cellular Flashcards
Cell cycle phases are regulated by what?
cyclins, CDKs, tumor suppressors
how do CDKs regulate cell cycle?
cyclin dependent kinases that are constitutive and inactive
how do cyclins regulate cell cycle?
regulatory proteins that control cell cycle events;
phase specific;
activate CDKs
what must be both activated and inactivated for cell cycle to progress?
cyclin-CDK complexes
What are primary tumor suppressors and where is there primary action?
p53 and hypophosphorylated Rb normally inhibit G1 to S progression
what are the 3 different types of cell types? define where each is prevented in cell cycle
permanent: G0 and regenerate stem cells;
stable: enter G1 & G0 when stimulated;
labile: never go G0 & divide rapidly w/ short G1
what are the permanent cells?
neurons, skeletal, cardiac muscle, RBCs
what are the stable cells?
hepatocytes, lymphocytes
what are the labile cells?
bone marrow, gut epithelium, skin, hair follicle, germ cells
what is important of rough ER?
site of synthesis of secretory (exported) proteins and N-linked oligosaccharide addition to many proteins
What are the rER in neurons? what is their role?
Nissl bodies synthesize enzymes ChAT makes ACh and peptide neurotransmitters
what is the importance for free ribosomes?
unattaches to any membrane; site of synthesis of cytosolic and organellar proteins
what specific cells are rich in rER?
mucus-secreting goblet cells of small intestine and Ab secreting plasma cells
What is important for smooth ER?
site of steroid synthesis and detox of drugs and poisons
what cells are rich in smooth ER?
liver hepatocytes and steroid hormone-producing cells of adrenal cortex are rich in sER
importance of Golgi
distribution center for proteins and lipids from ER to vesicle and plasma membrane;
modifies N-oligosaccharide on asparagine;
adds O-sugar on serine and threonine;
adds mannose-6-phosphate to proteins for trafficking to lysosomes
What are endosomes used for?
sorting material from outside cell or from Golgi to send it back to lysosomes for destruction or Golgi/membrane for use
What is I cell disease?
inherited lysosomal storage disease;
failure of addition of mannose-6-phosphate to lysosome proteins=> enzymes secreted outside cell instead of targeted to lysosome
How will I cell disease present?
often fatal in childhood coarse facial features; clouded corneas; restricted joint movement; high plasma levels of lysosomal enzymes
What are the vesicular trafficking proteins? and their actions
COP I: Golgi->Golgi (retrograde); Golgi->ER
COP II: Golgi->Golgi (anterograde); ER->Golgi
Clathrin: trans-Golgi->lysosomes;
plasma membrane->endosomes (receptor mediated endocytosis)
what is peroxisome
membrane-enclosed organelle involved in catabolism of very long fatty acids and amino acids
what is proteasome
barrell shaped protein complex that degrades damaged or unnecessary proteins tagged for destruction w/ ubiquitin
what are the drugs that act on microtubules?
Mebendazole/thiabendazole=> antihelminthic; Griseofulvin=> antifungal vincristine/vinblastine => anti-cancer paclitaxel=> anti-breast cancer colchicine=> anti-gout
what is the structure of microtubules?
cylindrical structure composed of a helical array of polymerized dimers of alpha and Beta tubulin
What binds the dimers of microtubule?
2 GTP bound
Where are microtubles associated with?
flagella, cilia, mitotic spindles;
involved in slow axoplasmic transport in neurons
what are the molecular motor proteins of the cell? and how they moved
dynein=> retrograde to microtubule from (+) -> (-)
kinesin=> anterograde to microtubule (-) -> (+)
What causes Chediak Higashi syndrome?
mutation in lysosomal trafficking regulator gene (LYST) that is required for Mt dependent sorting of endosomal proteins into late multivesicular endosomes
what is the result of a mutation in lysosomal trafficking regulator gene?
recurrent pyoenic infections;
partial albinism;
peripheral neuropathy
How is a cilia arranged?
9+2 arrangement of Mt
for cilia to to bend, what must be present?
axonemal dynein=> ATPase links peripheral 9 doublets and causes bending of cilium by differential sliding of doublets
What causes Kartagener’s syndrome?
immotile cilia due to dynein arm defect
what are the results of kartagener’s syndrome
male infertility (immotile sperm) and decrease in female fertility;
bronchiectasis;
recurrent sinusitis (bacteria, particles not pushed out);
assoc w/ situs inversus
What are actin and myosin found in cytoskeleton?
microvilli, muscle contraction, cytokinesis, adherens junctions
What are microtubules used for?
movement;
cilia, flagella, mitotic spindle, axonal trafficking, centrioles
What are intermediate filaments used for?
structure;
vimentin, desmin, cytokeratin, lamins,
glial fibrillary acid proteins, neurofilaments
What is the composition of the plasma membrane?
asymmetric lipid bilayer;
contains cholesterol, phospholipids, sphingolipids, glycolipids, proteins
Give stain and what cell type for different intermediate filaments
vimentin=> connective tissue; desmin=> muscle; cytokeratin=>epithelial cells; GFAP=> neuroglia; neurofilaments=> neurons
where are Na/K ATPase located?
cytosolic side
How does ouabain work?
inhibits by binding to K+ site
what types of drugs inhibit Na/K ATPase?
cardiac glycosides => digoxin and digitoxin
How do cardiac glycosides (digoxin and digitoxin) help the heart?
inhibit Na/K ATPase leading to direct inhibition of Na/Ca exchange to increase intracellular Ca causing increase in cardiac contractility
what is significant about collagen use in the body?
organizes and strengthens ECM => extensively modified by post-translational modification
What is the most common type of collagen?
Collagen I: bone, skin, tendon => dentin, fascia, cornea, late wound repair
defect in type I collagen results in what disease
osteogenesis imperfecta
where is type II collagen found?
cartilage (including hyaline), vitreous body, nucleus pulposus
Where is type III collagen found?
reticulin=> skin, blood vessels, uterus, fetal tissue, granulation tissue
defect in type III collagen causes what?
Ehlers-Danlos
what does type IV collagen make up?
basement membrane or basal lamina
defect in type IV collagen causes what?
Alport syndrome
What are the steps to collagen synthesis both inside and outside the fibroblasts?
inside: synthesis (RER); hydroxylation (ER); Glycosylation (ER); exocytosis;
outside:
proteolytic processing;
cross-linking
inside the fibroblasts, what occurs in first step of collagen synthesis?
Synthesis:
translation of collagen alpha chains
(preprocollagen)-usually Gly-X-Y
=> X & Y are proline or lysine
what occurs in step 2 of collagen synthesis?
hydroxylation:
hydroxylation of specific proline and lysine residues => requires vitamin C
what is the deficiency that leads to scurvy?
vitamin C
what is the 3rd step of collagen synthesis?
Glycosylation of pro-alpha chain hydroxylysine residues & formation of procollagen via H+ and disulfide bonds => triple helix of 3 collagen alpha chains
If problems forming the triple helix occur in glycosylation, what disease is associated?
osteogenesis imperfecta
what is the 4th step of collagen synthesis?
Exocytosis of procollagen into extracellular space
outside of the cell, what is the 5th step of collagen synthesis?
proteolytic processing:
cleavage of disulfide rich terminal regions of procollagen, transforming it into insoluble tropocollagen
what is the last step of collagen synthesis?
cross-linking:
reinforcement of many staggered tropocollagen molecules by covalent lysine-hydroxylysine cross-linkage (Cu contains lysyl oxidase) to make collagen fibrils
What disease is associated with problems in cross-linking?
Ehlers-Danlos
genetic bone disorder (brittle bone disease) caused by variety of gene defects?
osteogenesis imperfecta=> autosomal dominant w/ abnormal type I collagen
What does the most common form of osteogenesis imperfecta cause?
- multiple Fx w/ minimal trauma; may be in birth
- blue sclerae due to translucency of connectiv tissue over choroidal veins
- hearing loss (abnormal middle ear bones)
- dental imperfections due to lack of dentin
define ehlers-danlos syndrome
faulty collagen synthesis causing hyperextensible skin,
tendency to bleed (easy bruising);
hypermobile joints
There are 6 types of ehlers danlos syndrome. what are they typically associated with?
autosomal dominant or recessive
joint dislocation;
berry aneurysms;
organ rupture
in severe, classic Ehlers-Danlos, what type of collagen is affected?
Type I or Type V collagen
What type of collagen is associated w/ Alport syndrome?
XLR=> due to a variety of gene defects resulting in abnormal type IV collagen
what is alport syndrome characterized?
progressive hereditary nephritis and deafness;
ocular disturbances
Type IV collagen is important structurally in what areas?
basement membrane of kidney, ears, and eyes
where is elastin typically found?
stretchy protein w/in skin, lungs, large arteries, elastic ligaments, vocal cords, ligamenta flava
What is the ligamenta flava?
connects vertebrae => relaxes & stretched conformations
What are amino acids found in elastin?
nonhydroxylated forms that are rich in proline and glycine
what is the role in tropoelastin?
fibrillin scaffolding
What gives elastin its elastic properties?
cross-linking extracellularly
What breaks down elastin? what inhibits this breakdown?
elastase;
inhibited by alpha-1-antitrypsin
what is a defect in fibrillin lead to?
Marfan’s syndrome
What does an alpha-1-antitrypsin deficiency cause? what is it a result of?
emphysema => results in excess elastase activity
What are wrinkles of aging due to?
reduced collagen and elastin production
