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Keep an in-class experiential diary today*

Keep an in-class experiential diary today*. If you have any food issues (allergies, reactions) don’t do any of this, please. I know of no significant risk, but I get paid less whenever someone dies before the drop date. Use a friend’s observations

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Keep an in-class experiential diary today*

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  1. Keep an in-class experiential diary today* • If you have any food issues (allergies, reactions) don’t do any of this, please. I know of no significant risk, but I get paid less whenever someone dies before the drop date. • Use a friend’s observations • Try some diet DP. Record observations; focus on sweetness • Get a ‘lemon or lime kit’. When your mouth is totallyfree of other tastes, you may ‘suck a citrus’. Leave one section for later!! • Record observations; await further instruction *You’ll need it for the homework

  2. Oh, the weather outside • There’s more to protein folding, structure, activity than just water & amino acid sequence. • And it matters.

  3. Atom parts • What’s this? • What happens when its electron gets ‘shared’ away? Freeman, Biological Science, Fig. 2-1

  4. What happens when you... • go outside and it’s raining? • visit friends with a pet and not much cleaning up? An experimental demonstration of consequence of pH Step I: squeeze a lemon quarter into your mouth. Mmmmm Mmmmm good!

  5. A word on nomenclature • Hydrogen concentrations can vary a lot--like, 1,000,000,000,000-fold • Inconvenient! We speak of ‘puissance d’hydrogene’ (‘power of hydrogen’, according to your text) or pH • look to pure water (hydrogen ion concentration 10-7 molar), extract the exponent (10-7), positivize it & declare ‘pH 7’ • Thus: pH = negative (logarithm of concentration H+) • i.e. pH = -log[H+]

  6. Relative 1/10,000 1/1,000 Rarer free H+ 1/100 1/10 10x 100x 1,000x More free H+ 10,000x 100,000x 1,000,000x ! Watching H+(from tiny to tons) Clarity: An acid gives up its pH to become negatively charged, but the solution it’s in gains an H+ Fig 2.16

  7. Histidine sidechain 50% positive Glutamic acid sidechain 50% neutral Lysine sidechain 50% neutral Amino acid balances of power Alert: This is a poorly thought out color scheme. Protons are morecommon at the bottom (alas, shown as red) Fig 2.16

  8. Picking on Histidine • Fill in: while carbon makes __A__ [#] bonds b/c it has __B__ [#] outer shell electrons, nitrogen makes __C__ [#], oxygen _D_ [#] • What are the 2 non-bonding electrons of nitrogen doing? the 2 PAIR of non-bonding electrons in oxygen? • How do those pairs ‘feel’? http://forums.studentdoctor.net/showthread.php?t=770938

  9. at pH 7, proton mostly loaded. positive charge at pH 6, 1/2 neutral, 1/2 positive: in the balance! at pH 7, proton mostly gone. negative charge Sidechain ‘behavior’ pKa: the concentration of protons (pH) at which 50% of the group in question has an H+ on board http://upload.wikimedia.org/wikipedia/commons/0/0f/Amino_acids.png Note: the image is linked from the homepage ‘sources’ menu as ‘aa sidechains’

  10. But who cares? Does pH matter? • Argument I: Ever heard of ‘the flu’ ? • Argument II: What happened to your lemon?

  11. First, though... ONCE the lemon sourness gone, suck on your pill. Do not chew; goal is to coat tongue thoroughly

  12. Background In the United States, seasonal influenza epidemics typically claim the lives of about 30,000 people each year and cause hospitalization of more than 100,000 (Reid & Tautenberger, 2003). Every two or three years, more virulent strains circulate, increasing death tolls by approximately 10,000 to 15,000 individuals*. These seasonal epidemics are the result of antigenic drift, a phenomenon caused by mutations in two key viral genes due to an error-prone RNA polymerase.*** Clancy, S. (2008) Genetics of the influenza virus. Nature Education 1(1) *The one in 1918 killed 50-100 million worldwide ***Being small, it can get away with a ‘lesser’ nucleic acid (RNA) as its genome note that inevitable errors actually provide periodic advantage

  13. Outside cell • Virus stick to cell surface protein • Cell engulfs; creating vesicle (‘endosome’; first step in eating) • Cell seeks to destroy by pumping in protons (cell thinks “I will destroy & eat!”) • Virus fuses its membrane with vesicle, releasing genome (RNA) into cytoplasm!!! • You sneeze for a week… or (occasionally) die http://cbm.msoe.edu/

  14. A molecular saboteur http://www.rpc.msoe.edu/cbm/resources/HAAnimation.swf

  15. pH 7 pH 5 http://www.rpc.msoe.edu/cbm/ currentprograms/curIHP.php Harpoon! http://www.rcsb.org/pdb/education_discussion/molecule_of_the_month/download/Hemagglutinin.pdf

  16. Where, what, when http://www.mcb.uct.ac.za//cann/335/335Rep2.jpg

  17. So what? • These are ways to influence a protein from without • ...and ways for a cell to respond to environment

  18. The rest of the demo When the pill is all gone --FIRST, have another swig of that delicious Diet DP! --NEXT try your other lemon slice What’s the difference? What has changed? What can you infer Assertion: pH + one or more histidines + stuff you can think your way through

  19. You might also enjoy • pH • http://www.sumanasinc.com/webcontent/animations/content/influenza.html • http://www.callutheran.edu/BioDev/omm/jmol/ha/ha.html

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