Question: how many chemicle reactions exist that involve cytochromes P450?

  1. Hi jgiumelli,
    At the moment and as far as we know, there are apparently about 60 different kinds of chemical reactions/transformations that P450s can mediate (there could be more – new P450s are being found all the time, so its possible that another kind of reaction they can do will be found as well).

    The most common one is called ‘hydrocarbon hydroxylation’ – this means that the P450 takes a carbon-hydrogen bond (C-H) and inserts an oxygen atom (O) that it has taken from molecular oxygen (O2) into the C-H bond, to form C-O-H. The OH part is called a ‘hydroxyl group’, and a ‘hydrocarbon’ is a chemical made of C and H – so the name ‘hydrocarbon hydroxylation’ describes the formation of C-O-H from C-H.
    Another related one is called ‘heteroatom oxidation’. ‘Organic compounds’ are compounds that are made up of carbon and hydrogen, so ‘heteroatom’ is any other type of atom other than C or H. P450s can add oxygen atoms to heteroatoms like nitrogen (N) and sulfur (S), so P450 can form N=O from N, and S=O from S (the = are double bonds).

    Its a bit difficult to explain and to understand other, more complicated reaction types if you haven’t learnt much about organic chemistry yet. If you are interested in this sort of thing then you should definitely continue studying chemistry when you get to Year 11 and 12. By the way, what Grade/Year of school are you in now? 🙂

    If you are actually asking how many different processes in nature involve P450s, then the short answer is: no one really knows for sure! There are thousands of P450s known and more are being found all the time. We currently know the natural function for some of them but not for others (for some of them, we know that they can mediate certain kinds of reactions on certain substrates, but we don’t know what their function is in nature). LOTS of different people work with P450s to try to figure things like this out.

    To give you some examples, P450s are involved in many processes such as the formation of fatty acids, steroids, and other types of compounds in animals, plants, fungi, and bacteria (including steroid hormones in humans, and some vitamins in bacteria); the formation of pheromones in insects (this is one thing I have been studying); the break-down of compounds by bacteria for energy (another thing I have been studying); the break-down of insecticides by insects and plants (one way insects become resistant to particular chemicals); and the break-down/activation of foreign substances (‘xenobiotic metabolism’; ‘xenobiotic’ means foreign substance) in mammals (there are MANY other things).

    In humans, several P450s that are found in the liver are involved in xenobiotic metabolism. They are responsible for oxidising (adding oxygen to) the drugs that we take (such as paracetamol) once the drugs have exerted their effect in the body, to make them more water-soluble so that our bodies can remove them in our urine.
    Sometimes, a drug is taken in a form called a ‘prodrug’ and needs to be activated inside our body to the active drug form. P450s can be involved in this drug activation, and an example of a prodrug that needs such activation is codeine. A P450 oxidises codeine to form morphine inside the body (morphine is the active pain killer). Sometimes, there are certain P450s that not everyone has in their body – the one that activates codeine is one of the ones that is commonly missing. So there are some people who can take lots of codeine but who won’t really ever get the pain-killing benefits of its active form!
    Sometimes, a P450 oxidising a chemical makes it more dangerous. An example of this is a compound called aphlatoxin, which is found in mouldy peanuts (so don’t ever eat mouldy peanuts!). Another example is something called benzo[a]pyrene – this compound is found as a part of soot (burnt stuff) and can be oxidised by a P450 to a form that can interact with your DNA and cause cancer. This is one reason you shouldn’t really eat burnt food a lot (at all if you can avoid it) – there could be compounds like this formed when your food has burnt a lot, and which can become very dangerous for you after your food has been digested and metabolised (particularly if you keep eating burnt things a lot – like lots of burnt toast).

    jgiumelli, I hope I have managed to actually tell you what you wanted to know, somewhere in this enormous answer! 🙂

    PS. If anyone is interested, there are 57 P450s found in humans.

    0

Comments