4.3 Inhibition: reversible and irreversible 4th hour

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4.3 Inhibition reversible and irreversible (4th
hour)

• Objectives
• At the end of the lesson, students would be able
  to
• explain the role and types of inhibitors
• describe competitive inhibitor and non
  competitive inhibitor for reversible inhibition

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4.3 Inhibition
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Inhibition

• Competitive inhibitor
• Noncompetitive inhibitor

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Inhibitors (decrease enzyme activity)
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Illustration of competitive and noncompetitive
inhibitions
Shape of activesite changed
Substrate
(a)
(b)
Active Site
Enzyme
Allosteric Regulatory Molecule
Competitive inhibitoroccupies active site
Allosteric Regulatory Site
(c)
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Inhibition

• Substance that slows down or block enzyme
  activity
• either binds to active site or
• allosteric site
• Competitive inhibitor competes for active site of
  enzyme
• Noncompetitive inhibitor does not binds to the
  active site but the allosteric site

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1. Competitive Inhibitors

• Compete with substrate for same binding site.
• If the inhibitor is sufficiently concentrated, a
  high proportion of the enzymes molecules will
  combine with it
• reaction is slowed down.
• The effect of these inhibitors can be overcome by
  increased substrate concentration
• Eg Malonic acid (malonate) competes with
  succinic acid (succinate), which is a substrate,
  for the active site on the enzyme succinic
  dehydrogenase (succinate dehydrogenase).

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1. Competitive Inhibitors

• Increase in concentration of substrate will
  reduce effect of inhibitor.
• when substrate concentration is higher, the
  chance of substrate occupying active sites are
  higher

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2. Noncompetitive Inhibitors

• Bear no resemblance to substrate molecule
• Do not bind to the active site
• Bind to the allosteric site
• Change shape of the active site so that enzyme
  can no longer accommodate substrate

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2. Noncompetitive Inhibitors

• Increase in concentration of substrate will not
  reduce effect of inhibitor.
• Eg DDT, many antibiotics,

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Reversible inhibition (Competitive inhibition)

• isoleucine (noncompetitive inhibitor) competes
  with threonine to bind enzyme threonine
  dehydratase.

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Irreversible inhibition (Noncompetitive
inhibition)

• Molecule attaches permanently to the active site
  of the enzyme
• enzymes become spoilt (useless)
• no possibility of a normal substrate to bind to
  the active sites of the enzyme.
• Both substrate and inhibitor do not compete for
  the active site.
• Eg natural toxins, pesticides, cyanide and heavy
  metal ions (Hg, Ag, arsenic).

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Irreversible inhibition
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What irreversible inhibitors do to the enzyme?

• Arsenic and iodoasetic acid
• formed permanent bond with sulphidril (-SH) group
  on enzyme, caused denaturizing of enzyme

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How nerve gases and carbon monoxide work?

• Mitochondrion
• where ATP are produced
• Nerve gases and carbon monoxide block electron
  flow from cyctochrome to oxygen
• As a result ATP is not produced

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Note where the cytochromes are located
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Another example Nerve gas DFP designed for use
in warfare

• DFP combines with the amino acid serine at the
  active site of enzyme acetylcholinesterase.
• which functions to deactivate acetylcholine
• Result acetylcholine accumulates and nerve
  impulses cannot be stopped
• prolong muscle contraction
• Paralysis occurs, death may be the result
• Parathion (insecticides) have similar effect.

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