W29 L2 - Enzyme Inhibition and Measurement

Flashcards covering types of enzyme inhibition and how to measure the strength of inhibitors, based on a lecture transcript.

What does 'Vmax app' typically indicate in the context of enzyme kinetics?

It indicates the Vmax (maximum reaction rate) in the presence of an inhibitor.

What does KI (or KIC) stand for, and what does it represent?

KI (or KIC) stands for the dissociation constant for the inhibitor, specifically the competitive inhibitor; it represents how well the inhibitor binds to the enzyme.

What does a small KIC indicate about the effectiveness of an inhibitor?

A small KIC indicates that the inhibitor binds strongly to the enzyme and is a good inhibitor.

What is the relationship between KIC (dissociation constant) and KB (binding constant)?

KB (binding constant) is the inverse of KIC (dissociation constant), i.e., KB = 1/KIC.

What is the inhibitor coefficient, alpha (α), and how is it defined for a competitive inhibitor (αc)?

The inhibitor coefficient (α) indicates how much the inhibitor affects enzyme kinetics.

For a competitive inhibitor (αc), it's defined as 1 + [Inhibitor Concentration] / KIC.

In the presence of a competitive inhibitor, how are Vmax and Km affected?

Vmax remains the same, and Km increases (goes up).

What is a Dixon plot used for, and what parameters are plotted

A Dixon plot is a graphical tool used to determine the inhibition constant (Ki) for reversible enzyme inhibitors.

Useful for distinguishing between different types of enzyme inhibition, such as competitive, non-competitive, and uncompetitive inhibition

It involves plotting the reciprocal of the reaction rate (1/V) against different concentrations of the inhibitor [I] at varying substrate concentrations, allowing for a precise determination of the inhibitor's potency.

On a Dixon plot, what does the x-intercept represent?

The x-intercept represents -KIC

For an uncompetitive inhibitor, what does KIU represent?

KIU represents the dissociation constant for the uncompetitive inhibitor.

How is the inhibitor coefficient alpha (αu) defined for an uncompetitive inhibitor?

Alpha (αu) is defined exactly the same as for a competitive inhibitor: 1 + [Inhibitor Concentration] / KIU.

In the presence of an uncompetitive inhibitor, how are Vmax and Km affected?

Both Vmax and Km decrease (go down).

For an uncompetitive inhibitor Dixon plot, what is plotted on the y-axis?

1 / Vmax app is plotted on the y-axis.

What two dissociation constants are relevant when discussing a mixed inhibitor?

KIC, which represents the competitive component,

KIU, which represents the uncompetitive component.

What is rational drug design?

Rational drug design is a method to develop new drugs based on knowledge of the structure of the enzyme and potential inhibitors, often using computer modeling for docking.

What role does the KIC value play in rational drug design?

The KIC value is used to assess the strength of potential drug candidates (lead compounds); a smaller KIC indicates a stronger binding affinity and a better drug candidate.