SL MD4

Enzyme inhibitors as medicines

A bit like the antagonists!

• Noradrenaline (neurotransmitter)

• Fits into receptor site

• Electrical impulse sent to heart muscles

• Increases heart beat• Bad for heart

• Antagonist (propanolol) blocks receptor site

• Angiotensin I (substrate)

• Fits into active site of enzyme (ACE)

• Changes it to angiotensin II

• Increases blood pressure• Causes heart attacks and

strokes• ACE inhibitor (captopril)

blocks active site

What causes the high blood pressure?

angiotensin I angiotensin II + dipeptide

ACE - Angiotensin Converting Enzyme

Inactive Active – causes high blood pressure

Need enzyme inhibitor

Following the lead

Venom of Brazilian

Arrowhead Viper can

kill by lowering

blood pressure

It contained

several proteins

which were ACE

inhibitors

But proteins

are digested

in the stomach

Try Ass 9.

Back to the lead compounds ..

Active proteins from snake venom had the amino acid proline at the COOH end of the

chain.

After synthesising hundreds of compounds with proline in …

Not a protein so can be taken

orally!

Try Ass 10.

A bit like the antagonists!

• Noradrenaline (neurotransmitter)

• Fits into receptor site

• Electrical impulse sent to heart muscles

• Increases heart beat• Bad for heart

• Antagonist (propanolol) blocks receptor site

• Angiotensin I (substrate)

• Fits into active site of enzyme (ACE)

• Changes it to angiotensin II

• Increases blood pressure• Causes heart attacks and

strokes• ACE inhibitor (captopril)

blocks active site