Question

Which one is the rate-limiting step in the oxidation of xenobiotics?

(a) Binding of the substrate to Fe^3+

(b) Electron transfer from NADPH to the above complex

(c) The enzyme-substrate complex combines with a molecule of oxygen forming a ternary complex

(d) Ternary complex gains an electron from the NADPH

The question was posed to me during an interview.

This question is from Drugs Biotransformation topic in section Biotransformation of Drugs of Drug Biotechnology

Answer 1

Correct answer is (b) Electron transfer from NADPH to the above complex

For explanation I would say: The rate-limiting step is the transfer of an electron from NADPH to the complex of substrate and cytochrome 450. The gaining of an electron by cytochrome 450 reduces the Fe^3+ to Fe^2+. This step is considered the rate-limiting step of the oxidation of xenobiotics.