Expansion
What happens to Km and Vmax distinguishes them
Expansion
| Type | Binds | Km | Vmax |
|---|---|---|---|
| Competitive | Active site | Increased | Unchanged |
| Non-competitive | Allosteric site | Unchanged | Decreased |
| Uncompetitive | Enzyme-substrate complex only | Decreased | Decreased |
“Competitive can be outcompeted, so Vmax is still reachable.” Adding enough substrate overcomes it, which is exactly why ethanol treats methanol poisoning by competing for alcohol dehydrogenase.
Km is the substrate concentration giving half maximal velocity, and it is inversely related to affinity: a low Km means high affinity.
Clinical examples
- Competitive: methotrexate on dihydrofolate reductase, statins on HMG-CoA reductase, ethanol or fomepizole on alcohol dehydrogenase, allopurinol on xanthine oxidase
- Non-competitive: cyanide on cytochrome oxidase, heavy metals
- Irreversible: aspirin on cyclooxygenase, omeprazole on the proton pump, organophosphates on acetylcholinesterase. These behave like non-competitive inhibition on a Lineweaver-Burk plot
On a Lineweaver-Burk plot (1/V against 1/[S]): competitive inhibitors intersect on the y axis (unchanged Vmax), non-competitive on the x axis (unchanged Km), and uncompetitive lines are parallel.