BIOL213 Lecture Notes - Lecture 17: Aromatic Amino Acids, Competitive Inhibition, Dihydrofolic Acid
Lecture 17 – Enzyme Kinetics 2
Enzyme Inhibition:
• The rate at which an enzyme-catalysed reaction occurs is an intrinsic property of
each enzyme. Rate is subject to [S] and [E]
• Enzyme inhibitors can interfere with catalysis, thus slowing
or stopping enzymatic reactions.
• Enzyme inhibitors are among some of the most important pharmaceutical agents
known.
• Inhibitors can bind reversible or irreversibly.
• They often coexist with enzymes and help in regulation.
• Inhibitors may be the product of the reaction pathway (feedback inhibition)
• Includes metabolites, drugs, toxins and substrate analogues.
Importance of enzyme inhibition:
• Inhibitors regulate metabolic pathways —> this is an important physiological
process.
• Inhibition allows us to determine information abut enzyme mechanisms and
metabolic pathways.
• Inhibitors provide information, diagnosis and treatment of illnesses/diseases
• Methotrexate is an example of an enzyme inhibitor - it is used as a chemotherapy
drug. It is similar to the compound dihydrofolate. Methotrexate inhibits the
enzyme dihydrofolate reductase which is needed for the synthesis of DNA
precursors in cells. This drug affects both cancerous and non-cancerous cells that
divide and replicate very rapidly as well (hair cells, germ cells).
• Glyphosate: a broad-spectrum herbicide with inhibits an enzyme that catalyses the
synthesis of aromatic amino acids. Glyphosate is listed as a possible carcinogen.
• Organophosphate: the basis of many pesticides, herbicides and nerve agents. It
irreversibly inhibits the enzyme acetylcholinesterase (AChE) which clears
synaptic clefts of the neurotransmierr acetylcholine to promotor
neurotransmission.
Reversible inhibition:
• Involves non-covalent binding of an inhibitor to the enzyme
• Three different mechanisms by which they reduce enzyme activity:
-Competitive inhibition
-Uncompetitive inhibition
-Mixed inhibition
• In non-competitive inhibition, the shape of the enzyme is changed by something
binding to it (but not to the active site).
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Lecture 17 – Enzyme Kinetics 2
Competitive inhibition:
• A competitive inhibitor competes with the substrate for the active site of
the enzyme. It is structurally similar to the substrate so may form an EI complex.
This can be overcome by increasing [S].
• Cases of methanol poisoning can be treated by administering ethanol, as this
competes with the methanol for binding of the enzyme alcohol dehydrogenase. It
therefore prevents the formation of formaldehyde and formic acid in the body,
which is very toxic.
• A competitive inhibitor increases Km but does not change Vmax (as this is the
ability of the enzyme to convert the substrate to the product- it just needs need
more substrate for this conversion to occur)
Uncompetitive inhibition:
• Binds at a site distinct from the active site
• It only binds to the ES complex
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