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117 Cards in this Set
- Front
- Back
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Down Syndrome |
typical physical characteristics muscle hypotonia and delayed motor skills mental retardation congenital heart disease
detected by karyotyping chromosome 21 trisomy that occurs due to aberrant chromosome sorting in meiosis |
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marfan syndrome |
dominant genetic disorder unique stature- tall with long limbs and fingers defects in heart valves and aortas ocular lens dislocation |
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familial hypercholesterolemia |
common genetic disorder high blood cholesterol and LDL levels development of early onset CV disease
caused by defect in plasma membrane defect in LDL receptor
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Leber's Hereditary Optic neuropathy |
maternally inherited acute loss of central vision in young adults severe optic atrophy
mitochondrial disease: mutations in mtDNA retina= tissue with highest metabolic demand sudden loss in vision in 2nd or 3rd decade |
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duchenne's muscular dystrophy |
x-linked genetic disease awkward movement depressed motor skills muscle wasting muscle contractions muscle fiber deformities |
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epidermolysis bullosa |
group of inherited disorders formation of skin blisters and sores following trivial skin trauma |
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tay-sachs |
autosomal recessive disease cherry red macula poor motor development in infants -unable to sit up, exaggerated startle reflex, child becomes floppy infant mortality
lysosomal storage disease - GM2 ganglisidosis due to mutation in hexosaminidase A (HEXA) gene deficiency, which causes ganglioside accumulation in nerve cells of CNS |
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gaucher's |
autosomal recessive enlarged spleen and liver skeletal disorders severe neurologic complications anemia yellowish-brown skin pigment
lysosomal storage disease mutation in glucocerebrosidase accumulation of lipids within cells and organs (spleen, liver, lungs, kidney, brain) |
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bardet biedl syndrome |
autosomal recessive wide spectrum of phenotypes: polydacytly, retinal degeneration, obesity, renal failure, mental retardation, hypogonadism |
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zellweger syndrome |
congenital disease: lethal within first year of life multiple organs involved: enlarged and malfunctioning liver, lack of muslce tone, glaucoma, mental retardation in utero brain MRI: ventriculomegaly, small cerebral convolutions, periventricular adrenoleukodystorphy
peroxisome disease intracellular transport of peroxisomal proteins defective peroxisome receptor (PXR1) leading to empty peroxisomes
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progeria |
rare disorder of premature aging individuals usually die in teens abnormal growth, skin changes, hair loss small fragile bodies, wrinkled skin, atherosclerosis and CV problems |
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cancer |
malignant neoplasm group of diseases with uncontrolled growth of specific cell type skin melanoma retinoblastoma |
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role of cells in properties of life |
cells grow and divide cells build and degrade molecules and structures cells produce their external environment and respond to changes in their environment, cells change shoe and move, cells sense and send info, cells regulate gene expression to meet changing needs, cells die |
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eukaryotic cell |
plasma membrane membrane bound internal organelles segregation of DNA within defined nucleus cells form complex tissues/ organisms |
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conservation fo genes in evolution |
role of Hox genes in head to tail axis development
role of eyeless (Pax6) in eye development from flys to humans |
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specialized cells form from |
precursor cells |
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generation of specific cell layers leads to |
formation of distinct tissues |
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formation of blood cells |
all different types of blood cells develop form a pluripotent stem cell in the bone marrow |
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dedifferentiation |
cells dedifferentiate from specialized cell: the epithelial to mesenchymal transition (EMT)
often occurs in diseases
cells can dedifferentiate in response to stress or disease
fibroblast dedifferntiation to myofibroblast in scar formation and fibrosis |
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proteins |
bioeffector molecules |
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DNA |
self-replicating blueprints of life |
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RNA |
involved in converting coded info (DNA) into proteins |
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Cell Receptors |
direct activation of enzyme cascades
alteration of gene expression |
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ATP |
captures and transfers energy |
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life cycle of a cell |
cells capable of self-renewal/replication S phase: DNA replication mitosis: cell division and generation of daughter cells G1 and G2: RNA and protein synthesis Go: "waiting" state |
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cell division |
cells must faithfully duplicate their DNA to form daughter cells chromatin condensation and separation during mitosis and meiosis recombination: diversity diseases associated with errors |
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mitosis |
faithful duplication of cell's chromosomes
forms 2 diploid genetically identical daughter cells |
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meiosis |
faithful sorting of each chromosomal pair
crossing over and recombination of sister chromosomes
forms 4 haploid gamete cells (not genetically identical) |
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Retinoblastoma |
due to defects in Rb gene Rb genes normally control cell proliferation by inhibiting transition form G1 to S phase Rb inactivated by cyclin/ CDK phosphorylation |
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Cell death |
the final act of life cell death is important in development
necrosis: cells swell and burst, often associated with inflammation
apoptosis: programmed cell death, requires energy, generation of proteins for self-destruction, avoids release of toxic cell contents |
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cell components / compartments |
plasma membrane intracellular organelles cytoskeleton cytoplasm ECM |
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biomembranes |
lipid bilayer composed of phopholipids and proteins
plasma memranes
intracellular organelles |
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diseases associated with defects in plasma membrane |
familial hypercholesterolemia
cystic fibrosis
retinitis pigmentosa |
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Nucleus |
storage, replication, and transcription of DNA double membrane nuclear membrane (envelope) supported by cytoskeleton (laminas) nuclear pore complexes |
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hutchinson-gilford progeria |
example of laminopathy due to mutation in LMNA (nuclear lamin A)
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lamin |
intermediate filament protein that provides structural support to nuclear envelope |
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secretory pathway |
secreted, membrane, and lysosomal proteins made in ER and Golgi complex secretory vesicles move these proteins to their respective locations |
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Rough ER |
synthesis and post-translational modification of secreted and membrane proteins |
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smooth ER |
steroidogenesis
detoxification reactions |
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ribosomes |
the sites of protein synthesis, where RNA is translated into protein
exist floating freely in the cytoplasm
bound to the Rough ER |
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Golgi |
highly developed in secretory cells and cells exposed to cytotoxins addition of oligosaccharides to proteins and lipids Cis, medial, and trans golgi sorting pathway (lysosomes) exocytosis pathway |
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internal biomembrane environment |
membrane bound channels throughout cytoplasm endoplasmic compartment cytoplasmic compartment secreted proteins do NOT see cytoplasm! |
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Exocytosis |
release of secretory products from cell and renewal of membrane components constitutive exocytosis does not require signal (immunoglobulins) regulated exocytosis requires chemical or electrical signals (secretory granules) vesicle docking and membrane fusion |
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receptor mediated endocytosis |
brings cargo into cells specific receptor recognizes ligand and complex aggregates in coated pit (clathrin) internalization of complex within coated vesicle un-coating of vesicle fusion of endosome with lysosome recycling of free receptor back to plasma membrane |
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lysosomes |
acidic and hydrolytic organelle that degrades variety of biomolecules separates hydrolytic enzymes from cytosol lysosomal membrane proton pump acidifies lumen of lysosome types of lysosomes: primary and secondary pathways: endocytosis, phagocytosis, and autophagy |
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peroxisomes |
small organelles involved in lipid biosynthesis (bile acids, long chain FAs, plasmologens) contain anti-oxidant enzymes (catalase decomposes H2O2) peroxisomal proteins (containing PTS) made in cytoplasm and shuttled to peroxisomes by PTS receptor proteins |
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mitochondria |
powerhouse of cell involved in oxidative phosphorylatoin: krebs, ETC, ATP synthase steroidgenesis and FA oxidation: outer and inner membrane, cristae mitochondrial DNA: encode some mito proteins generation of ROS maternal mitochondrial inheritance role in apoptosis |
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mitochondrial DNA |
small circular DNA mitochondrial proteins also encoded by genomic DNA mitochondrial DNA is maternally inherited |
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Myoclonic epilpsy with ragged red fibers |
Mitochondrial Disease MERRF: defect in mtDNA encoding lysyl tRNA (defective ox-phos complex) generalized muscle weakness and ataxia multiple seizures respiratory and cardiac failure |
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mitochondria and apoptosis |
mito are involved in intrinsic path of apoptosis mitochondrial permeability transition (MPT) pore normally blocked by Bcl-2 increased mitochondrial permeability via opening of MTP release of cytochrome c into cytosol activation of caspases and apoptosome |
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types of biomembranes |
plasma membrane: outer boundary of cells cytomembranes (intracellular): organeller membranes (ER, golgi, mitochondria, lysosomes, peroxisomes, nucleus, vesicles) |
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functions of biomembranes |
structural and functional boundaries of cells and intracellular environments facilitated and active transport energy metabolism maintain chemical and electrical potential cell-cell and cell-matrix adhesion cell-cell recognition cell signaling |
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fluid mosaic model |
membranes = 2D fluids, with proteins embedded into phospholipd bilayer bilayer is viscous, allowing lateral diffusion of lipids and proteins |
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reasons for limited diffusion in cells: |
tight junctions cytoskeletal attachment lipid rafts |
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plasma membrane separates: |
cytosolic and extracellular environments |
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intracellular membranes separate: |
organellar lumen from cytoplasm |
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variation of biomembranes in different cell types: |
smooth flexible membranes of erythrocytes
tufts of cilia from apendymal cells of brain |
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phospholipid bilayer |
-phospholipids are amphipathic -hydrophobic fatty acyl side chains partition inside membrane -hydrophilic head groups interact with aqueous -environment on outside and inside cell -lipid bilayer impermeable to small hydrophilic molecules. |
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biomembrane permeability |
passive diffusion of gases and small hydrophobic and polar molecules
poor diffusion of large polar or charged molecules |
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faces of cellular membranes |
cytosolic face exoplasmic face internal lumen of organelles is topologically equivalent to outside the cell
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this topology is conserved during |
membrane budding/ fusion and protein secretion |
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major classes of biomembrane lipids |
phosphoglycerides
sphingolipids
cholesterol |
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phosphoglycerides |
-the most abundant class of membrane lipids -derivatives of glycerol-3-phosphat conjugated with 2 fatty acyl chains and a polar head group -fatty acyl groups can differ in length and saturation -classified according to the polar head group -plasmalogens |
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plasmalogens |
one of the fatty acyl groups attached to glycerol 1 carbon via ether linkage |
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sphingolipids |
-derived from sphingosine (amino alcohol with long hydrocarbon chain) -long chain FA attached to sphingosine amino group -spingomyelin contains phosphocholine head group -glycosphingolipids |
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glycosphingolipids |
polar head groups are sugars
glycolipids are 2-10% of total plasma membrane lipids
outer surface of plasma membranes |
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cholesterol |
-amphipathic (mostly hydrophobic) 4 ring hydrocarbon -50-90% is present in plasma membranes and associated vesicles -intercalates between membrane phospholipids -precursor for many bioactive compounds (source of steroid hormones) |
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viscosity of lipid bilayer |
100x more viscous than water, the same as olive oil
phase transition between gel-like to liquid state |
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viscosity is regulated by: |
lipid composition FA chain length (longer chain = increased viscosity) FA chain saturation (unsaturation = decreased viscosity) temperature |
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lipid composition influences |
physical properties of membranes
also influences membrane thickness and curvature |
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long fatty acyl chains have |
greater van der Waals interactions compared to short FA chains |
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saturated FA chains are more |
ordered, providing less fluidity compared to unsaturated FAs |
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effect of cholesterol on membrane fluidity |
generaly decreases fluidity by interacting and stabilizing hydrocarbon tails of PLs
orders phospholipid FA chains increasing bilayer thickness |
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thickness of sphingomyelin bilayer |
it is thicker than PC bilayer |
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differences in overall shapes (PC vs PE) can cause |
membrane curving |
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mobility of membrane lipids and proteins |
-phospholipids and sphingolipids rotate along their long axis and move laterally -they do not spontaneously flip flop -specific membrane portents and energy are required for translocation from one leaflet to another -"islands" in membrane leaflets where lateral movement is restricted (i.e lipid rafts) |
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lipid rafts |
-localized region of plasma membrane enriched in cholesterol and sphingolipids -often enriched in specific membrane proteins -participate in cell signaling by concentrating membrane proteins in unique lipid environment |
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lipid composition varies significantly between |
different biomembranes and different tissues |
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differences between ER and golgi membranes |
phospholipids are made in ER
sphingolipids are made in the golgi |
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how does high concentration of sphingolipids affect membrane stability |
increases stability |
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differences in exoplasmic and cytosolic leaflets |
exoplasmic: sphingomyelin -phosphatidylcholine - glycolipids
cytosolic -PE,PS, PI |
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membrane asymmetry |
-cholesterol: in both leaflets, alters membrane fluidity -outside leaflet: glycolipids, sphingomyelin, phophotidylcholine -inside (cytosol) leaflet: negatively charged phospholipids |
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using membrane asymmetry to identify apoptosis |
-phosphotidylserine (PS) located on inner leaflet of plasma membrane -asymmetry is lost when cells undergo apoptosis -annexin V binds PS -use Annexin V bound to fluorescent dye to look for PS on outer leaflet (identify cells undergoing apoptosis) -DARC to identify dying retinal ganglion cells in vivo |
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3 classes of biomembrane proteins |
integral membrane proteins
lipid anchored membrane proteins
peripheral membrane proteins |
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integral membrane proteins |
-embedded in and span phospholipid bilayer -contain transmembrane, cytosolic, and exoplasmic domains -synthesized in RER/golgi
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Transmembrane domain |
- hydrophobic amino aids - single or multiple alpha helix or multiple beta strands
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exoplasmic and cytosolic domains |
-exoplasmic and cytosolic domains: hydrophilic surfaces to interact with aqueous compartments |
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alpha helix domain |
20-25 hydrophobic amino acids side chains interact with lipids coiled-coil dimer |
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integral membrane proteins: single pass transmembrane protein |
-glycophorin A dimer - alpha helix domain -positively charged amino acids bind to phospholipid head groups -extracellular domain glycosylated |
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integral membrane proteins: multipass membrane proteins |
channels and signal transduction GPCRs (7 TM alpha-helices) |
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bacteriorhodopsin |
retinal abdorbs light protein conformational change proton pumped from cytosol hydrogen ion gradient to synthesize ATP
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G protein coupled receptors (GPCRs) |
-large gene family of 7 membrane domain signaling receptors (>1500 genes) -coupled to trimeric G-protein that acts as switch -regulates other membrane bound effector protein for short term signaling -responsible for hormone, neurotransmitter, drug, olfactory, light signaling |
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beta barrel integral membrane proteins |
porins and beta defensins |
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porins |
family of trimeric transmembane proteins
barrel shaped Beta strands forming transmembrane pore |
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beta defensins |
host defense peptides
found in cells of immune system
assist in killing microbes |
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lipid anchored membrane proteins |
protein bound to 1 or more lipids with lipid embedding into phopholipid bilayer
cytosolic face: acylation to N-term Gylcine (v-Src) -prenylation to C-terminal cysteine (Ras) Exoplasmic face: C-terminus coupled to GP phospholids (PI, PE, and suger residues) -example: proteoglycans and Thy.1 |
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asymmetry of transmembrane proteins and glycolipids... asymmetric topology is established... |
during biosynthetic insertion into membrane |
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transmembrane glycoproteins |
only on ectoplasmic surface
carb chains covalently attached to Ser, The, or Asn side chains |
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where is there an abundance of glycoproteins and glycolids |
in plasma membranes of eukaryotes
they interact with ECM, lectins, growth factors, antibodies |
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glycocalyx |
surface of cell has carb coat
-extracellular domain of plasma membrane is glycosylated: membrane proteins, lipids, proteoglycans -functions: protection of cell surface, cell-cell and cell-matrix interactions, leukocyte homing (selectins) |
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defective glycocalyx causes |
cystic fibrosis (airway surface layer)
dry eye (corneal epithelium) |
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example of glycocalyx |
human ABO blood groups |
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peripheral membrane proteins |
bind membrane via interaction with other membrane proteins or with phospholipid head groups
important in binding to ECM and cytoskelton |
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mechanism of action of phospholipase A2 |
positively charges (blue) amino acids bind to negatively charged PL membrane surface
hydrophobic channel for PL with catalytic site that cleaves FA ester |
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extraction of membrane proteins |
peripheral membrane proteins are extracted with high salt concentration
integral and lipid-anchored proteins by detergents
ionic and non-ionic detergents |
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functions of membrane proteins |
cell-cell recognition
cell-cell and cell-matrix adhesion
anchor cytoskeleton to membrane |
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functions of membrane proteins: transport |
facilitated diffusion: driven by electrochemical gradient
active transport: requires energy
transport proteins: carrier proteins, channel proteins (ligand gated and voltage gated) |
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classes of membrane transport proteins |
ATP powered pumps
ion channels
transporters: uniporter, symporter, antiporter |
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membrane function: cell signaling |
-neurotransmitter (NT) is located in synaptic vesicles -nerve impulse cause fusion of vesicles with plasma membrane and release of NT into synaptic cleft -NT binds receptors and opens ligand-gated ion channels on target cell membrane -signaling receptors are often integral membrane proteins ex: TGFB and VEGF signaling |
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Aberrant TGFBeta signaling |
TFGB = transforming growth factor beta
elevated TGFB levels and signaling in disese
fibrotic diseases: -increased ECM deposition - kidney, lung, liver fibrosis -glaucoma |
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glaucoma |
-leading cause of irreversible vision loss -progressive optic neuropathy -elevated IOP = major risk factor
-elevated TGFB in aqueous humor and TM -TGFB increases ECM in aqueous outflow pathway causing elevated IOP -elevated IOP damages optic nerve and kills RGCs |
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Altered Wtn Signaling in Glaucoma |
-Wnt signaling involved in development and cancer -abberant Wnt signaling in glaucoma: elevated levels of Wnt inhibitor sFRP1 -increased sFRP1 elevates IOP -restoring Wnt signaling (GSK3i) lowers IOP |
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phagocytosis |
cells engulf large articles via elaboration of pseudopodium and membrane fusion to form phagosome
phagosome fuses with lysosome (phagolysosome) |
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diseases associated with defective membrane funciton |
muscular dystrophy
cystic fibrosis
retinitis pigmentosa
familial hypercholesterolemia |
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muscular dystrophies |
often fatal muscle weakness and atrophy
duchenne's MD
defects in dystrophin-associated protein complex
complex stabilizes sarcolemma during stress of muscle contraction |
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cystic fibrosis |
-genetic disorder of secretory glands -1/4000 children in US -autosomal recessive -poor growth, execs mucus production -defect in CFTR: chloride ion channel, involved in creating sweat, digestive juices, and mucus |
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retinitis pigmentosa |
group of inherited progressive retinal dystrophies
night blindness precedes loos of peripheral vision
defects photoreptors and/or RPE
multiple genes responsible: Rhodopsin (GPCR) |
