A note on P450

Written by Kamal Patel
Last Updated:

Many times when on this site, when studying up on pharmacodynamics and enzymology, you will see some reference to 'P450' or 'CYP---' (in which the dashes are replaced by numbers/letters.

This is the almighty 'liver detoxification', in part. 'P450' is a term denoted to a family of 60+ enzymes that are all similar in function but unique. The name 'P450' (usually preceded by cytochrome) is due to these compounds causing a spike in light refraction at 450nm.

These enzymes are responsible for most xenobiotics ('strange to life', compounds not normally ingested). If something has evolved with us over time (vitamin C, ethanol, protein) then it might have its own special enzyme pathway in the body (alcohol dehydrogenase for example). If it is a new compound (such as acetominophen) or is found in plants not commonly consumed by humans past, then it is subject to the P450 system.

P450 enzymes are relatively Non-specific. Hence why they can accomodate so many different substrates.

There are also two phases to them. Phase I detoxification and Phase II detoxification (you may have heard of these before). Phase I is also called 'activation' and Phase II 'conjugation', in which the first phase punches a functional group onto a xenobiotic and the second tags it with a large molecule so the compound can be excreted.

As an example, the liver is a bar. You are the xenobiotic. Phase I enzymes are the drunken assholes who yell at and antagonize you to assault them, and Phase II enzymes are the cops that escort you away. If you are relatively calm (inert) you cannot be tagged for removal, however, if you go to the bar reactive, you can get tagged immediately.

(Note: P450s are actually located everywhere in the body, but just mostly in the liver)

The CYP most commonly seen refers to 'CYtochrome P'. The three digits afterwards just indicate the molecule. There are major ones like CYP2E1 (highly involved in alcohol and fasting metabolism, and acetominophen) and CYP1A2 (also known as aromatase). These are all phase I enzymes.

It would be good to get familiarized with them as soon as possible. In a field such as supplementation where we introduce xenobiotics this frequently, P450 enzymes are a big deal. I will make more blog posts in the future on this topic as well.