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44 Cards in this Set
- Front
- Back
What does the Endomembrane System consist of?
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Nuclear envelope and perinuclear space
endoplasmic reticulum golgi complex endosomes (anything phagocytosed into a cell) lysosomes transport vesicles |
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What is the Peroxisome and the ER?
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Peroxisome:
-single membrane bound organelle -generation and degradation of H2O2 -contains catalase (destroys H2O2) -detoxification -breakdown of long chain FA -lots in the Liver ER: -has sacs calls cisternae -space between sacs is called lumen -site of biosynthesis of lipids and secreted proteins Smooth: -lack ribosomes -drug detoxification in liver by making them less hydrophobic -hydroxylation (steroid biosynthesis) -transfers electrons from NADH to cytochrome P-450 Rough: -synthesize secretory proteins, lysosomes, and plasma membranes -transitional elements = shuttle lipids and proteins from ER to golgi -site for addition of carbs to glycoproteins, folding of polypeptides, and assembly of multimeric proteins -Protein quality control = ER associated degradation (ERAD), abnormal proteins exported by cytosolic proteosomes |
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What is cytochrome P-450 and P-448?
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P-450:
-activates oxygen for hydroxylation reactions in the smooth ER -enzymes that are activated are called mixed-function oxidases or monooxygenases -example of monooxygenase is elimination of barbiturate drugs P-448: -hydrocarbon hydroxylases -another group of enzymes that catalyze the hydroxylation reaction -metabolize polycyclic hydrocarbons -cigarette smoke is a potent inducer of aryl hydrocarbone hydroxylase |
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What are some specializes functions of the Smooth ER?
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Carbohydrate metabolism:
-in liver cells contains glucose-6-phosphatase which dephosphorylates G-6-P to glucose -without this phosphatase glucose cannot be formed from glycogen Calcium Storage: -Calcium ions pumped into ER by ATP-dependant Ca pumps in SR -ex. SR found in muscle cells |
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What does the Golgi Complex play an important role in and what are its components?
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1. glycosylation of proteins, sorting of proteins for transport to organelles, plasma membrane, or for secretion
2. transition vesicles from ER fuse with cis-Golgi network (CGN) delivering lipids and proteins to golgi complex, eventually goes to Trans-Golgi Network (TGN) Components: -two faces of Golgi stack: cis (facing ER) and trans (tip of TGN cisternae) -Medial cisternae: between CGN and TGN, NAGT1 is concentrated here -stacks are biochemically DISTINCT |
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What are transport and coated vesicles?
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Transport vesicles:
-transport of lipids and proteins coated vesicles: -ER to CGN coated with COP II -CGN to medial coated with COP I -TGN coated with either COP I or clathrin transport vesicles |
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What are the two models that depict the flow of lipids and proteins through the Golgi Complex?
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Stationary Cisternae Model:
-each part of the Golgi stack is a stable structure and traffic is mediated by shuttle vesicles that bud from one cisterna and fuse with another Cisternal Maturation model: -gradually change from CGN to medial to TGN -supported via labelling |
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What are anterograde and retrograde transport?
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anterograde:
-movement from ER through Golgi toward Plasma membrane retrograde: -vesicles from Golgi cisternae to ER |
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What are the stages of the Role of ER and Golgi in Protein Synthesis?
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1st stage:
-start attached to ER in cytosol, then get flipped into lumen = CORE GLYCOSYLATION -Nlinked = Asparagine, Olinked = Serine or Threonine -core structure of carbs consist of two GlcNAc units, 9 mannose, 3 glucose -Protein is NOT HERE YET 2nd stage: -in ER: core oligosaccharide is trimmed, 3 glucose and 1 mannose by glucosidase and mannosidase -in Golgi: further modifications -if no further processing = high mannose oligosaccharide -processing = complex oligosaccharides (ex. galactose, sialic acid, fucose, N-acetyl) -over 200 glycosyl transferases in ER and Golgi Following biosynthesis, glycosylated proteins and liipds face interiors of ER and Golgi |
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What are the steps of Glycosylation and modification of proteins from ER through Golgi?
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In ER:
-biosynthesis of core oligosaccharide for N-linked asparagine residues -processing of core oligosaccharides -ID and removal of misfolded proteins CGN: -attachment of N-acetylgalactosamine to serine or threonine -first step of phosphorylation of lysosomal proteins CGN --> Medial Cisternae -removal of mannose -2nd step of phosphorylation of lysosomal proteins Medial Cisternae: -removal of mannose -attachment to N-acetylglucosamine Medial Cisternae --> TGN -addition of galactose -addition of sialic acid TGN: -addition of sialic acid -attachment of sulfate to tyrosine |
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How does Glycosylation help promote proper protein folding?
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inhibition leads to misfolded proteins
during 2nd stage when glucoses are removed, ER proteins calnexin (membrane bound) or calreticulin (soluble) complex with a glycoprotein and a thiol oxidoreductase (ERp57) to promote disulfide bond formation UGGT then acts as sensor for proper protein folding (quality control), if improper will complex back with calnexin/calreticulin |
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How do membrane lipids mark vesicles?
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tag is phosphate group added to posphatidylinositol (PI)
PI-3 kinase is required inhibition of kinases perturbs vesicle trafficking to the lysosomes |
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What is the trafficking process through the endomembrane system?
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1. Proteins synthesized by ribosomes, initial glycosylation steps occur within ER lumen
2. transition vesicles take new lipids and glycosylated proteins to CGN 3. Lipids and proteins move through golgi stack. At TGN vesicles form either secretory vesicles or endosomes 4. Materials taken in by endocytosis, fuse with early endosomes 5. Unused materials recycled to plasma membrane 6. endosomes become lysosomes 7. retrograde traffic takes stuff back |
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What are Retrieval tags for ER proteins?
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KDEL:
-when protein bound to retrieval tag it goes through conformational change and returns to ER -because acidity lower in ER than CGN protein dissociates -matures in Golgi -KDEL is a ligand for the receptor so becomes bound to be able to come back to ER (retrieval and receptor mediated transport) RESONANT proteins stay in ER, too big for transport and are hydrophobic, therefore dont need to go to Golgi for maturation |
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What are properties of length for golgi complex proteins?
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increase in length of hydrophobic spanning domains from CGN to TGN
membrane thickness increases from ER to plasma membrane |
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How are proteins targeted for lysosomes sorted?
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in ER, N-glycosylation leads to removal of glucose and mannose
in golgi: N-acetylglucosamine-I-phosphate is added to C6 of mannose by the first enzyme, second enzyme removes N-acetyle glucoasmine, leaving the mannose residue Lysosomal enzyme is synthesized and carbohydrate is added mannose is phosphorylated by sequential activity of two enzymes mannose-6-phosphate binds to receptor and tagged enzymes are packaged in clathrin coated transport vesicles pH is lowered, enzyme dissociated from receptor receptors are recycled in vesicles that return to TGN |
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What is I Cell disease?
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mucolipidosis
fibroblasts release lysosomal enzymes extracellularly -defective phosphotransferase leads to lack of mannose-6-phosphate tags -however other pathways exist for targeting lysosomes -in disease RECEPTOR FOR MANNOSE TAG IS EXCRETED |
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What are two Secretory pathways to transport molecules to exterior of cell?
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Constitutive secretion:
-vesicles bud from TGN and move directly to cell surface, process is continuous and independant ex. mucus cells (all the time) Regulated secretion: -vesicles accumulate int he cell then fuse with plasma membrane only in response to extracellular signals ex. Pancreatic insulin cells |
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What happened when a radiolabeled AA added to Rabbit?
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tracer kept building, so there was no secretion due to lack of tags, problem with secretory vesicles
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What happens in Endo, Exo, and phagocytosis?
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Exocytosis:
-calcium triggers exocytosis (activation of kinases) Endocytosis (pinocytosis): -2 ways: non-specific clathrin independant, receptor mediated phagocytosis: -large particles -human phagocytes (neutrophils) -fibroblasts take up collagen to help CT -generate H2O2 to kill microorganisms -takes some microorganism and sends it back to present on MHC for B cells to make antibodies -pseudopod --> phagocytic vacuole --> fuses with early endosome --> forms into a mature lysosome --> digestion occurs |
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What is receptor-mediated endocytosis and transcytosis?
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clathrin dependent endocytosis
-recycling of receptors by change in pH -fuse with vesicles budding from TGN to form early endosomes --> acquire lysosomal proteins to mature into late endosome ex. LDL receptors transcytosis: material in vesicle moves to opposite side of cell and fuses with plasma membrane, releasing material into extracellular space |
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What are Clathrin coated vesicles composed of?
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help with forming vesicles with flat membranes and targeting interactions with cytoskeleton
surrounded by lattices composed of clathrin and adaptor protein (AP), latlice composed of triskelion (heavy and light chains) Adaptor protein - confer specificity and mediate attachment of clathrin clathrin coat drives formation of vesicles from PM to TGN dynamin: GTPase required for coated pit constriction and closing of budding vesicle uncoating ATPase uncoats vesicles after they bud from membrane |
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What is Clathrin independent Endocytosis?
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fluid phase endocytosis
indiscriminate uptake of material primary mechanism of membrane recycling --> controls cell volume and surface area |
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What are the different coats, where are they found, and what are some coat proteins?
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Clathrin: TGN --> Endosomes
Clathrin: Plasma membrane --> endosomes COPI: Golgi complex --> ER or Golgi (retrograde) -fuzzy coat -do NOT bud from ER COPII: ER --> Golgi Caveolin: Plasma membrane --> ? Proteins: ARF: designated ADP ribosylation factor 1, switches GDP for GTP, inserts hydrophobic tail into membrane AP1 and AP2 - designate different adaptor proteins |
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What is the SNARE hypothesis and some examples?
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explaining how membrane vesicles fuse with the proper target membrane
specificity comes from vesicle-SNAREs, target-SNAREs, Rab GTPases and tethering proteins SNAPs mediate fusion, NSF uncouples SNARE after fusion best studied SNARES: -botulism and tetanus |
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What are tethering proteins?
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act over long distances
coiled-coil proteins: -Golgins - needed for initial interaction of COP I and COP II coated vesicles to the Golgi -also connect Golgi cisternae together Multisubunit complexes: -COG -GARP -TRAPP |
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What are properties of Lysosomes?
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cellular digestion:
-degrade all classes of macromolecules -acid hydrolases - keep low pH to help denature macromolecules Endosomes: -early endosomes = TGN + PM -late endosomes have acid hydrolase -final step is activation of hydrolases: by lowering pH, transferring material from late endosome to lysosome |
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What are the two models of transfer from endosomes to lysosomes?
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Transient fusion model:
-late endosome forms temporary connection with lysosome -only new proteins and lipids to be degraded are transferred hybrid model: -late endosome and lysosome fuse, with proteins and lipids not segregated |
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WHat are different types of lysosomes?
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Heterophagic - extracellular origin
Autophagic - intracellular origin phagocytosis and receptor-mediated endocytosis - lysosomes in defense and nutrition residual body - indigestible remain in lysosome, contributes to cellular aging autophagy: macro - structure wrapped in double membrane from ER micro - single membrane extracellular digestion: ex. sperm -rheumatoid arthritis inadvertent release of lysosomal enzymes |
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WHat are some lysosomal storage diseases? What is a peroxisomal disorders?
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Lysosomal:
Gaucher's disease: -glucocerbrosidase defiiciency -macrophages accumulate leading to liver and spleen enlargement Type II glycogenosis (Pompes): -excess glycogen in liver -defective alpha 1,4 glucosidase Hurler and Hunter: -defect in degradation of glycosaminoglycans Tay-Sachs: -missing beta-N-acetylhexosimanse -GM2 Sanfilippo A: -Heparan sulfamidase Niemann- Picks: -Shingomyelinase Krabbe's: -beta galactosidase Peroxisomal: X-linked adrenoleukodystrophy: -defective integral protein responsible for transporting very long chain FA -destroys myelin sheath in CNS Infantile Refsum disease: -phytanic acid leading to build up of unsaturated FA Zellweger's syndrome: -congenital disorder, absence of peroxisomes in liver, kidneys, and brain Neonatal adrenoleukodystraphy: -X-linked (affects boys) -FA accumulate in CNS and destroy myelin sheaths |
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What are some functions of Peroxisomes?
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1. detoxification of harmful compounds
2. oxidation of long chain FA - beta oxidation 3. metabolism of nitrogen-containing compounds - prevents urate crystals which cause gout, catabolizes xenobiotics 4. catabolism of unusual substances 5. breakdown of hydrogen peroxide by catalse 6. urate oxidase breaks down purines (DNA) 7. enzymes for bile acid synthesis |
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How is Hydrogen peroxide metabolized?
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catalytic mode:
-one molecule of hydrogen peroxide is oxidized, 2nd is reduced peroxidatic mode: -electrons derived from organic donor ex. methanol, ethanol etc |
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What are the single-membrane bound organelles?
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lysosome, peroxisome, and vacuoles
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Who are some nobel prize winners and what are they for?
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Gunter Blobel - proteins have intrinsic signals that govern their transport and localization in the cell (physiology)
Mendel - Genetics PCR - Mullis Prions - Prusiner Hunt, Hartwell, Nurse - Cell Cyle |
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What are proteosomes and ubiquitin?
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proteosomes:
-predominant protease in the cytosol ubiquitin: -targets proteins for degradation by proteosomes -small protein chain |
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What is the Ubiquitin-Proteosome pathway?
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Ubiquitin attaches to E1 (taxi)
Ubiquitin is then transferred to E2 E2-Ubiquitin plus E3 bind to a target protein Ubiquitin molecules are attached to lysine residues in target proteins, E2 and E3 detach |
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What are properties of ribosomes?
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40s (small), 60s (large) subunit
40s binds to mRNA and tRNA ands start codon AUG 60s binds to 40s after it finds start codon and has peptidyl transferase activity protein syntheis - translation of mRNA into AA sequence form polysome that is involved in synthesis of cytoplasmic proteins cleave hydrophobic signal sequence by signal peptidase |
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What are properties of CD8 and CD4 T cells and MHCs?
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CD8:
-proteasome pathway -cytosol-derived antigen -intracellular infection (virus) -use granzymes and perforin to kill -MHC I CD4: -lysosomal pathway -Vesicle derived antigen -extracelullar infection (bacteria) -MHC II MHC I - all nucleated cells APC = MHC I and MHC II MHC II deficiency - BARE LYMPHOCYTE SYNDROME |
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What is AIRE?
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Master gene involved in self tolerance of the immune system
Autoimmune polyendocrinopathy: -autoimmune destruction of endocrine glands caused by mutation in autoimmune regulator gene AIRE AIRE is normally expressed in the thymus and serves as a transcription factor in thymic epithelial cells |
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What is EAE?
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Experimental autoimmune encephalomyelitis:
-mouse model of organ specific autoimmune disease mediated by T lymphocytes -model of MULTIPLE SCLEROSIS (destruction of myelin sheath) |
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What are the Hypersensitivity Reactions?
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Type I: immediate hypersensitivity (mast cells and IgE)
Type II: reaction to drugs (penicillin) Type III: Antigen-Antibody complex deposition Type IV: delayed hypersensitivity |
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What are the types of Immunodeficiencies?
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Primary:
-congenital Secondary: -example is HIV (targets CD4) |
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What is hematopoesis?
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development and production of highly differentiated cells from precurso stem cells
cytokines help initiate pluripotent stem cells give rise to all cells found in the blood two lineages - myeloid and lymphoid dendritic are from both lineages |
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What are major APCs?
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dendritic cells (most professional)
macrophages B cells |