Animation: Enzyme Inhibition

1
Animation Enzyme Inhibition

• SBI4U Curriculum expectation
• describe the chemical structure, mechanisms, and
  dynamics of enzymes in cellular metabolism.
• describe technological applications of
• enzyme activity in the food and pharmaceutical
• industries
• SBI3C Curriculum expectation
• investigate, through experimentation, the
• effect of environment on the action of
• enzymes
• Created By Kevin Mills
• http//juang.bst.ntu.edu.tw/BCbasics/Animation.htm
  

2
Substrate
Normal Enzyme Function
Product
Product
Active Site
Enzyme
Allosteric Site
Normal Enzyme Function The substrate attaches to
the enzyme at the active site and is catalyzed to
form a product. Increasing the concentration of
the substrate increases the rate of reaction
until all the active sites are full.
3
Competitive Inhibition
Substrate
Active Site
Enzyme
Allosteric Site

• Competitive Inhibition
• A similar but non-reactive molecule competes for
  and binds to the active site on the enzyme,
  preventing the substrate from binding. No
  reaction takes place.
• Increasing the concentration of the substrate can
  overcome the inhibition.
• Drugs are often competitive inhibitors.

4
Competitive Inhibition

• Example Ethanol is metabolized in the body by
  oxidation to acetaldehyde, which is in turn
  further oxidized to acetic acid by aldehyde
  oxidase enzymes. Normally, the second reaction is
  rapid so that acetaldehyde does not accumulate in
  the body.
• A drug, disulfiram (Antabuse) inhibits the
  aldehyde oxidase which causes the accumulation of
  acetaldehyde with subsequent unpleasant
  side-effects of nausea and vomiting. This drug is
  sometimes used to help people overcome the
  drinking habit.
• http//www.elmhurst.edu/chm/vchembook/573inhibit.
  html

5
Non-competitive Inhibition
Substrate
Active Site
Enzyme
Allosteric Site
Inhibitor

• Non-competitive Inhibition
• Inhibitory molecule binds to inhibition site
  (allosteric site) which changes the active site.
  This prevents the binding of the substrate. No
  reaction takes place.
• Increasing the concentration of the substrate
  does not overcome inhibition.
• Example is feedback inhibition.

6
Non-competitive Inhibition

• If the inhibition is at a place remote from the
  active site, this is called allosteric
  inhibition. Allosteric means "other site" or
  "other structure". The interaction of an
  inhibitor at an allosteric site changes the
  structure of the enzyme so that the active site
  is also changed.
• Since many enzymes contain sulfhydral (-SH),
  alcohol, or acid groups as part of their active
  sites, any chemical which can react with them
  acts as a noncompetitive inhibitor. Heavy metals
  such as Ag, Hg2, Pb2 have strong affinities
  for -SH groups.
• Nerve gases such as diisopropylfluorophosphate
  (DFP) inhibit the active site of acetylcholine
  esterase by reacting with the hydroxyl group of
  serine to make an ester.
• http//www.elmhurst.edu/chm/vchembook/573inhibit.
  html

7
Substrate
Uncompetitive Inhibition
Active Site
Enzyme
Allosteric Site
Inhibitor
Uncompetitive Inhibition Substrate binding to
the enzyme modifies the allosteric site to allow
the inhibitor to bind. This changes the enzyme to
prevent reaction at the active site. Increasing
the concentration of the substrate favours
inhibition.
8
Uncompetitive Inhibition

• The weedkiller Roundup (N-phosphonomethylglycine,
  also known as glyphosate), an uncompetitive
  inhibitor of 3-phosphoshikimate
  3-carboxyvinyltransferase 7, which is believed
  to owe its effectiveness to the huge increases in
  metabolite concentrations that are produced in
  treated plants.
• An example of clinical importance is the use of
  Li ions to treat manic depression, the
  effectiveness of which has been attributed to the
  uncompetitive inhibition of myo-inositol
  monophosphatase by Li.
• http//bip.cnrs-mrs.fr/bip10/leics.htm