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CELL STRUCTURE Module 1

An introduction to pharmacy

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CELL STRUCTURE Module 1

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  1. CELL STRUCTURE Dr. Kenneth Orimma B.Sc., M.Sc., M.B.B.S, D.I.R,D.M(Doctor of Medicine)Psychiatry

  2. CELL STRUCTURE Cytoplasm o Everything inside a cell bar the membrane and the nucleus o Includes all organelles + cytosol Cytosol o The fluid found within the membrane but outside the organelles § Largely water with dissolved protein, salts, sugars & other solutes Inclusions o Chemical substances § Glycosomes § Glycogen granules § Pigment

  3. CELL STRUCTURE Cytoplasmic Organelles: Membranous Organelles Nucleus • Nuclear envelope, Nucleoli, Chromatin • Contains the genetic library for nearly all cellular proteins • Is the place where mitosis begins Mitochondria • Cell power station • Double Membrane • Synthesize ATP for energy

  4. CELL STRUCTURE Endoplasmic reticulum (Rough/Smooth) Rough: o Covered with ribosomes (hence rough) o Synthesis of all proteins secreted from cell + membrane proteins + protein hormones o Proteins synthesized by ribosomes are then packaged in the Rough ER for export from the cell o Assist in making cellular membranes Smooth: o Not covered with ribosomes (hence smooth) o Doesn’t synthesize proteins o Metabolizes lipids o Synthesizes steroid-based hormones (testosterone/estrogen) o Detox of drugs/xenobiotic chemicals o Storage site of calcium ions in skeletal/cardiac muscle

  5. CELL STRUCTURE Golgi apparatus • The cellular courier • Modifies, Concentrates and packages proteins and membrane synthesized in the Rough ER for intracellular transport or excretion • Packaged proteins/membranes are released from the ‘shipping face’ in a transport vesicle for either excretion or cellular functions

  6. CELL STRUCTURE Lysosomes: • Membranous sacs created by the Golgi • Contain concentrated enzymes • Inside is acidic for max enzyme function • Destroy ‘old’ cellular material • Destroy bacteria/viruses engulfed by white blood cell Peroxisomes • Membranous sacs • Contain enzymes • Detoxify harmful xenobiotic substances (alcohol) • Neutralizes highly reactive free radicals (by-products of biochemical processes)

  7. CELLULAR STRUCTURE Non-Membranous Organelles Cytoskeleton • Elaborate network of large filamentous rod-like proteins • Provide structural support • Provide the central mechanism for movement • Ensures the distribution of organelles throughout cell

  8. CELLULAR STRUCTURE Ribosomes • Composed of protein & ribosomal RNA (rRNA) • Are the site of protein synthesis • Found either on the Endoplasmic Reticulum or free in the cytosol • ERs with ribosomes are called ‘Rough’ ER

  9. TRANSPORT CROSS CELL MEMBRANE Imbedded Proteins in cell membrane: Peripheral: § Associated with the polar head groups § Easily removed from the membrane by Δ pH or Δ [salt] Integral: • § Embedded in the membrane • § Span the width of the membrane • § Membrane must be destroyed to remove it • • Done by adding detergent (small amphipathic molecules)

  10. TRANSPORT CROSS CELL MEMBRANE How Substances Cross Cell Membranes: • Membrane controls the flow of materials in/out of the cell • Either passive or active processes:

  11. TRANSPORT CROSS CELL MEMBRANE Passive Transport: Diffusion o Simple Diffusion – movement of small, uncharged, non-polar and lipid-soluble substances directly through the lipid bilayer (O2, CO2, N, Ethanol, Glycerol, Steroids, fat soluble vitamins) o Facilitated Diffusion – where specific molecules diffuse across membranes, through specific transport proteins (Carrier/channel) o Factors Affecting Rate of Diffusion: § Concentration gradient § Molecular size § Temperature (faster @ higher temps) § Electric or Pressure gradient

  12. TRANSPORT CROSS CELL MEMBRANE Passive Transport Proteins (Aka: Facilitated Diffusion): • facilitate the diffusion of specific chemicals • (glucose/amino acids/nucleotides/ions) through the membrane that would otherwise not pass through the bi-lipid layer

  13. TRANSPORT CROSS CELL MEMBRANE #1 Passive Carrier Proteins: • Discriminates between solutes based on the shape of the protein’s binding site • - then transfers single molecules across the membrane by changing its conformation (similar to a turnstile) • Has a high affinity for its substrate • - are therefore very effective at low substrate concentration • Transfer rate is inhibited by temperature • Uniporters: single solute → down the concentration gradient §#2 Passive Channel Proteins: Discriminates between solutes mainly on size and electric charge (usually transports ions • Act like a tube that is either opened/closed • Has no affinity for its substrate (substrate flow is determined by the concentration gradient of that substrate) • Once opened, ion flow is very rapid • Not affected by temperature

  14. TRANSPORT CROSS CELL MEMBRANE Osmosis – The passive transport of water across a selectively permeable membrane o Survival of the cell is dependent on osmoregulation o Water will flow from the hypotonic solution to the hypertonic solution through the lipid bilayer to form an isotonic solution

  15. TRANSPORT CROSS CELL MEMBRANE Active Processes: • Transports substances against their concentration gradient • Transports substances that would otherwise be too large for channel proteins Active Transport (via carrier proteins): o (using energy –ATP- to move molecules across a membrane) o Similar to passive facilitated diffusion in that it requires carrier proteins o Active transporters (solute pumps) differ from facilitated diffusion in that they move solutes (mostly ions – Na+, K+, and Ca2+) uphill against their concentration gradients o In so doing, ATP is expended

  16. TRANSPORT CROSS CELL MEMBRANE 2Classes:Primary&SecondaryActiveTransport • Distinguishedaccordingtotheirsourceofenergy • PrimaryActiveTransporters: • EnergycomesdirectlyfromthehydrolysisofATP • Solutebindstotheactivesite–thentheproteinisphosphorylated,causingitto changeitsshapeandreleasethesoluteontotheothersideofthemembrane • Eg:TheSodiumPotassiumPump(TheNa+/K+-ATPaseEnzyme) • AnAntiporter:2solutesmove in oppositedirections bothagainstconcentration gradients • CytoplasmicNa+bindstotheprotein,stimulatingphosphorylationbyATP • Phosphorylationcausesproteinshapetochange • ChangeinshapereleasesNa+totheoutside • K+thenbindstotheprotein,triggeringthereleaseofthephosphategroup • Lossofphosphaterestoresproteintooriginalshape • K+ionsarethenreleasedintothecell • Cyclethenrepeats

  17. TRANSPORT CROSS CELL MEMBRANE

  18. TRANSPORT CROSS CELL MEMBRANE • SecondaryActiveTransporters: • Symporters:Usingthepotentialenergyoftheconcentrationgradientcreatedbyaprimarytransporter,thehighconcentrationsoluteflowsdownhill,draggingwithit anotherchemical • Eg:Na+-GlucoseSymporter

  19. TRANSPORT CROSS CELL MEMBRANE ActiveTransportViaVesicles: • Transportoflargeparticles,macromoleculesandfluidsthroughcellmembranes • Exocytosis:Vesiculartransportofsubstancesoutofacell(secretion) • Endocytosis:Vesiculartransportofsubstancesintoacell • Phagocytosis:alargeexternalparticleisengulfedandenclosedinavesicle(eg:inwhite bloodcells) • Pinocytosis:externalfluiddroplet(containingsmallsolutes)isengulfedandenclosedina vesicle(absorptivecells–eg:kidney&intestine) • ReceptorMediated:selectiveendocytosis–substancebindstomembranereceptors&then enclosedinavesicle

  20. TRANSPORT CROSS CELL MEMBRANE

  21. TRANSPORT CROSS CELL MEMBRANE:ThreeFormsof endocytosis

  22. CELL MEMBRANE & TRANSPORT: ThreeFormsofEndocytosis • Endocytosisisaformofactivetransportinwhichacellenvelopesextracellularmaterials usingitscellmembrane. (a)Inphagocytosis,whichisrelativelynonselective,thecelltakesinalargeparticle. (b)In pinocytosis,thecelltakesinsmallparticlesinfluid. (c)Incontrast,receptor-mediatedendocytosisisquiteselective. • Whenexternalreceptorsbindaspecificligand,thecellrespondsbyendocytosingtheligand.

  23. CELLULARMETABOLISM

  24. CELLULARMETABOLISM WhatisMetabolism? • Metabolismisacell’scapacitytoacquireenergy,build,breakapart&releasesubstances • Includingextractingchemicalenergyfromfoodthroughmetabolicprocesses • Metabolicreactionsleadtosomeenergylosstotheenvironment(generallyheat) • Metabolicreactionscanreleaseorrequireenergy • Why cell metabolism?Cellsengageinmetabolismtosurvive,repair,replicateandcarryouttheirfunctions • Didyouknow:Alltheenergyinallthefoodyoueatcanbetracedbacktosunlight • Thechemicalenergystoredinfoodisintheformofsugarsandotherorganicmolecules • Note:Cyanide&CarbonMonoxidekillyoubydisruptingcellularrespiration

  25. CELLULARMETABOLISM AutotrophsandHeterotrophs: • Autotrophicorganisms("self-feeders"or“producers”)canconvertinorganicsubstrates(CO2andH2O)into complexorganicmoleculessuchassugars(tomakeATP)neededforthecatabolicreactionsinthecell • Eg:Plantsandalgaethatphotosynthesize • Heterotrophicorganisms(“Consumers”)canonlyextractenergybybreakingdowncomplexmolecules (sugars/fats/etc)throughrespiration • Eg:Mostanimalsincludinghumans

  26. CELLULARMETABOLISM ATP(AdenosineTriphosphate): • ATPisthemainenergycarrierinthecell(OthersincludeNAD,NADH) • ATPisgeneratedinthecellbyoxidationofnutrients(Includingcarbohydrates,aminoacids,lipids) • ATPisconsumedbyanyactive/constructiveprocessundertakenbythecell

  27. CELLULARMETABOLISM

  28. CELLULARMETABOLISM

  29. CELLULARMETABOLISM • ATPformswhenaphosphateisdonatedtoADP(AdenosineDiphosphate) • ATPform-→ADP+P(inorganic)+Energy • ADPform-→AMP+P(inorganic)+ Energy

  30. CELLULARMETABOLISM AerobicMetabolism(Aka:Respiration): • Oxidationofnutrientsgenerallyrequiresoxygen • Hencewhythemajorityofcellsrequireoxygenforthemajorityofthetimeinordertosurvive • Aerobicmetabolismisthemostefficientwaytoreleaseenergyfromnutrients • Canonlyoccurinthepresenceofoxygen • Requiresthecelltobeabletoexchangegaseswithitssurroundings

  31. CELLULARMETABOLISM AnaerobicMetabolism: • Certaintissuesarecapableofsurvivingviaanaerobicmetabolismincertaincircumstances • Extractingenergyfromfoodwithoutoxygenisnotasefficient(lowerATPyield)andproducesadditional metaboliteswhichneedtobeprocessedlaterorexcreted(Eg:Lacticacid) • Occurswhenthedemandforoxygenoutstripsthebody’sabilitytodeliverit

  32. CELLULARMETABOLISM MetabolicPathways • Burningmultiplefuels(nutrients)requiresmultiplemetabolicpathways: • Carbohydrates: • Glycolysispathway • Pentosephosphatepathway • TheCitricAcidcycle(TCA),aka:‘TheKrebsCycle’ • TheElectronTransportChain(‘Oxidativephosphorylation’) • (Glycogenesis/Glycogenolysis)–Glucosestorage&retrieval • (Gluconeogenesis)–Glucosesynthesisfromothersubstrates • AminoAcids: • AminoAcidMetabolism • TheUreaCycle • Lipids: • FattyAcidOxidation • Ketogenesis/Ketolysis • (FattyAcidSynthesis)

  33. CELLULARMETABOLISM • EachMetabolicpathwayisanorderlyseriesofreactionsdrivenbyenzymes • Enzymesarecatalysts–theylowertheactivationenergyofareaction+bindsubstrates • Differenttissue-typeshavevaryingmetaboliccapabilities: • Eg:Musclespreferentiallyburnglucose • Eg:Livercellscanhandle/transformmultiplenutrients • Eg:Heartmusclecanburnglucoseorketonebodies • Eg:Braincanburnglucoseorketonebodies

  34. HormonalRegulationofMetabolism:

  35. HormonalRegulationofMetabolism:

  36. CARBOHYDRATEMETABOLISM OverviewofCarbohydrateMetabolism: • Energyisstoredinthechemicalbondsofcarbohydrates • EnergyisreleasedasthesechemicalbondsarebrokendownandoxidizedtoCO2andH2O • Thisenergyistransferredtoactivatedcarriermoleculeswhichserveasportableenergysources • Eg:ATP • Eg:NADP/NADPH/NADH2/NADH+ • RegulatedbyInsulin,Glucagon&‘Counter-RegulatoryHormones’: • Insulin:Promotesdecreaseinblood[glucose]byincreasinguptake(glycolysisorglycogenesis) • Glucagon:Promotesincreaseinblood[glucose]byincreasingoutput(gluconeogenesisand glycogenolysis) • *Adrenaline/Cortisol:Promotesincreaseinbloodglucose

  37. CARBOHYDRATEMETABOLISM • GLYCOLYSIS: • Whatisgycolysis? • Theenergy-producingbreakdownofGlucoseintoPyruvate • Thebeginningpointofcellularcarbohydratemetabolism • Note:Othernon-glucosesugarsmustfirstbeconvertedtooneoftheglycolyticintermediates • Wheredoesgycolysisoccur? • IntheCytoplasmofallcells • Therefore,firstrequirestheuptakeofextracellularglucoseINTOthecellviatheGLUTtransporter • UptakeofextracellularglucoseisregulatedbyInsulin • Somecells(RedBloodCells)relyexclusivelyonglycolysisforenergy(nomitochondria)

  38. CARBOHYDRATEMETABOLISM Glycolysis continued Summary:Glycolysisconverts1xGlucosemoleculeinto… • 2xPyruvates (Whichthenpassintothemitochondria→TCA/KrebsCycle) • 4xATP–Netgain=2ATP’s (2spent,4produced) • 2xNADH–Netgain=2NADH’s (0spent,2produced)

  39. CARBOHYDRATEMETABOLISM THECITRICACIDCYCLE(TCA)/‘KREBSCYCLE’: • WhatisKreb’s cycle? • TheintermediatestepbetweenGlycolysis&OxidativePhosphorylation(ElectronTransportChain) • GlycolysissuppliestheTCAcyclewithPyruvate • TCACyclesuppliestheElectronTransportChainwithNADH,FADH, • WheredoesKreb’s cycle occur? • OccursintheMitochondriaofAllCells(ExceptRBCs) • RequiressufficientglucoseconcentrationinthecytoplasmtomaintainconstantsupplyofPyruvate • Note:PyruvateisconvertedtoAcetyl-CoAuponentryintotheMitochondria: • Produces1xNADH(worthapproximately 3ATP) • Consumes1xCoenzymeA • Liberates1xCO2molecule

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