PHSC1212 Biochemistry - Lecture 8: Michaelis-Menten Kinetics pt 2

Michaelis-Menten enzyme kinetic model

a mathematical model that describes enzyme-catalyzed reaction rates

Substrate binds to enzyme forming intermediate enzyme substrate complex that facilitates conversion of substrate to product

What happens in the Michaelis-Menten enzyme kinetic model? (E + S <> ES > E + P)

Enzyme substrate complex formation

stabilizes the transition state and facilitates conversion of the substrate (S) to the product (P)

Most reactions are reversible

What fact does the reaction in the Michaelis-Menten enzyme kinetic model ignore?

Initial velocity

the reaction rate at the very beginning of a reaction, before a significant amount of substrate has been converted to product; means reverse reaction has not yet occurred

Steady state assumption

idea that ES formation rate is equal to ES degradation rate; that ES concentration remains constant over time

Simplifies binding and catalytic processes into one

What is the significance of the steady state assumption?

Clean rate vs substrate concentration relationship

What is achieved by simplifying the binding and catalytic processes into a single one?

Km

a constant that is characteristic of the enzyme and the substrate under specific conditions; reflects affinity of enzy,e for substrate and catalytic turnover of substrate to product

Michaelis constant

What does Km represent?

Michaelis-Menten Equation

describes the relationship between reaction rate and substrate concentration

Vmax

the maximum velocity the reaction can reach; reached when all enzymes are saturated with substrate

When all enzymes are saturated with substrate

When is Vmax reached?

1/2Vmax

What does Km, a substrate concentration, correspond to?

Enzyme concentration

What is Vmax directly proportional to?

Becomes zero order

What happens to the reaction when Vmax is reached?

Metabolism by liver enzymes

What do Michaelis-Menten kinetics describe in relation to drugs?

Km and Vmax

two important parameters that determine drug clearance by liver enzymes

Each drug-enzyme pair

What are Km and Vmax specific to?

Drug clearance

used to determine the appropriate dose to achieve a desired plasma drug concentration

Linear pharmacokinetics

What do lower doses exhibit?

Double plasma concentration

What does doubling a dose do?

Plasma concentration is disproportionately increased to the dose

What happens at higher doses where the drug metabolism has changed from first order to zero order?

In linear range

Where are most drugs dosed in pharmacokinetics?

Much larger increase in concentration

At a higher steady state concentration, the same change in dose can produce what?

1/Vmax

In a Lineweaver-Burk plot, what is the y-intercept?

Y intercept

In a Lineweaver-Burk plot, what is the 1/Vmax?

-1/Km

In a Lineweaver-Burk plot, what is the x-intercept?

X intercept

In a Lineweaver-Burk plot, what is the -1/Km?