Expansion
Km reflects affinity and Vmax reflects capacity
Expansion
- Km: the substrate concentration at half maximal velocity. A low Km means high affinity
- Vmax: the maximum rate when the enzyme is saturated
| Inhibition | Km | Vmax | Overcome by more substrate |
|---|---|---|---|
| Competitive | Increased | Unchanged | Yes |
| Non-competitive | Unchanged | Decreased | No |
| Uncompetitive | Decreased | Decreased | No |
Clinical applications:
- Ethanol competitively inhibits alcohol dehydrogenase, which is why it was used as an antidote in methanol and ethylene glycol poisoning, now largely replaced by fomepizole
- Methotrexate competitively inhibits dihydrofolate reductase, and folinic acid rescue bypasses the block
- Aspirin irreversibly acetylates cyclo-oxygenase, so recovery requires new enzyme synthesis, which in platelets means new platelets
Zero order kinetics occurs when an enzyme is saturated, so a constant amount is metabolised per unit time regardless of concentration. Phenytoin, alcohol and high dose aspirin behave this way, which is why small dose increases cause disproportionate and sometimes toxic rises in level.