Review exam 2020 Flashcards
interermediate filament protein that are responsible for connecting chromatin to the nuclear membrane.
Lamin
During interphase, when the nuclear envelope is intact, lamins are in the _____ state
dephosphorylated
Early in mitosis, lamins are _____ by a kinase causing the chromatin-nuclear membrane connection to _____, thus beginning the process of nuclear membrane disassembly and chromosome condensation.
phosphorylated
disassemble
Late in mitosis, a ______ returns lamins to the ______ state, thus permitting nuclear membrane assembly and chromosome decondensation to occur.
phosphatase
dephosphorylated
Laminopathies (2)
progeria
Restrictive dermatopathy
Problem in progeria
lamin is hyperphosphorilated
Nuclear transport disease
Huntington’s Disease
SINES
block action of exporting
Exportins. Specific function of exporting 1
export stuff out of nucleus. Exportin 1 exports tumor suppressors.
Signal recognized by exportin
Nuclear Export signal
What cells overexposes exporting-1?
Cancer cells
Signal required for import into nucleus
Nuclear localization signal
Cargo smaller than 5-10kd enter nucleus via ____ through nuclear pores. Larger cargo is actively transported through nuclear pores and guided by ____
diffusion
chaperones
Nucelar mechanism of why Huntington’s happens
The mutant huntintin protein is susceptible to proteolysis, and small (<5kD) fragments of the mutant protein ends up in the nucleus because they are able to diffuse through the nuclear pores.
Membranes are bout ___% lipid, ___% protein and _____ amount of carb.
50,50, small
4 classes of membrane lipids (in order of abundance)
Phospholipids
Sphingolipids
Cholesterol
Eicosanoids
Lipids are ______ distributed in the membrane. Outer leaflet more ____ than inner leaflet
asymmetrically
3 eicosanoid
Prostaglandins
Tromboxanes
Leukotrienes
Function of prostaglandins (eicosanoid)
regulation of vascular tone, smooth muscle contractility, and uterine contraction
Function of Tromboxanes (eicosanoid)
induces platelet aggregation
Function of Leukotrienes
induce vasodilation and bronchoconstriction in asthma and anaphylaxis
Two key properties of Membrane lipids
Fusogenicity and fluidity
HIV and Measles take advantage of ____ property of phospholipids
fusogenic
Contrary to phospholipids, sphingolipids have no _____ properties
fusogenic
Kinky, (fusogenic) property of phospholipid can lead to _____
disease
3 diseases resulting from sphingolipid metabolism (aka Lysosomal storage diseases), and what is unique about these diseases
Tay-Sach’s (prevalent in certain ethnic groups)
Gaucher (first to be treated successfully with recombinant enzyme replacement therapy)
Fabry (same as Gaucher)
Factors affecting membrane fluidity
4
- Double Bonds
- Acyl chain length
- Temperature
- Cholesterol (more cool=more fluid)
Mechanism of mycoplasma
The mycoplasma attach to the base of respiratory epithelial cell cilia and extract the cholesterol from the membrane surrounding the cilia to use for their own metabolic purposes. Removing the cholesterol results in a much more fluid membrane that does not permit the cilia to move rhythmically, or “beat”. Mucous cannot be moved out of the respiratory tract and the mycoplasma are thus able to proliferate, leading to pneumonia.
Sphingolipid-rich Microenvironments
in the Membrane That Move Rapidly Within a Leaflet. Are major functional organizers of the membrane, bringing lipids and proteins together.
Lipid rafts
Lipid rafts are critical for (3)
1) concentrating ligand-receptor complexes into coated pit regions of the Plasma Membrane for Receptor mediated endocytosis
2) important in bringing together the components of signal transduction pathways
3) mobilizing matrix-modifying enzymes at the leading edge of migrating cells
Functions of carbohydrates in cell surface
1) blood-type antigens
2) pathogen recognition sites
3) reservoir for cytokines/growth factors
the role of the carbohydrates on membrane glycoproteins in determining blood types
self-recognition
interaction of coccidial parasites with cell surface carbohydrates
coccidiosis
toxoplasmosis is a type of ______, transmitted via ______, and can cause severe ________
coccidiosis, transmitted via cat feces, and can cause severe birth defects
if it’s a bacteria or bigger it gets into cells via _______
phagocytosis
if it’s a virus or smaller it goes into cells via _______
Receptor mediated endocytosis
proteins called _____ are involved in concentrating ligand-receptor complexes into specialized regions of the membrane called ________ pits.
Clathrin, clathrin-coated pits
______ are often used to ferry the ligand-receptor complexes to the coated pits
Lipid rafts
The _______ becomes activated in the membrane of endocytic vesicles, thus lowering the pH of the vesicle interior.
H+-ATPase
Phagocytosis is an ______-based process.
actin
Basically, _______ receptors on the plasma membrane recognize IgGs that have coated the particle to be ingested via phagocytosis
Fc
Important diseases that involve altered transport (11)
Cystic Fibrosis (chloride anion transport via the CFTR, an ABC-class ATPase transporter)
infantile hypoglycemia
drug resistance in cancer chemotherapy
Familial Hypercholesterolemia rabies influenza Legionnaire Disease streptococcal infections Leishmania tuberculosis leprosy Tangier Diseae
Cause of Cystic Fibrosis
chloride anion transport via the CFTR, an ABC-class ATPase transporter
Cause of infantile hypoglycemia
ABC-type ATPase
Cause of drug resistance in cancer chemotherapy
ABC-type ATPase
Cause of Familial Hypercholesterolemia
receptor-mediated endocytosis and due to a defect in the LDL receptor
Cause of rabies
receptor-mediated endocytosis
Cause of influenza
receptor-mediated endocytosis
Cause of Legionnaire Disease
streptococcal infections
Cause of Leishmania
phagocytosis
Cause of tuberculosis
phagocytosis
Cause of leprosy
phagocytosis
Symptoms of Tangier Disease
coronary heart disease (CHD)
neurological problems
swollen, bright orange tonsils
Implications of studying Tangier Disease
Revealed process of reverse cholesterol transport (i.e., how cholesterol gets out of cells).
Profound implications and understanding of CHD.Analyzing the genome of affected individuals enabled researchers to first determine which chromosome was involved, and then to isolate the Tangier gene. When the Tangier gene was sequenced, it turned out to be a member of the ATP-Binding Cassette (ABC) family of transporters.
Most striking biochemical change in Tangier disease patients is markedly reduced ________.
of High Density Lipoprotein (HDL; also known popularly as “good cholesterol”).
Biochemical pathway of Tangier Disease
If the Tangier ABC transporter is
defective, cholesterol is not transported out of the cells into the plasma and this causes the “empty” HDL to be cleared from the plasma into lymph glands, thus explaining the reduced HDL levels in the plasma and the buildup of cholesterol in the blood vessel wall
Low levels of ____ are found in 55% of Coronary Heart Disease Patients
HDL (High density lipoproteins)
the first 20-25 aa translated of a protein determine if _____
if the protein continues to be translated in the cytoplasm or contains the hydrophobic “Signal Peptide” that will cause the ribosome/nascent protein complex to relocate to the ER to finish translation of the protei
Possible Fates of Proteins Translated in Cytosol
- Nucleus
- Mitochondria
- Cytoplasm
- Peroxisomes
Possible Fates of Proteins Translated in ER
- ER
- Plasma membrane
- Secretory Vesicles
- Lysosomes
- Golgi
Diseases of Peroxisomal Targeting (2)
- Neonatal Adrenoleukodystrophy
2. Zellweger Syndrome
Diseases of Nuclear Targeting (1)
Huntington
Lysosome Storage Diseases (4)
- Gaucher,
- Fabry
- Tay-Sachs
- Mucopolyasaccharide
Several LSDs (lysosomal storage disease) are now being treated with either _________ or ______ therapies
enzyme replacement or enzyme enhancement therapies.
______ is the tripeptide sequence that targets proteins to the peroxisome
S-K-L
short (typically 5-6) basic aa sequences are the _________
Nuclear Localization Signals (NLS)
3) a long-ish (about 75 aa) sequence near the N-terminal end of the protein directs proteins to ________
mitochondria
defects in KDEL lead to _______
dilated cardiomyopathies
Subunit of Microtubules
tubulin
Subunit of microfilaments
actin
Subunit of intermediate filament (6)
- lamins
- keratin
- desmin
- neurofilamin
- vimentin
- GFAP
Accessory proteins of microtubules
Tau
Hyperstable structures of microtubules (2)
- axonemes (cilia and flagella)
2. centrioles
Hyperstable structures of microfilaments (2)
- sarcomere (muscle)
2. microvilli
Hyperstable structures of intermediate filaments
- desmosome
2. hemi-desmosome
Motors of microtubules
- dynein (retrograde)
2. kinesin (orthograde)
motor of microfilament
myosin
motor of intermediate filament
None
Functions of microtubules
- cilia/flagella functions
- mitotic spindle
- organelle/cargo transport
functions of microfilaments
- phagocytosis
- cytokinesis
- cell motility
Function of intermediate filaments
mechanical integrity
Drugs for microtubules
- taxol
2. vinca alkaloids (colchicine, vinblastine)
Medical significance of microtubules (diseases) (2)
- Kartageners (Primary Ciliary Dyskinesia, Immotile Cilia Syndrome)
- cancer chemotherapy dementias (Tau-opathies)
Medical significance of microfilaments (3)
- Hereditary Spherocytosis
- Listeria infection
- Smallpox/Vaccinia
Medical significance of intermediate filaments
- laminopathies
- blistering diseases
- cancer diagnosis
Viruses ______, _____, and bacterium _____ are special examples of pathogens that hijack the actin machinery of the host cell to propel themselves from one cell into another without being exposed to the immune system
Viruses smallpox and vaccinia
Bacterium Listeria
Problem in Kartageners syndrome
microtubules are lacking cilia
An increase in the size or volume of a cell. Not an altered proliferative state. Examples include muscle cells of a bodybuilder, adipose cells during fat accumulation, oocytes during maturation.
Hypertrophy
Irreversible proliferation: proliferation continues in the absence of an external stimulus.
Neoplasia
Regeneration
1-for-1 replacement of lost cells by the same cell type
e.g. Endothelial cell regeneration following vascular surgery; liver cell regeneration following partial hepatectomy or live-donor liver transplants (in the donor, not the recipient).
Hyperplasia
increase in the number of cells in a tissue; cells are fully differentiated. Can be physiological (helpful) or pathological (harmful).
e.g. Hematopoietic cells in bone marrow following severe blood loss or changes in altitude (helpful); thyroid cells in Grave’s Disease (hyperthyroidism; harmful); smooth muscle cells in the arterial wall in atherosclerosis or following vascular surgery (termed restenosis; occurs following angioplasty, coronary artery bypass graft, arterio-venous shunts, etc.; harmful)
Metaplasia
adaptive substitution of one cell type for another
e.g. Replacement of ciliated columnar epithelium by stratified squamous epithelium in response to chronic inflammation (e.g., chronic PID) or other injurious stimuli (e.g., smoking).
Dysplasia and 2 examples
activated metabolic pathways for proliferation; loss of orientation in a tissue. Abnormal appearance (pleiotropy, disorientation within tissue, high mitotic rate) of cells
examples:
- Pap Smear in women
dysplastic moles removed from skin
2 Types of Neoplasia (and examples)
Benign –loss of proliferation control only; “benign” tumors, like fibroids
Malignant – loss of both proliferation and positional controls; metastatic tumors; “cancer”
Regeneration, Hyperplasia, Metaplasia and Dysplasia
Altered proliferative states of cells that are reversible (or at least stoppable): proliferation stops when the stimulus that provoked it is removed.
3 steps of apoptosis
- Induction
- Modulation
- Execution
3 categories of apoptosis inducers
Physiologic, damage related, therapy associated
2 major pathways of apoptosis induction
Intrinsic and extrinsic
Modulation of apoptosis only happens in ____induction pathway and is done by ____proteins
intrinsic, Bcl proteins
Execution of apoptosis is done by ___A__ followed by ___B___. ___A___ are directly responsible for blebbing
Caspases (particularly Caspase-3), followed by endonuclease.
Caspase 3 is responsible for blebbing
Physiologic inducers of Apoptosis
- TNF-alpha
- FasL
- growth/survival factor withdrawal
- glucocorticoids
Damage-related inducers of Apoptosis
- Viral infection
- Heat shock
- Toxins
- Tumor suppressors
- Oxidants/free radicals
Therapy associated inducers of apoptosis
- UV/gamma radiation
2. chemotherapeutic drugs
_____ reduce neuronal damage after stroke
Apoptosis inhibitors
During apoptosis, caspases activate specific endonucleases that cleavecleave the DNA in the ______ between the nucleosomes
the linker regions between the nucleosomes
Dysregulated apoptosis—either too much or too little—is the hallmark of 5 conditions:
- Syndactyly and polydactyly
- Expansion of many cancers
- The cachexia (“wasting”) seen in some late-stage cancer patients
- Polycystic Kidney Disease
- Hashimoto’s (autoimmune form of hypothyroidism)
Clinical Significance of Cell Birth and Death
- Liver regeneration following partial hepatectomy
- Restenosis following vascular surgery
- Grave’s Disease (hyperthyroidism)
- Bone marrow replenishment following blood loss
- Chronic pelvic inflammatory disease
- Pulmonary function in smokers
- Pap smear
- Fibroids
- Cancer
- Polydactyly and Syndactty
- Polycystic Kidney Disease
- Hashimoto’s (hypothyroidism)
- Burkitt’s Lymphoma
Hashimoto Disease
Most common form of hypothyroidism. Represents too much apoptosis in thyroid gland.
Intrinsic (mitochondrial) pathway of apoptosis
Withdrawal of growth factors, hormones —->stimulates mitochondria membrane modulation of apoptosis (by Bcl-2)–>mitochondrial leakage of cytochrome-c, that initiates caspase cascade–> initiator caspases are activated–> activator caspases activted–> 1) endonuclease activation (degrades DNA)and breakdown of cytoskeleton
Therapeutic uses of apoptosis (2, first has 2 specific conditions second has 3 specific diseased)
- may be useful in limiting the damage caused by strokes or heart attacks
- Other diseases or pathologies in which modulating apoptosis is a potential therapy include cancer, restenosis following vascular surgery, and autoimmune diseases like Hashimoto’s
Extrinsic (death receptor-initiated) pathway
Receptor-ligand interactions (FAS & TNF receptor)–> Adapter proteins activated–>initiator caspases activated–>activator caspases activted–> 1) endonuclease activation (degrades DNA)and breakdown of cytoskeleton
