2.4.9 enzyme inhibition: poisons & medicinal drugs

Question 1

examples of metabolic poisons (toxins) which act as enzyme inhibitors

Answer 1

• cyanide
• snake venom

Question 2

how does cyanide act as an enzyme inhibitor

Answer 2

• potassium cyanide (KCN) inhibits aerobic respiration & catalase
• if ingested, KCN is hydrolysed producing hydrogen cyanide (toxic gas) which can readily dissociate into H+ & CN- ions
• CN- ions bind irreversibly to enzyme found in mitochondria which inhibits final stage of aerobic respiration meaning earlier stages cannot run & aerobic respiration stops

Question 3

how does snake venom act as an enzyme inhibitor

Answer 3

• venom of green mamba snake contains chemical which inhibits enzyme acetylcholinesterase (AChE) which is important at neuromuscular synapses to break down neurotransmitter, acetylcholine (ACh)
• if AChE inhibited, ACh stays attached to receptors on muscle membrane & keeps muscle contracted
• causes paralysis & if muscles involved in breathing are paralysed then victims die from suffocation

Question 4

name some medicinal drugs which act as enzyme inhibitors

Answer 4

• aspirin
• ATPase inhibitors
• ACE inhibitors
• protease inhibitors
• nucleoside reverse transcriptase inhibitors

Question 5

how does aspirin act as enzyme inhibitor

Answer 5

• used for 3000+ years
• 1971: professor john vane/team discovered salicylic acid binds to enzymes which catalyse formation of prostaglandins
• prevents formation of prostaglandins which are cell signalling molecules produced by cells when tissues are infected/damaged
• prostaglandins make nerve cells more sensitive to pain & increase swelling
• aspirin also reduces risk of blood clots forming in blood vessels

Question 6

how does ATPase inhibitors act as enzyme inhibitors

Answer 6

• extracts from purple foxglove leaves
• used to treat heart failure & atrial arrythmia
• chemicals now identified as cardiac glycosides
• inhibit sodium potassium pump in cell membranes of heart-muscle cells & allow more calcium ions to enter cells
• calcium ions increase muscle contractions = strengthens heartbeat

Question 7

how does ACE inhibitors act as enzyme inhibitors

Answer 7

• inhibit angiotensin converting enzyme (ACE) which normally operates in metabolic pathway that ultimately increases your BP

used to:
- lower BP in patients w/ hypertension so cannot take beta blockers
- treat heart failure
- minimise risk of second heart attack/stroke in patients who’ve suffered myocardial infarction

Question 8

how does protease inhibitors act as enzyme inhibitors

Answer 8

(eg. amprenavir, ritonavir)
- used to treat some viral infections

• prevent replication of virus particles within host cells by inhibiting protease enzymes so viral coats can’t be made
• often competitive inhibition

Question 9

how does nucleoside reverse transcriptase inhibitors act as enzyme inhibitors

Answer 9

• many of antiviral drugs (eg. zidovudine, abacavir) to treat HIV-positive patients are these
• inhibit enzymes involved in making DNA using viral RNA as template