b l o g o f p a r a g

Promiscuous enzymes

Cytochrome P450 (CYP) are the enzymes, mostly in liver that are responsible for breaking down all the foreign chemicals that get inside the body. They take out all foreign chemicals from the bloodstream as it passes through the liver. There are many different isoforms of this enzyme. One of them, 2E1 is responsible for metabolising alcohol. The same isoform is responsible for metabolising drugs like tylenol. Hence, the warning on the bottle about not taking it with alcoholic drinks. Other isoforms also show this very broad range of substrates that they metabolise.

Grapefruit juice is an inhibitor of isoforms 3A4 and 3A5. Patients who are taking drugs (e.g. lipitor, cardiazem) that are metabolised by these isoforms are told to avoid Grapefruit juice to avoid side effects caused by high levels of drug reached because they don't get metabolised.

Conversely, certain drugs (e.g. modafinil induces CYP3A4) can induce CYP450 enzymes causing rapid metabolism of other drugs making them ineffective. Cytochrome P450 metabolism is a topic of huge interest in drug development to ensure the effectiveness of the drugs while minimising side effects and drug-drug interactions.

Usually, enzymes are very specific about what substrate they process, but, Cytochrome P450 are inherently promiscuous. They have very floppy and hydrophobic active sites to accomodate a variety of substrates. This promiscuity allows them to catch any hydrophobic molecules (mostly drugs and other chemicals). Then, it pumps oxygen into those molecules to oxidise them and make them more hydrophilic (water soluble) so that they can be excreted out of the body quickly.