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2.24.2010 2.24.2010 Document Transcript

  • 2.24.2010<br />
    • Smooth ER
    • Lipid, Steroids, cholesterol synthesis
    • Ca2+ storage
    • Breakdown of glycogen into glucose
    • Detoxification of alcohol and drugs via hydroxylation
    • Endomembrane System
    • Movement can occur anterograde and retrograde
    • Rough ER
    • Lipid synthesis
    • Rough = ribosomes studded on the membrane of the ER
    • Important for synthesizing proteins.
    • All endomembrane proteins, secreted proteins, plasma membrane proteins are generated in the lumen of the ER
    • Cytosolic proteins are made in the cytosol by free ribosomes
    • Post translational modifications
    • N-glycosylation
    • N-glycosylation is the addition of oligosaccharides to terminal nitrogen of an asparagine amino acid. This process begins in the rough ER
    • Reducing environment of the RER allows for disulfide bonds to be made.
    • Chaperone proteins
    • Needed to complete protein folding so protein can function properly. They bind to proteins to allow for 2, 3, 4 structures
    • Calnexin
    • Calreticulin
    • Lipid Synthesis
    • Cytosolic side of RER or ER because that’s where the enzymes are
    • Slide 4
    • Fatty acyl Coenzyme A and glycerol-3-phosphate
    • As lipids are generated, phosphotitic acid is generated as fatty acids are taken from fatty acyl CoA and put them on G3P
    • Acyl transferase is involved in transferring fatty acids to GP to generate Phosphotitic acid which is then embedded into the membrane.
    • Hydrophobic fatty acids help embed phosphotitic acid into membrane
    • Other enzymes generate the subsequent phospholipids in the membrane
    • Phosphotase that takes off Pi form phosphositic acid that makes diacyl glycerol that is an important signaling molecule
    • Diacyl glycerol has signal regions in hydrocarbon regions but when flipped, exposed to luminal side.
    • Phosphotidle chloline
    • CDP
    • Cytodine di/bis phosphate that is joined to diacyl glycerol by this enzyme, cholin phospho transferase, transferase takes component of molecule and transfer to another
    • Phosphotidal choline embedded into membrane after being converted form diacyl glycerol
    • ____________________________________________
    • As phospholipids are generated, phosphoatic acid (listen to lecture 11:50)
    • Fatty acyl coenzyme A
    • Acyl transferase >>> G3P
    • Glycerol-3-phosphate
    • CDP – cytodine-di/bis-phosphate
    • Joined to diacyl glycerol by choline-phopho-transferase
    • CPH – converts diacyl glycerol to
    • Phosphoticid acid – ph
    • _____________________________________________________________________
    • Slide 5
    • Family of Flippases
    • Proteins called scramblases
    • Phospholipid Transporters
    • can flip phospholipids in only one direction but at other times, flip back and forth
    • Golgi Stack
    • Post translational modifications of proteins
    • Three regions
    • Cis region
    • N-glycosylation
    • Medial region
    • Phosphorylation
    • O-glycosylation
    • Oligosaccharides placed onto the O of OH on a serine/threonine
    • Trans region
    • Made of flattened cisternae
    • Sugars on the proteins also protect the protein from degredation
    • N and O glycosylation is done on phospholipids of lysosomes because they are exposed to harsh environments/ enzymes in the lysosomes
    • Receptors that recognize specific signal sequences in transport vesicles.
    • As vesicles bud, they are trafficked to specific organelle, plasma membrane, or secreted.
    • Two types of movement from the golgi
    • Constitutive
    • Movement of lysosomal enzymes that are generated in ER then trafficked to golgi, then trafficked to lysosomes
    • Regulated
    • Intermittently
    • Specific signal stimulates synthesis
    • A regulated pathway
    • Transition vesicles take proteins that will undergo post-translational modification as well as then be tranfficked to particular regions after the golgi, then they move them to the golgi
    • From golgi to membrane, or organelles etc, are called secretory vesicles.
    • Lysosomes
    • Acid environment (5.5ish)
    • Made of more than 40 different enzymes that can break apart molecules that are no longer toxic to cell or can be reused by cells.
    • Nucleases
    • Nucleic acids to nucleotides
    • Proteases
    • Protieins to amino acids
    • Glycosidases
    • Disaccharides/polysaccharides to monosaccharides
    • Lipases
    • Phosphatases
    • Phosphates from protein groups
    • Sulfases
    • Break down sulfate groups
    • Phospholipases
    • Breaks down phospholpids
    • ATP hydrolysis and continual transport, active, of protons into lysosome.
    • Acidic environment is necessary for these enzymes
    • Requires energy to bring in H+
    • Contain Metabolic transporters
    • Pumps out individal materials, such as amino acids etc, into cytosol to be used by the cell
    • Need facilitated diffusion for this, a protein
    • Slide 11
    • Early endosomes are a sorting place for many components, they can act as a retrafficking/reuse receptor site that go to the membrane and bring ligands back to the cell, or continue to late endosomes, ~6.5ph as compared to cytosol 7ish
    • In late endosome, become more acidic 6ish, hydrolases are found in late endosomes, but less acidic that lysosomes
    • For complete degredation, late endosomes fuse with lysosomes and the lysosomes are sites with highly acidic environenment.
    • Vesicles undergo endocytosis
    • Endocytic vesicles are transported to early endosomes, a sorting place for many componenets
    • Can go to a late endosome which has a more acidic environment ~6
    • Mannose-6-phosphate receptors
    • Manose receptrs outside are recognized by this and when they are bound they bud to endosomes and released due to acidic environment and then are broken down. Carried to late endosome or lysosomes
    • Slide 12
    • Autophagy
    • Cell surrounds constituents within cytoplasm through outpocketing of endoplasmic reticulum around the outside of dead old or dying organelles and creates a vacuole called an autophagosome, and it fuses with lysosome to make an autophagolysosome and enzyme of that can degrade organelle.
    • Phagocytosis
    • Means for cell to extend pseudopodia out and around foreign particles, bacteria, dying cells, and engulfed and fused. Formed into a vacuole that is called a phagosomes.
    • They are trafficked and fused to lysosomes to make a phago-lysosome.
    • Now the organelle can digest foreign material
    • Isolated organelles self-repliacate
    • Peroxisomes have characteristics of both categories of organelles
    • Can bud off of endomembrane system
    • Undergo fission event that allows the cell to make more of them, making them isolated organelles
    • Peroxisomes are:
    • Like lysosomes
    • Have an oxidative rather than acidic environment
    • Oxidizes particular constituents in cell that are toxic or to byproductst that are not toxic to be used
    • Catalase alters H2O2 so the cell can handle it.
    • Breaks down to H20 and O2
    • Take off H from organic compounds and generate H20 and an organic compound not damaging