Aromatase: a target for cancer treatment

Evolution not only produces families of related species, it also gives new families of related genes and proteins, the latter arising from gene duplication and the slow divergence of the two versions. The largest family of proteins is the cytochrome P450 (Cyt P450) proteins, named because of their colourful appearance, their absorption at 450 nm and lack of any information regarding their function.

These Cyt P450 proteins occur in various forms in virtually every organism. There are often dozens, and in some plant species, there are even hundreds of them. Genome studies have revealed, for example, that the honeybee has 46, humans have 55, and the rice plant has 356 genes for such proteins.¹ 

We now know that these enzymes are all involved in oxidation reactions, using an oxygen molecule bound to iron at the centre of their haem cofactor. (A cofactor is the non-protein part of the enzyme which is essential for the catalytic activity of the enzyme.) And since they only use one of the oxygen atoms in the oxygen molecule as an electron acceptor, which ends up in a water molecule, they are also known as mono-oxygenases. The other oxygen atom is used by the enzyme to do some chemistry. There are so many different Cyt P450 proteins because there are so many things that enzymes can do with this spare oxygen atom. 

The key areas in which these oxygenases are active are in hormone synthesis, the hydroxylation of fatty acids, and the degradation of foreign organic molecules, which has important implications for the fate of drugs in the body. They also serve as models for fundamental studies into biophysical phenomena such as electron transfer in proteins. Here we focus on their role in hormone synthesis.