Exam 1: Cell Flashcards
3 Cellular consituents
Organelles
Inclusions
Cytoplasmic matrix (cytosol)
Cytoplasm
part of cell external to nucleus
suspends organelles and inclusions
Cytoplasmic matrix (cytosol)
cytoplasm devoid of organelles and inclusions
Inclusions
nonliving entities found in cytoplasm and nucleus
Stored food, pigments, and crystalline not bound by membrane
Stored foods
Glycogen - abundent in liver and skeletal and cardiac muscle cells
Lipid droplets - found in adipocytes, hepatocytes, muscle, and steroid secreting cells
Glycogen demonstrated by
PAS reaction
McArdle disease
genetic defect in skeletal muscle phosphorylase
Accumulations of glycogen under sarcolemma
Cramping, exercise intolerance, elevated myoglobin, creatine kinase elevated, venous lactate level does not increase with exercise
Exogenous Pigments
Carotene - yellow orange color
Carbon particles
Tattoo pigments - stored in macrophages of dermis
Anthracosis
accumulation of carbon particles in lungs and regional lymph nodes
Harmless
Endogenous pigments
Hemoglobin - cyanosis and myoglobin Hemosiderin Bilirubin Melanin Lipofuscin
Hemosiderin
Iron containing pigment
brown
spleen & liver
Hemosiderosis & Hemochromatosis - accumulation of iron
Melanin
Eumelanin - brown/black found in epidermis
Neuromelanin - found in neurons - substantia nigra
Parkinson’s disease depigmentation
Phaemelanin - red pigment of skin/hair
Plasmalemma (plasma membrane)
separates internal and external environment lipid bilayer (contains phospholipids, glycolipids, cholesterol) Cholesterol strengthens bilayer
Lipid rafts
areas in membrane where sphingolipids and cholesterol concentrated
Thicker
involved in cell signaling
simvastatin
cholesterol inhibitor that induces apoptosis by reduction in raft formation
down regulates cell survival signaling molecule, Akt
Integral proteins
some partially embedded, other extend across entire plasma membrane
Creutzfeldt-Jakob disease
normal prion protein is converted to abnormal variant.
Forms cross-linked filaments - resistant to proteolysis
Functions of proteins
Receptors, transporters, enzymatic control of chemical rxns, linker protein for structural support, cellular identification tags, anchor cell to extracellular matrix, intercellular junctional complexes
Carrier transport proteins
transport one or more chemicals in one direction or two chemicals in opposite direction without direct expenditure of energy
Pump transport proteins
require direct expenditure of energy
Na/K pump
cleaves ATP to transport 3 Na ions out of cell and 2 K ions into cell
regulate intracellular volume
Digoxin
partially inhibits Na/K pump
decrease in Ca/Na transporter = increase in sarcoplasmic Ca ion concentrations - improves cardiac pump performance
Na/K pump and cotransport of glucose and Na
secondary active transport
Na and glucose enter cell as Na moves down its concentration gradient
To maintain gradient Na is pumped out of cell by Na/K pump
Multidrug resistant transporters
primary transporter proteins that are ATPases
MDR-1 expressed in kidney, intestine, liver, and blood-brain barrier - Transports drugs
Overexpression can cause cancer cells to become resistant to cytotoxic drugs
MDR-2 transports conjugated bilirubin
MDR-3 expressed in liver, flippase of phosphatidylcholine
Pores
Aquaporins - channels for water
Vesopressin
causes translocation of aquaporin receptors to plasma membrane of collecting tubule cells
Dystrophin
provides structural ingetrigy
link plasma membrane to underlying cytoskeleton
brown ring
Role of carbohydrates in membrane
attach to lipids and proteins forming glycolipids and glycoproteins, net negative charge repels other negatively charged substances, react with regulatory molecules, play role in cell to cell and cell to matrix recognition, protection
Glycolipids
exclusively on noncytosolic lipid monolayer
Endocytosis
transport into cell
energy ATP and Ca required
Macropinocytosis
Actin-based, nonspecific ingestion
occurs in thyroid cells as they take up thyroglobulin and dendritic cells for immune surveillance
Clathrin-mediated endocytosis
occurs in clathrin coated pits
Dynamin (GTPase) is required to pinch of vesicle
receptor mediated - cholesterol, protein hormones
Phagocytosis
ingestion of large particles (cell eating) mediated by receptors dependent on actin Phagosomes fuse with lysosomes
Exocytosis (bulk secretion)
secretion of cellular synthetic products with secretory vesicles
Secretory vesicles
formed in Golgi complex
fuse with plasma membrane
intracellular trafficking orchestrated by COPs
Consitutive exocytosis
continuous secretory process
secretory product not stored in secretory granules
Regulated exocytosis
secretory product stored in secretory vesicles until signal causes product to be secreted
Porocytosis
quantal release of neurotransmitters
Ribosome
basophilic
small electron dense particles
subunits exported from nucleus to cytoplasm where assemeble when actively synthesizing proteins
Polyribosomes free in cytoplasm
create proteins to be used in cell
Polyriosomes attached to endoplasmic reticulum
create proteins to be secreted
rER
membranous organelle, basophilic
continuous with outer membrane of nuclear envelope
ER stress
accumulation of unfolded/misfolded proteins in ER cisterna
Chaperone synthesis increases, decreased protein synthesis, caspases activated, misfolded proteins tagged for degradation
Targeting signals
sequences of amino acids in protein
direct proteins to their target compartments by binding to receptors specific for the organelles
sER
lacks polyribosomes acidophilic continuous with rER Cisternae more tubular Cholesterol homeostasis, steroid synthesis, phospholipid synthesis, detoxification of drugs, storage & release of Ca in muscle
van Gierke disease
defect in glucose 6 phosphatase or transporter; sER unable to transport glycogen - glycogen accumulation in cytoplasm and nucleus
liver enlargement, hypoglycemia, increased lactate
Cholera toxin gains entry into the cell by using
a glycolipid
Non-coated mediated endocytosis
Cholera and Shiga toxins
Caveolae mediated endocytosis
Simian virus 40
cytochrome p450 and alcohol detoxification takes place in
sER
Synthesis of phospholipids occurs in the lipid monolayer in the
sER and rER
Alastin
involved in shaping the ER
Deficiency leads to fragmented ER & spastic paraplegia
Spastic paraplegia caused by
deficienty in atlastin (ER fragmented)
stiff leg & gait disturbances
Proteasomes
large complex protease
Proteolysis of regulating proteins, damaged proteins, and antigenic proteins (initiate immune response)
Proteasomes are dependent on
ubiquitin for degredation
Abnormal prion proteins inhibit
proteasomes
Defective ubiquination of proteins is implicated in
Parkinson’s disease, as well as a form of cystic fibrosis
Bortezomib
partially inhibits proteasomes
effective against multiple myeloma - promotes apoptosis of cancer cells
Golgi apparatus
Functions as major sorting and distribution center
Proteins packaged into vesicles and moved throughout cell
Golgi apparatus lies between
nucleus and apical cytoplasm
Negative Golgi image
Found in active protein secreting cells
Pale staining of cytoplasm that may be seen in H and E staining
Does not contain ribosomes
Cis, convex, forming face Golgi
face presents towards transitional ER where transport vesicles forming
Transport vesicles carry newly synthesized proteins from ER to Golgi
Trans, concave maturing face Golgi
face opposite of cis
Forms secretory granules (vesicles)
Wilson’s disease
mutation in protein pump for copper in trans-Golgi network of liver cells
Membrane protein-transporting vesicles containing dysferlin
repair microperforations formed in skeletal muscle plasma membranes
Patching is calcium dependent
Mutations in dysferlin
muscular dystrophy
Proinsulinemia
mutated proinsulin missorted into unregulated pathway without prohormone enzyme
Absence of prohormone converting enzyme activity in unregulated pathway
Endosomes
sorting and identifying molecules for recycling or degradation by lysosomes
early, recycling, multivescular, and late
Early and recycling endosomes
cell periphery
pH 6.2 to 6.5
Multivesicular bodies
located between early and late endosomes pH 5 - 6.2 large amounts of membrane and vesicles fuse with late endosomes Secretory role
Late endosomes
located near nucleus
fuse with lysosomes
pH 5
achondroplasia
FGFR3 is recycled instead of degraded, amplifying FGF signaling
abnormal bone growth leads to dwarfism
Lysosomes
acidophilic
enzymes able to digest most biologic molecules
Autophagolysosome (secondary lysosome)
primary lysosome + autophagosome
Macroautophagy - send structures to lysosome
Microautophagy - eliminates proteins and smaller molecules
Chaperone mediated direct transport
Heterophagolysosome (secondary lysosome)
primary lysosome + heterophagosome
Secondary lysosomes
are heterogeneous at EM level (light and dark regions)
Type II Pompe’s disease
Glycogen accumulation in lysosome
alpha-1,4-Glucosidase deficiency
Clathrin
used in endocytosis and at Golgi to create secretory vesicles
COPII
anterograde transport from ER to cis Golgi network
COPI
retrograde transport from cis Golgi network to ER
needed to return membrane, vSNARE proteins, and missorted ER proteins back to ER
SNARE proteins
allow vesicle to recognize its target domain and dock
vesicle SNARES - on vesicle
Target SNARES on target membrane
Neurotoxins of tetanus and botulism
enter nerve terminals and proteolyse SNARE proteins
prevent neurotransmitter vesicles from docking with nerve cell membrane and releasing neurotransmitter
Braking effect on motoneurons = paralysis
Mitochondria
Acidophilic
Pleomorphic - change shape
Located in areas of high metabolic activity - increase in skeletal and cardiac muscle
Outer mitochondrial membrane
permeable
large channel forming proteins (porins)
Translocator protein
Inner mitochondrial membrane
selectively permeable
high concentration of phospholipid cardiolipin
enzymes for ETS
Tubular Cristae
steroid-secreting cells
synthesize steroid hormones
Cristae in cardiac and muscle cells
shelf like
Mitochondrial matrix contains
Enzymes of Kreb cycle
Enzymes for fatty acid beta oxidation
Matrix granules
Mutations in mitochondrial DNA are implicated in
diabetes, deafness, heart disease, Alzheimers, Parkinson, LHON
MERRF (myoclonic epilepsy with ragged red bifers)
red appearing mitochondria seen with Gomori trichrome stain
at EM - parking lot inclusions
myoclonus, seizures, ataxia
Peroxisomes
contain oxidative enzymes
enzymatically forms water and oxygen from hydrogen peroxide
enzymes for beta-oxidation of fatty acids
ingested ethanol oxidation
synthesis of plasmalogens
Zellweger syndrome
peroxisomal enzymes not transported into peroxisome - defective import protein on unit membrane of peroxisome
Import of peroxisomal proteins
Enzymes formed by free polyribosomes in cytoplasm, then transported into organelle
Phospholipid exchange proteins move phospholipids from ER membrane to peroxisomal membrane
Antilipidemics
increased uptake of triglycerides and cholesterol by hepatic cells
Ramps up beta oxidation of fatty acids by mitochondria nd peroxisomes - peroxisomes increase in number
Defects in synthesis of plasmalogens lead to
abnormalities in myelination of nerve cells
Cytoskeleton
made of microtubules, microfilaments, thick filaments, & intermediate filaments
Microtubules
13 longitudinally arranged protofilaments made of tubulin dimers
Colchicine, vinblastine, and vincristine
inhibit polymerization of microtubules
Taxol
inhibits depolymerization of microtubules
Microtubules function to
support cytoplasm and organelle, cell division, motility of cilia and flagella, long-range transport of vesicles
Kinesin
transport vesicles toward periphery (negative to positive)
Defect in kinesin
decrease in transport of serotonin receptors - development of anxiety disorders
Dynein
transport vesicles toward nucleus (positive to negative)
Microtubule-associated proteins (MAPS)
stabilize microtubules
Alzheimer’s results from
hyperphosphorylation of tau - leads to tangles
Microfilaments
comprised of actin;
structural support, core of microvilli and stereocilia, movement, cytokinesis, formation of filopodia
Cytochalasin B
prevents polymerization of actin - affects microfilaments
Thick filaments
comprised of protein myosin;
mutation in gene coding for mysoin causes severe form of cardiomyopathy
Intermediate filaments
Cytokeratin, Desmin, Vimentin, Neurofilaments, Glial fibrillary acidic protiens, Nuclear lamins
Cytokeratin
in epithelial cells
forms tonofilaments
Mallory bodies - characteristic of alocholic liver disease
Epidermolysis bullosa simplex - skin becomes fragile and damaged
Desmin
found in striated muscle and nonvascular smooth muscle
mutations involve cardiac and skeletal myopathies
Vimentin
fibroblasts and chondroblasts
Neurofilaments
most nerve cells, mutations associated with neuropathies
Glial fibrillary acidic proteins (GFAP)
astrocytes Alexander disease (degenerative disease of brain white matter), astrocytomas, chronic gliosis have aggregates of GFAP
Function of Intermediate Filaments
structural support
Centrosome
Microtubule-organizing Center (MTOC)
Specialized region near nucleus containing two centrioles
conductor of microtubule
Centrioles
perpendicular to one another
microtubules arranged in 9x3
form mitotic spindle
Nucleus
one per cell usually
Basophilic
Nuclear envelope, nuclear matrix, chromatin, nuclear bodies
Cajal bodies
modifying and assembling molecules needed to splice pre-mRNA into mRNA
include snRNA, snoRNA, snRNPs
Spinal muscular atrophy
muscle wasting
defective SMN protein localized to GEMS (resemble Cajal bodies)
death of motor neurons in gray horns of spinal cord
Interchromatin granule clusters (speckles)
storage depots of snRNAs and proteins
can become engaged in pre-mRNA splicing
Promyelocytic leukemia (PML) bodies
modify and assembeling proteins involved in DNA repair and triggering apoptosis
Nuclear (fibrous) lamina
support inner membrane
Disassembly of nuclear envelope during prometaphase - lamins phosphorylated
Reassembly of nuclear envelope during telophase - lamins dephosphorylated
Heterochromatin
coiled
transcriptionally inactive
Barr body - inactiated X chromosome in female
Euchromatin
uncoiled
Synthetically active
Nucleolus
not membrane bound
rich in rRNA and protein
3 components: Nucleolar-organizer DNA, Pars fibrosa, Pars granulosa
Nucleolar-organizer DNA
contains sequence of bases that code for transcription of rRNA
Pars fibrosa
Newly transcribed rRNA just beginning to become complexed with proteins
Pars granulosa
Maturing subunits of ribosomes
G1 (interphase)
replication of centrioles begins
Checkpoints for G1 DNA-damage
Restriction - point of no return
S (synthesis) of interphase
DNA synthesis can occur
S DNA damage checkpoint
G2 (interphase)
accumulate ATP for mitosis synthesis of tubulin to form microtubules centriole replication complete Checkpoints: Unreplicated DNA G2 DNA damage
G0
nondividing cells
Striated muscle, most neurons
Prophase
chromatids condensed
centriolar pairs migrate to opposite ends of cell
Prometaphase
nuclear envelope starts to disappear
Metaphase
chromatids line up at equator of cell
Colchicine will arrest dividing cells at metaphase
Anaphase
chromatids separate
Telophase
nuclear envelope reforms
M phase checkpoints
Spindle assembly
chromosome segregation
Telomerase
maintains length of telomere sustaining capacity of cell to divide - expressed in most tumor cells & germinal cells
Apoptosis
programmed cell death
Phosphatidylserine - translocated to extracellular monolayer - marks cell as dead
Extrinsic pathway
Fas ligand and Fas receptor
Adaptor protein
caspase-8
Intrinsic pathway
cell injury causes release of cytochrome c
activated caspase-9
FasL counterattack
tumor cells evade immune attack by expressing FasL - destroy immune cells by triggering their elimination via apoptosis
Estrogen
anti-apoptotic effect on osteoblasts
