2 ObjectivesList the principle functions and describe the structure of the nucleus, mitochondrion, endoplasmic reticulum, Golgi, lysosomes and peroxisomes in higher eukaryotesDescribe the modification and transport of proteins from the ER through the GolgiDescribe the intracellular transport of proteins from the trans Golgi network to lysosomesDescribe the structure of the mitochondrion and the process of ATP synthesisDescribe the contribution of organellar dysfunction to the development of disease
7 Nucleus The largest organelle in eukaryotes Surrounded by 2 phospholipid bilayersInner nuclear membrane defines the nucleus itselfOuter nuclear membrane is continuous with the rough ERSpace between the inner and outer membranes is continuous with the lumen of the rough ER
8 NucleusThe two nuclear membranes fuse at the nuclear pores which regulate movement of molecules between nucleus and cytosolContains the DNA of eukaryotic cellsDNA is packaged into chromosomes in metabolically active nuclei (growing or differentiating cells)The cell’s rRNA is synthesized in the nucleolus (a suborganelle)
14 Ran GTPases drive directional transport through nuclear pore complexes Ran is a molecular switchTwo conformationsdependent on what is bound to itRan-GEF is in the nucleusGDP to GTP“Cocks the hammer”Creates a gradientRan-GAP is in the cytosolGTP to GDPUses energy to import“pulls the trigger”
16 Endoplasmic reticulum Second largest cellular organelleHas many functions, but primarily important in the synthesis of membrane lipids and proteinsTwo types: rough and smooth
17 Smooth Endoplasmic reticulum Functions in synthesis of fatty acids and phospholipidsAbundant in hepatocytesenzymes in SER detoxify hydrophobic chemicals such as pesticides and carcinogens to water soluble compounds that can be excretedHigh doses of these compounds result in LOTS of SER proliferation
18 Rough Endoplasmic reticulum Ribosomes bound to the surface make it “rough”Responsible for synthesis membrane and organellar proteins and virtually all proteins that are to be secreted from the cellRibosomes that make these proteins are bound to the ER by the newly growing peptide chainThe newly made protein passes through the RER with the help of specific proteinsThese new proteins accumulate in the lumen of the RER and await transportVery abundant in cells that produce secreted proteins: plasma cells (antibodies), pancreatic acinar cells (digestive enzymes)
24 Golgi Responsible for protein modification and transport Divided into the cis-, medial and trans- GolgiTransfer vesicles from the ER fuse with the cis- region and deposit proteinsAfter movement through the Golgi, they bud off through the trans- side
27 Transport of proteins from trans-Golgi to lysosomes Lysosomal hydrolases carry a makerMannose 6-phosphate (M6P)M6P groups are recognized by M6P receptor proteins in trans-GolgiBind to lumenal side by way of adaptinsAdaptins interact with clathrin molecules on the cytosolic sideShuttled to late endosome where pH change releases hydrolase
29 Peroxisomes Contain oxidases – enzymes that generate hydrogen peroxide Large amounts of catalase – degrades hydrogen peroxide to water and oxygenOxidation is NOT linked to ATP generationProduce acetyl groups that are used in the production of cholesterol and biosynthetic molecules in animal cellsAlso degrade toxins produced by liver, kidney cells, etc.
31 Peroxisome-assembly related diseases X-linked adrenoleukodystrophy (ADL)Defective oxidation of very long chain fatty acidsADL gene encodes the peroxisomal membrane protein that transports an oxidative enzyme into the peroxisomesEffects are evident in mid-childhood: severe neurological disorders followed by death within a few years
32 Peroxisome-assembly and function related diseases Pseudo-Zellweger syndromeBeta-oxidation disorder (fatty acid metabolism)Other peroxisomal functions remain intactSymptoms are present at birthMajor body systems are affected: vision, kidneys, cartilage, heart, muscle and liver
37 Lysosomal Storage Diseases Caused by genetic defectsResult in accumulation of undigested substrates in lysosomesUsually act on nervous systemHurler’s syndromeCaused by mutation on gene that codes for enzyme that breaks down glycosaminoglycanResults in deformation and retardationI-cell diseaseSevere form of Hurler’s syndromeDetected by inclusion bodies in tissue cellsCell hydrolases are misdirected and secreted
38 Tay Sachs Disease1 in 27 Jews in the U.S. are carriers of the defective Hex-A geneFrequency in the general population is 1 in 250Over 50 DNA mutations have been identified in the Hex-A geneDNA testing is usually done in conjunction with biochemical testing for Hex-A levels in the blood
39 Tay Sachs DiseaseIndividuals are lacking the ability to break down gangliosides (glycolipids)Symptoms usually appear before age 1Children become blind and demented by age 2Usually fatal by age 3Nerve cells are greatly enlarged with swollen, lipid-filled lysosomes
42 Mitochondria Up to 25% of cytoplasm volume Main site of ATP production Inner and outer membraneOuter membrane allows molecules up to 10,000 mw to pass through, much like gram negative bacteriaInner membrane is composed of cristae that function to increase oxidative surface area
43 Mitochondria Fuels for ATP synthesis are fatty acids and glucose Degradation of 1 glucose to CO2 and H2O can yield up to 36 ATP moleculesInitial stage producing 2 ATPs’ occurs in the cytosolTerminal stages producing up to 34 ATP’s are carried out by mitochondrial enzymes in the matrix and cristae
48 Summary PointsAll eukaryotic cells contain a membrane bound nucleus and organelles in their cytosolLysosomes, which are found only in animal cells, have an acidic interior and contain various hydrolases used to break down cellular componentsPeroxisomes are small organelles containing enzymes that oxidize various organic compounds, generating hydrogen peroxide
49 Summary PointsMitochondria are bound by two membranes, the inner one extensively folded. Enzymes in the inner mitochondrial membrane and central matrix carry out the terminal stages of sugar and lipid oxidation coupled to ATP synthesisSecretory and membrane proteins are synthesized on the RER (a network of membrane vesicles studded with ribosomes). These proteins move to the Golgi complex where they are stored and processed
50 Summary PointsThe nucleus is surrounded by an inner and an outer membrane. Movement of molecules into and out of the nucleus occurs through the nuclear pores. The outer nuclear membrane is continuous with the RER.The cytosol is the portion of the cell’s interior that remains after you take away all of the organelles. There are a lot of proteins in it – lots of soluble enzymes, actin microfilaments, microtubules and intermediate filaments. These help to give the cell some sort of structure.
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