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  <head>
    <title>087-02 Protein structure, folding, enzyme catalysis, kinetics, and inhibition</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Protein structure, folding, enzymes, and kinetics">
      <outline text="Levels of protein structure">
        <outline text="Primary: sequence plus covalent linkages">
          <outline text="One substitution can change charge or stability"/>
          <outline text="Loss, toxic gain, or no effect"/>
        </outline>
        <outline text="Processing removes signals, splits precursors"/>
        <outline text="Secondary: backbone hydrogen bonds">
          <outline text="Alpha helices and beta sheets"/>
          <outline text="Proline disrupts helices, glycine flexible"/>
        </outline>
        <outline text="Tertiary: hydrophobic interior, polar surface"/>
        <outline text="Quaternary: subunits enable cooperativity"/>
      </outline>
      <outline text="Dynamics and allostery">
        <outline text="Proteins fluctuate among conformations"/>
        <outline text="Induced fit and conformational selection"/>
        <outline text="Allostery couples distant sites"/>
      </outline>
      <outline text="Folding and misfolding">
        <outline text="Folding often begins during translation"/>
        <outline text="Chaperones prevent aggregation">
          <outline text="Do not encode final structure"/>
        </outline>
        <outline text="Disulfides, glycosylation, assembly, cofactors"/>
        <outline text="Quality control retains, refolds, degrades, signals"/>
        <outline text="Denaturation spares peptide bonds">
          <outline text="Exposed hydrophobic surfaces aggregate"/>
        </outline>
        <outline text="Amyloid: cross-beta fibrils disrupt tissue"/>
      </outline>
      <outline text="Catalysis and energetics">
        <outline text="Transition state stabilised over ground state"/>
        <outline text="Acid-base, covalent, metal, proximity, strain"/>
        <outline text="Rates change both ways, equilibrium unchanged"/>
        <outline text="High barrier makes favourable reactions slow"/>
        <outline text="Coupling and product removal keep direction"/>
        <outline text="Active sites distinguish stereoisomers"/>
        <outline text="Isoenzymes: same reaction, different tissues"/>
      </outline>
      <outline text="Michaelis-Menten kinetics">
        <outline text="Complex forms, then proceeds to product"/>
        <outline text="Maximum velocity tracks total active enzyme"/>
        <outline text="Km: substrate giving half maximum velocity">
          <outline text="Approximates, but is not, affinity"/>
        </outline>
        <outline text="Low substrate: first order"/>
        <outline text="High substrate: zero order in substrate"/>
        <outline text="Turnover number over Km measures efficiency"/>
        <outline text="Assumes initial rate and steady state"/>
        <outline text="Nonlinear fitting over reciprocal plots"/>
      </outline>
      <outline text="Inhibition and flux">
        <outline text="Competitive: apparent Km up, Vmax unchanged"/>
        <outline text="Uncompetitive: both lowered"/>
        <outline text="Pure noncompetitive: Vmax lowered only"/>
        <outline text="Mixed inhibition is more common"/>
        <outline text="Irreversible inhibition depends on time"/>
        <outline text="Mechanism-based inhibitors inactivate enzyme"/>
        <outline text="Product inhibition and near-equilibrium enzymes"/>
        <outline text="Sequential versus ping-pong mechanisms"/>
      </outline>
      <outline text="Cooperativity and conditions">
        <outline text="Interacting subunits give sigmoidal curves"/>
        <outline text="Hill coefficient is not site number"/>
        <outline text="pH profile reflects many ionisable groups"/>
        <outline text="Heat accelerates, then destabilises"/>
        <outline text="Metal ions and organic coenzymes">
          <outline text="Apoenzyme inactive, holoenzyme active"/>
          <outline text="Prosthetic groups versus cosubstrates"/>
        </outline>
      </outline>
      <outline text="Zymogens, assays, and methods">
        <outline text="Zymogens: safe storage, amplifying cascades">
          <outline text="Premature activation injures tissue"/>
          <outline text="Activation effectively irreversible"/>
        </outline>
        <outline text="Assays infer amount from catalytic activity">
          <outline text="Leakage, synthesis, obstruction, clearance"/>
        </outline>
        <outline text="Each structural method has limits"/>
        <outline text="Find the step controlling flux in cells"/>
      </outline>
    </outline>
  </body>
</opml>
