In Michaelis-Menten kinetics, what happens to the reaction rate v when the substrate concentration [S] is much greater than Km?

• A. v becomes independent of [S]
• B. v approaches Vmax and reaction becomes zero-order in [S]
• C. v equals k[S]
• D. v approaches zero

Answer: (B)

When the substrate concentration is much greater than Km, the enzyme becomes saturated because every enzyme molecule has a substrate bound most of the time. In this situation the rate is limited by how quickly the enzyme can convert bound substrate to product, not by how much substrate is around. So the reaction reaches a maximum rate, Vmax, and further increases in substrate do not increase the rate. In other words, the rate becomes independent of [S] and is zero-order with respect to the substrate. This comes from the Michaelis-Menten form v = Vmax [S] / (Km + [S]); with [S] >> Km, the denominator ~ [S], giving v ≈ Vmax. Remember that Vmax depends on the total enzyme concentration (Vmax = kcat [E]t).