21.5 Enzyme Inhibition

1
Chapter 21 Enzymes and Vitamins

• 21.5 Enzyme Inhibition
• 21.6 Regulation of Enzyme Activity
• 21.7 Enzyme Cofactors

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Enzyme Inhibition

• Inhibitors
• Are molecules that cause a loss of catalytic
  activity.
• Prevent substrates from fitting into the active
  sites.
• E S ES E P
• E I EI no P

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Reversible Competitive Inhibition

• A competitive inhibitor
• Has a structure like the substrate.
• Competes with the substrate for the active site.
• Has its effect reversed by increasing substrate
  concentration.

4
Noncompetitive Inhibition

• A noncompetitive inhibitor
• Has a structure different than the substrate.
• Distorts the shape of the enzyme, which alters
  the shape of the active site.
• Prevents the binding of the substrate.
• Cannot have its effect reversed by adding more
  substrate.

5
Malonate and Succinate Dehydrogenase

• Malonate
• Is a competitive inhibitor of succinate
  dehydrogenase.
• Has a structure that is similar to succinate.
• Inhibition is reversed by adding succinate.

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Irreversible Inhibition

• Loss of all enzymatic activity
• Toxic substance (irreversible inhibitor) forms a
  covalent bond with an amino acid in the active
  center.
• Prevents the substrate from entering the active
  site.
• Prevents the catalytic activity.
• Examples insecticides and nerve gases inhibit
  the enzyme acetylcholinesterase (needed for nerve
  conduction).

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Irreversible inhibitor DFP (diisopropyl
fluorophosphate)

• DFP forms a covalent bond with the OH group of
  the amino acid serine in the active site of the
  enzyme acetylcholinesterase.
• Acetylcholinesterase is inhibited.
• The transmission of nerve impulses is blocked.
• Paralysis occurs.

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Irreversible Inhibition

• In irreversible inhibition, a substance destroys
  enzyme activity by bonding with R groups at the
  active site.

9
Zymogens

• Zymogens (proenzymes)
• Are inactive forms of enzymes.
• Are activated when one or more peptides are
  removed.
• Such as proinsulin is converted to insulin by
  removing a small peptide chain.

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Digestive Enzymes

• Digestive enzymes are
• Produced as zymogens in one organ and transported
  to another such as the pancreas when needed.
• Activated by removing small peptide sections.

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Allosteric Enzymes

• An allosteric enzyme is an enzyme in a reaction
  sequence that binds a regulator substance.
• A positive regulator enhances the binding of
  substrate and accelerates the rate of reaction.
• A negative regulator prevents the binding of the
  substrate to the active site and slows down the
  rate of reaction.

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Feedback Control

• In feedback control
• A product acts as a negative regulator.
• An end product binds with the first enzyme (E1)
  in a sequence, when sufficient product is present.

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Enzyme Cofactors

• A simple enzyme is an active enzyme that consists
  only of protein.
• Many enzymes are active only when they combine
  with cofactors such as metal ions or small
  molecules.
• A coenzyme is a cofactor that is a small organic
  molecule such as a vitamin.

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Enzyme Cofactors

15
Metal Ions as Cofactors

• Many active enzymes require a metal ion.
• Zn2, a cofactor for carboxypeptidase, stabilizes
  the carbonyl oxygen during the hydrolysis of a
  peptide bond.

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Some Enzymes and Their Cofactors