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Solutions For An Introduction to Medicinal Chemistry Chapter 3 Problem 5Q

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Solution 1

Michaelis-Menten Kinetics is a model that is best known for the kinetics of enzymes. It is the relation between the reaction rate, V, and substrate concentration, [S]. It is denoted by the following equation, which is as follows:

Where, V represent the rate of reaction, [S] is the substrate concentration, Vmax is the reaction rate that is maximum and Km is Constant (Michaelis). Km is the concentration od substrate at which, the reaction is half of its maximum velocity.

Lineweaver-Burk equation is a derivative of the Michaelis-Menten equation. It is a relation between 1/V and 1/[S]. It is denoted by the following equation as follows:

The data given in the question is of [S] and the corresponding V readings. From that 1/V and 1/[S] could be calculated easily, and one would arrive at the following data table as follows:

[S] (mol L-1)

1/[S]

V (mol L-1 s-1)

1/V

0.05

20

2.86

0.35

0.10

10

5.15

0.19

0.25

4

11.1

0.09

0.50

2

14.1

0.07

1.00

1

14.5

0.06

Plotting a Michaelis-Menten plot (V vs [S]) is as follows:

Picture 2

Figure: Michaelis Menten plot depicting V vs [S].

It can be seen from the plot, the Vmax can be observed to be approximately equal to 14.5 mol L-1 s-1 (moles per liter per seconds) and the Km (corresponding to the Vmax/2) is approximately equal to 0.20mol L-1.

The Lineweaver-Burk plot is shown below as follows (1/V vs 1/[S]):

Picture 3

Figure: Lineweaver-Burk plot depicting 1/Vmax vs 1/[S].

Here, the plot intersecting at y-axis gives 1/Vmax and the point, where the plot intersects at x-axis gives -1/Km. Here, 1/Vmax is 0.045; therefore, Vmax is 22.2mol L-1 s-1. The value of -1/Km is -1.2; therefore, Km is 0.83mol L-1.

Compared with the Michaelis-Menten plot, the Lineweaver-Burk plot gives a highly unreliable estimation of the values for Km and Vmax. The reason behind this is, the use of double reciprocal variables used in the Lineweaver-Burk equation, which totally distorts the error distribution structure of the data.

Therefore, it can be used for accurate estimation of Km and Vmax; however, it can swiftly give an estimation of the nature of inhibition of the reaction. The reactions could be competitive, non-competitive, and uncompetitive.

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