Pharm 120 Module 1.1 Cytology

• plasma membrane

  structure: lipid bilayer

  • head: glycerol+ phosphate = hydrophilic
  • tails: fatty acids = lipophilic
• plasma membrane

  • the double bonds of cholesterol allow fluidity because of their arrangement
  • allows interactions, movement of components, processes and self sealing in plasma membrane
• plasma membrane (membrane proteins)

  • integral protein (Embedded) - drug target
  • peripheral protein
• drug targets

  • integral proteins

  1. g-protein coupled receptors, ion channels, transporters, tyrosinase kinase, enzymes, and other glycoproteins
  2. disrupting the membrane itself
  3. a. prokaryotes: glycopeptides, daptomycin, bacitracin
  4. b. eukaryotes: antifungals
• plasma membrane (membrane permeability)

  • selective permeable - allows non polar and small, polar molecules
  • large polar molecules, ions =no
• plasma membrane (gradient)

  • concentration gradient - concentration of chemicals
  • electrical gradient - electrical charges
  • combined - electrochemical gradient
• membrane transport mechanisms

  • passive transport gradients - along gradient

  1. simple diffusion
  2. facilitated diffusion
  3. osmosis
  4. filtration

  • active transport process - against gradient

  1. active transport - primary, secondary
  2. vesicle transport - endocytosis, exocytosis
• simple diffusion

  • passes freely through membrane
  • transport from higher to lower concentration
  • non polar, hydrophobic molecules like gases, fatty acids, adek, small and uncharged molecules like water, urea
• simple diffusion 


  function

  1. gas exchange
  2. nutrient absorption, waste secretion
• brownian movement

  • random movement of small particles
  • affects stability of proteins in solution - e.g. insulin
  • airway deposition of nasal sprays and inhalations
  • suspension
• facilitated diffusion

  • assisted by integral membrane protein
  • channel mediated

  1. via ion channels

  > ligand-gated to open it and close it - e.g. GABA

  > voltage-gated triggered by changes of voltage inside/outside the cell

  > carrier mediated - via certain kind of transporters, finite number of carriers, saturatable (there could be competition with the molecules with same structure) e.g. glucose, fructose, galactose, vitamins
• osmosis

  • movement of water through semipermeable membrane

  1. hydrostatic pressure - applied by fluid (gravity, density, etc)
  2. osmotic pressure - pressure to stop water flow based on solute concentration

  note: there must be a presence of a semi permeable membrane. otherwise, this will just be a simple diffusion
• water can also move via aquaporins (Water channels)

  • aquaporin help regulate cellular water content and with the production of body fluids like tears, saliva, urine, etc
• isotonicity

  • remember that the isotonic concentration of NaCL is 0.9% - cell is in spherical round, biocave
  • hypotonic - cell will swell
  • hypertonic - cell will shrink
• drug targets using osmosis

  • osmotic diuretics - filtered to urine freely, water is towards the urine, increases osmotic water to keep water in urine
• filtration

  • movement of water and solute in the membrane via hydrostatic pressure
  • e.g. dialysis
• active transport processes

  • movement against concentration gradient
  • needs energy in the form of ATP
• primary active transport - sodium-potassium atpase

  • allows movement of potassium inside the cell, at the same time the movement of sodium outside the cell.
  • 2 potassium, 3 sodium
  • hydrolyzes ATP to allow the conformational change of the pump
• secondary active transport

  • uses concentration gradient made from the primary
  • e.g. using the established concentration of PISO PUMP
• other transport

  • na-ca: sodium in, calcium out, antiporter
  • na-H: for regulation of pH, symporter
  • na-glucose: regulation of urine in kidney, symporter
  • na-AA: aa absorption, both anti and symp
• Endocytosis 


  vesicle transport into the cell via vesicle formed from the membrane

  types:

  • receptor mediated (Common)
  • phagocytosis
  • bulk phase (pinocytosis)
• receptor-mediated

  • a ligand will bind in the receptor found in the plasma membrane (outside)
  • an adaptor protein will bind in the cytosolic half of the receptor
  • membrane curvature will happen
  • clathrin will come and form a coat, becomes vesicles and will be detached from the membrane, making the vesicle be transported inside the membrane
  • vesicle will be met by endosome which will detach ligand from the receptor
  • both receptor and ligand may be recycled or degraded
• down-regulation

  • if your body figures out that you are giving so much agonist, it should slow down by decreasing membrane receptor via receptor mediated endocytosis
  • less receptors means high tolerance, thus concentrated drugs are needed to interact
  • can be done to reduce side effects
• drug about receptor-mediated endocytosis

  • statins & ezetimibe (cholesterol lowering medicines) - causes increased LDL receptor -- more cholesterol undergoes endocytosis
  • some drugs prevents endocytosis of viruses by binding to the proteins involved.
• phagocytosis

  • cell eating
  • via phagocytes

  1. macrophage - WBC that surrounds the bacteria and destroy it, also eliminates dead cells and boosts activity of the other immune system cells
  2. neutrophils - WBC that boosts immune system, defends body against illness, earliest to react when a phagocyte enter the body, consumes and releases enzyme that kills the germs
• pinocytosis

  • cell drinking via pseudopods (false-feet) where it is utilized to move
  • cell membrane folds and forms tiny pockets to accumulate the extracellular fluid and dissolved materials
• exocytosis

  secretes vesicle forms inside the cell

  • secretes contents of the cell
  • fuses with cell membrane
  • releases content (neurons: neurotransmitters, secretory cells: hormones, mucus, enzymes etc)
• exocytosis 


  drug targets

  botox

  • stops protein involved in exocytosis: no acetylcholine will be released: no muscle contractions
  • not just for cosmetics but also for cervical dystonia
• transcytosis

  • mucosal transport
  • enables membrane-impermeable macromolecules to enter cell and reach nearby tissue
  • encourages redistribution of lipids and proteins
  • combination of both endo and exo
• cytoplasm

  • everything in between the nucleus and the plasma membrane

  1. cytosol and cytoskeleton
  2. organelles
• cytosol

  • not equal to cytoplasm
  • liquid portion of cytoplasm, ICF (mostly water - 75-90%) and dissolved components
  • ions, glucose, amino acids, proteins, waste products
  • where most essential cellular chemical reactions occur
  • contains cytoskeleton
• cytoskeleton

  • structural in nature
  • various form have various function
  • network of protein filaments, serves as structures

  1. microfilaments
  2. intermediate filaments
  3. microtubules
• microfilaments

  • thinnest and smallest
  • components: actin and myosin
  • prevalent at cell edge

  functions:

  • movement - cell division, muscle contraction, cell locomotion
  • mechanical support - anchor cytoskeleton to membrane integral proteins; support microvilli (non motile fingerlike projection of plasma membrane, increases surface area)
• intermediate filaments

  • thickest in between microtubules and microfilaments

  functions:

  • structural support
  • regulation of several fundamental cell processes: growth, apoptosis, proliferation,
• microtubules

  • largest
  • long, unbranched, hollow
  • composed of tubulin
  • assembled in centrosome -- grow outwards

  function:

  • cell shape, movement of organelles, found in cells

  drug target

  • antineoplastic agents like colchicine
  • involved in pathologic mechanism in heart disease (stroke and heart attack)
• centrosome 


  microtubule organizing center

  • 2 centrioles + pericentriolar matrix
  • centrioles (9 microtubules) + pericentriolar matrix (ring shaped)
• cilia

  • hairlike projections
  • sweeps mucus
  • inability of cilia to sweep will cause for mucus to build up \
• flagella

  • like cilia, but longer
  • for movement like in sperm
• ribosome 


  rRNA + protein

  function: protein synthesis
• central dogma

  • replication - DNA--> new DNA
  • transcription - DNA-->RNA
  • translation = RNA --> proteins
  • those attached to er, nuclear membrane (bound for plasma membrane, organelles and transport
  • free ribosomes - cytosol proteins