation
Accumulation of autophagic vacuole
Danon disease
Lack of lysosomal acid lipase
lipid product will accumulate (ex. cholestera esters, TAG (Trigylcerol))
Wolman disease
absence of lipids
deficiency of Gluco-cerebrosidase
Gaucher disease
lipids accumulate in brain cells
B-Hexoaminodase A deficiency
Tay-Sachs disease
build up of harmful amount of lipids
B-hexoaminodase deficiency
Sandhoff disease
abnormal amount of lipids build up
Sphinomyelinase deficiency
Niemann-pick disease
absence of a-1-4 glucosidase
glycogen will aggravate
Pompe disease
no protein aspartoacylase
Canavan disease
lysosomal membrane problem
Accumulation of cysteine
Cystinosis
Break songs:
Bibingka
Leaves
Araw-araw
protein destruction
is used by cells to destroy abnormal proteins that are misfolded, denaturated, or contain abnormal amino acids
Proteasome-mediated degradation
It also degrades normal short-lived regulatory proteins that need to be rapidly inactivated and degraded such as mitotic cyclins that regulate cell-cycle progression, transcriptional factors, tumor suppressors, or tumor promoters
Proteasome-mediated degradation
Individual ubiquitin molecules are activated by:
E1 - ubiquitin activating enzymes
E2 - ubiquitin conjugating enzymes
E3 - ubiquitin protein-ligase enzymes
how many molecule of ubiquitin to gave a ubiquitin chain
4
occurs when Ubiquitin molecules are attached end-to-end to a single lysine residue on a substrate protein to form a poly-ubiquitin chain
Polyubiquitination
Malfunction of proteasome-mediated degradation:
- Loss of proteasome function because of mutations in the system of ubiquitin (once magkaroon ng ubiquitin) activating enzymes that leads to a decrease in protein degradation and their subsequent accumulation in the cell cytoplasm
- Accelerated degradation of proteins by overexpressed proteins involved in system
convoluted membranous network
Extends from the surface of the nucleus to the cell membrane
Rough Endoplasmic Reticulum
RER encloses a series of intercommunicating channels and sac, called _______
With the TEM, the rER appears as a series of interconnected, membrane-limited, flattened sacs membrane called ______ with particles studding the exterior surface of the
cisternae
Functions of RER
- synthesis and segregation of proteins not - -
- destined for the cytosol
- initial glycosilation of glycoproteins
- posttranslational modification of newly formed polypeptide
- assembly of multichain proteins
The protein synthetic system of the cell:
Rough Endoplasmic Reticulum
Ribosomes
The cytoplasm of a variety of cells engaged chiefly in protein synthesis are ________ due to presence of RNA
basophilic
The ________ in secretory cells is the light microscopic image of the organelle called the rough endoplasmic reticulum (ER)
ergastoplasm
portion of the cells that stains with basic dye
Ergastoplasm
Protein synthesis the two processes:
Transcription
Translation
production of proteins by the cell begins within the nucleus in which the genetic code for a protein is transcribed from DNA to pre-mRNA then to mRNA after post- transcriptional modifications
Transcription
in which the coded message contained in the mRNA is read by ribosomal complexes to form a polypeptide
Translation
many ribosomes are formed by binding of single cytoplasmic mRNA to many ribosomes
Polyribosome complex
can translate single mRNA
- Can produce many copies of protein
Attach to the cytoplasmic surface of rER
Polyribosome complex
Polyribosome complex is also known as
polysomes
renders the rER unable to export 1-antitrypsin (A1AT), a single amino acid substitution
This leads to decreased activity of A1AT in the blood and lungs and abnormal deposition of defective A1AT within the rER of liver hepatocytes, resulting in emphysema (COPD) and impaired liver function.
alpha-1-antitrypsin deficiency (A1AT)
Several types of ________ inhibit protein synthesis by binding to different portions of bacterial ribosomes
antibiotics
ex of aminoglycosides
(gentamicin, chloramphenicol, fusidic acid) (erythromycin, mutamycin)
non-membranous organelle
Site of protein synthesis which will be transmitted to Golgi complex for packaging and secretion out of the cell
Ribosomes
Svedberg unit of ribosomes
Prokaryotes = 30s - 50s = 70S
Eukaryotes = 40s - 60s = 80s
Ribosomes in cytosol has four segments of rRNA and approximately____ different proteins
80
have two subunits of different sizes and act to catalyze the process of protein translation
Bound to mRNA
ribosomes occupying a single mRNA
intensely basophilic, because of numerous phosphate group present
Polyribosomes
exhibits eosinophilia
lack bound polyribosomes
continuous with RER
Smooth Endoplasmic Reticulum
cisternae are often more tubular and appear as interconnected channels
not basophilic and best seen in TEM
Smooth Endoplasmic Reticulum
Smooth Endoplasmic Reticulum functions:
- glycogen and lipid metabolism
- detoxification reactions
- temporary Ca2+ sequestration
- phospholipid synthesis
very important in lipid metabolism and principle organelles for detoxification and conjugation of noxious organelles
Smooth Endoplasmic Reticulum
Because of these widely disparate functions, numerous other enzymes are associated with the SER, depending on its functional role including
hydrolases, methylases, glucose-6- phosphatase, ATPases, and lipid oxidases
cannot be stained using H & E staining (Hemotoxin and Eosin staining)
composed of smooth membranous saccules containing enzymes
Golgi Apparatus
Golgi apparatus is named after
Camillo Golgi
Camillo Golgi discovered Golgi Apparatus in
1898
Golgi Apparatus functions:
- Completes posttranslational
- modifications of proteins
- Packages and addresses proteins to proper destinations
small membrane-enclosed carriers where material from RER move to the Golgi apparatus
Transport vesicles
has a flattened cisternae located closes to RER
cis-golgi-network (cis face)
larger saccules or vacoules carry completed proten produce organelles away from the golgi
Shipping or trans face (trans-golgi-network)
complex coated transport vesicle
Cop II (co-protein II ) complex
undergo a series of post-translational modifications that involve remodeling of N-linked oligosaccharides previously added in the ER as they travel through the Golgi stacks
Proteins and lipids
middle of trans and cis face
medial-golgi-network
Membrane-enclosed organelles with arrays of enzymes specialized for aerobic respiration and production of ATP
are usually elongated structures with diameter of 0.5-1.0 um and length up to ten times greater
Mitochondria
Mitochondria is present in all cell Except in
RBC and terminal keratinocytes
A CELL WITHIN A CELL
Mitochondria
-has mitochondrial DNA that encode 13 enzymes
- has 2 rRNA and 22tRNA
- Complete system of protein synthesis
Mitochondria
Number of mitochondria is related to the cells energy need:
Cells with high energy metabolism have abundant mitochondria (cardiac cells, cells of some kidney tubules)
Cells with a low-energy metabolism have few mitochondria
Mitochondria of differentiated cells are concentrated in cytoplasmic region where energy utilization is more intense
Mitochondria possess two membranes that delineate distinct compartments:
Inner mitochondrial membrane
Outer mitochondrial membrane
surrounds a space called the matrix (may product: CO2, NADH)
Rich in cardiolipin
Inner mitochondrial membrane
- is in close contact with the cytoplasm
- Voltage dependent
- ion channel (channels that are large permeable)
Ex: Mitochondrial proteins
Outer mitochondrial membrane
intermembrane space contain ____________ that is essential for apoptosis
Cytochrome C
abnormal mitochondria, mutation of mitochondrial DNA
MERRF - Myoclonic Epilepsy with Ragged- Red Fibers
Microbodies (oxidative enzymes)
Membrane-enclosed organelles with arrays of enzymes specialized for aerobic respiration and production of ATP
are spherical organelles enclosed by a single membrane and named for their enzymes producing and degrading hydrogen peroxide, H2O2
Peroxisomes
removes hydrogen atoms that are transferred to molecular O₂ producing H₂O₂
Oxidases
breakdowns H₂O, which is potentially damaging to the cell
Catalase
Peroxisomes forms in two ways:
Building of the precursor vesicle from the ER
Growth and Division of pre-existing peroxisomes
Found in cells that store product until its release by exocytosis is signaled by metabolic. hormonal, or neural message
Surrounded by membrane and contain a concentrated form of secretory products
Secretory Granules
with dense content of digestive enzymes
Zygomen granules
Responsible for transport, storage, and secretion of digestive enzymes
Secretory granules
Polymeric structures composed of equal parts of alpha-tubulin and beta-tubulin
A structure that confer cell rigidity to help maintain cell shape
Can rapidly disassemble and reassemble
Microtubules
MICROTUBULES are fine tubular structures also organized into large arrays called ______ in the cilia and flagella
axoneme
Function of Microtubules
- Intracellular vesicular transport.
- Movement of cilia and flagella
- Attachment of chromosome to the mitotic spindle
- Cell elongation and movement
- Maintenance of cell shape
actin filaments
composed of actin allow cellular motility and most contractile activity in cells
Microfilaments
Microfilaments function:
- Anchorage and movement of membrane protein
- Formation of the structural core of microvilli
- Locomotion of cells
- Extension of cell processes
rope-like filaments, intermediate in size between microtubules and microfilament
Diameter: averaging 10 nm
Intermediate Filaments
present only in epithelial cells
KERATIN (I and II class)
found in most cells derived from mesenchyme
VIMENTIN (Class III (3))
present in cell body and processes of neurons
NEUROFILAMENT (Class IV (4))
form the nuclear lamina inside the nuclear envelope
LAMINS (Class V (5)
found in almost all muscle cells
DESMINS (Parts of neurofilaments
Glial Fibrillary Acidic Proeteins (GFAP), present in glial cells
GLIAL FILAMENTS(Class III (3))
Beaded filaments (Phakinin and Filensin)
Class 6
cid cytokeratin -> Epidermolysis bullosa
Basic -> keratoderma
Keratin
Desmin myopathy
GFAP (Glial Fibrillary ACidic Protein) - Amyotrophic lateral sclerosis
Kimentin
Charcot- Marie-Tooth Disease
Parkinson’s disease
Neurofilaments
Emery Dreifuss muscular dystrophy
Limb-girdle muscular dystrophy
Lamins
Juvenile onset cataracts
Phakinin (Beaded Fil)
Congenital cataracts
Filesin (beaded fil)
have little or no metabolic activity, but contain accumulated metabolites or other substances not enclosed by membrane
- Fat droplets
- Glycogen granules
- Lipofuscin
- Hemosiderin
Cytoplasmic Inclusions
The region of cells containing the centrioles in periventricular mat.
aka Centrosome
Microtubules Organizing Center
centrosphere or cell center
specialized zone of the cytoplasm containing the centrioles center of activity associated with cell division
Centrosome
called diplosome in nondividing cells
EM: hollow cylinder closed at one end and open at the other
Centrosome
self-duplicating organelles that exhibit continuity form one cell generation to another
Double in number immediately before cell division
Centriole
Prominent in mitosis
Essential for the formation of cilia and flagella
Serve as basal bodies and sites of epithelial cilia
Centriole
long, semi-rigid, helical, hollow tubular structures mostly composed of protein, FLAGELLIN
Show undulating wave type of movement
Flagella
Hair-like processes
Very numerous in:
- Epithelial cells of upper RT
- Parts of female and reproductive tracts
- Ependymal lining the cavities of the CNS
Cilia
contains a blueprint for all cell structures and activities encoded in the DNA of the chromosomes.
It also contains the molecular machinery to replicate its DNA and to synthesize an RNA
Nucleus
Components of the nucleus:
Nuclear envelope
Chromatin
Nucleolus
the disappearance of nuclei due to complete dissolution of DNA by increased activity of DNAsE
Karyolysis
condensation of chromatin leading to shrinkage of the nuclei (they appears as dense basophilic masses)
Pyknosis
fragmentations of nuclei
Karyorrhexis
Selectively permeable membrane that is seven times thicker than plasma membrane and perforated by nuclear pores
Nuclear Envelope
Nuclear Envelope has two eccentric membranes separated by perinuclear space
Outer Nuclear Membrane
Inner Nuclear Membrane
continuous with rER membrane. It has attached polyribosomes
Outer Nuclear Membrane
The inner nuclear membrane is supported by a rigid network of intermediate protein filaments attached to its inner surface called the
nuclear lamina
formed by intermediate filaments that lies adjacent to the inner nuclear membrane
nuclear (fibrous) lamina
contains specific lamin receptors and several lamina-associated proteins that bind to chromosomes and secure the attachment of the nuclear lamina
Nuclear Envelope
a composition of nuclear lamina
lamin
a family of lamina receptors
Emerin
mutation of emerin (X-linked)
associated with mutations in either lamins or lamin receptors.
characterized by early-onset contractures of major tendons, very slow progressive muscle weakness, muscle wasting in the upper and lower limbs, and cardiomyopathy (weakening of the heart muscle).
Emery-Dreifuss muscular dystrophy (EDMD)
mutation of lamin
Autosomal dominant EDMD
In nondividing cells, consists of the DNA and its attendant protein in a largely uncoiled state
In dividing cells, condensed and organized into discrete bodies called chromosomes
Chromatin
two types of chromatin:
HETEROCHROMATIN
EUCHROMATIN
EM: appear as coarse electron-dense material
LM: basophilic clumps
Heterochromatin
dense mass of heterochromatin found in females
Barr bodies
EM: finely dispersed granular material
LM: lightly stained basophilic areas
Euchromatin
The smallest units of chromatin structure are macromolecular complexes of DNA an called
Nucleosome
with much euchromatin and few heterochromatic clumps, more DNA surface is available for transcription
light stained nuclei
rich in highly condensed heterochromatin, tightly coiled DNA is less accessible for transcription
dark-stained nuclei
T/F; Cells with lightly stained nuclei are more active in protein synthesis
True
Each chromosome is formed by two chromatids that are joined together at a point called the
centromere
area located at each end of the chromosome
Shorten with each cell division; studies indicate that telomere length is an important indicator of the lifespan of the cell
Telomere
a spherical, highly basophilic sub domain of nuclei in cells, actively making proteins
It is a non-membranous region of the nucleus that surrounds transcriptionally active rRNA genes It is the primary site of ribosomal production and assembly.
Nucleolus
is the site of ribosomal RNA (rRNA) synthesis and initial ribosomal assembly
varies in size but is particularly well developed in cells active in protein synthesis
Nucleolus
The three morphologically distinct regions of nucleolus:
Fibullar Center
Fibullar Material
Granular Material
contain DNA loops of five different chromosomes (13, 14, 15, 21, and 22) that contain rRNA genes, RNA, Polymerase I, Transcription factors
Fibrillar Center
contain ribosomal genes that are actively undergoing transcription and large amounts of rRNA
Fibrillar material
represents the site of initial ribosomal assembly and contains densely packed preribosomal particles
Granular Material
Newly identified proteins in nucleolus
-> Nucleostemin
Cell division - Cell accumulation
In humans, as in all other multicellular organisms, the rates of cell proliferation and cell death determine the net cell production
Cell Death
disorders of cell accumulation
hyperplasia, cancer, autoimmune diseases
disorders of cell loss
atrophy, degenerative diseases, AIDS, ischemic injury
Two Major Mechanisms of Cell Death
Necrosis
Apoptosis
accidental cell death, is a pathologic process.
It occurs when cells are exposed to an unfavorable physical or chemical environment that causes acute cellular injury and damage to the plasma membrane
Necrosis
(Necrosis) Damage to the plasma membrane may also be initiated by viruses, or proteins called
perforins
Characteristic feature of Necrosis:
Rapid Cell Swelling and Lysis
[Gr., falling off, as petals from flowers] was referred to in the past as programmed cell death
Cellular suicide
Apoptosis
It is characterized by controlled Autodigestion
The cell “dies with dignity” without spilling its contents and damaging its neighbors
Apoptosis
Morphologic and Biochemical Features of Apoptosis:
DNA Fragmentation
Decrease in cell volume
Loss of mitochondrial function
Membrane blebbing
Formation of apoptotic bodies
an irreversible event that commits the cell to die.
a result of Ca2-dependent and Mg2-dependent activation of nuclear endonucleases
DNA Fragmentation
Achieved by shrinking of cytoplasm
cytoskeletal elements become reorganize ribosomes become clumped within the cytoplasm
rER forms a series of concentric whorls, and most of the endocytotic vesicles fuse with the plasma membrane
Decrease in cell volume
Where cytochrome activate the caspase dismantle
caused by changes in the permeability of the mitochondrial membrane channels
Loss of mitochondrial function
results from cell membrane alterations
Membrane blebbing
the final step of apoptosis, results in cell breakage
Formation of apoptotic bodies
