How do cytochromes work

[ross46]

Hi there, instead of rewriting the whole post again i'm just copying and pasting from my post in the "other drugs" forum as i was told my question was more suited to this section

what does the cytochrome actually do to "metabolise" the drug. i saw something about P450 and de-hydogenase? so in the case of dehydrogenase, it uses another chemical in the body (such as NAD(P)H ) with an electrical charge due to it being one electron short to remove the hydrogen atom? Is it similar to respiration where the iron molecule in the haemoglobin is electrically charged so binds with the oxygen or carbon dioxide atom, essentially creating a new molecule?


In the case of codeine, it says that "Codeine is metabolised by O- and N-demethylation". What is the process there? what chemical in the body can substitute a methyl group? and then where does CYP2D6 come into it? Trying to remember A level chemistry and biology!!

is there a thread that already explains this because i can't be the only one who's asked this. I've tried searching but when you type in codeine and morphine it comes up with loads of random threads, even if you put in "codeine demthylation"

Thanks

 

[serotonin2A]

The reaction mechanisms are reviewed in this paper:

http://pubs.acs.org/doi/full/10.1021/cr020443g

 

[tryp2fun]

The reaction mechanisms are reviewed in this paper:

http://pubs.acs.org/doi/full/10.1021/cr020443g

That paper may be a bit advanced. I don't think that he is worried about the structure of compound 1, whether it is more an Fe(V)-oxo or Fe(IV)-oxo-porphyrin pi radical cation. What P450 does is put oxygen atoms into molecules, usually on carbon atoms, to make them more easily excreted by the kidneys. As a result, it can break bonds between carbon and other atoms, particularly nitrogen and oxygen. Especially if there is a single carbon atom (methyl) on an oxygen or nitrogen, P450 will take it off. P450 is structurally similar to hemoglobin, and both bind O₂, but hemoglobin binds it reversibly. There are (IIRC) 57 P450 genes in the human genome. However, only a few of them are responsible for almost all drug metabolism, 2C9, 3A4 and 2D6 especially. Any particular drug will be mainly metabolized by only one P450.

 

[serotonin2A]

That paper may be a bit advanced. I don't think that he is worried about the structure of compound 1, whether it is more an Fe(V)-oxo or Fe(IV)-oxo-porphyrin pi radical cation. What P450 does is put oxygen atoms into molecules, usually on carbon atoms, to make them more easily excreted by the kidneys. As a result, it can break bonds between carbon and other atoms, particularly nitrogen and oxygen. Especially if there is a single carbon atom (methyl) on an oxygen or nitrogen, P450 will take it off. P450 is structurally similar to hemoglobin, and both bind O₂, but hemoglobin binds it reversibly. There are (IIRC) 57 P450 genes in the human genome. However, only a few of them are responsible for almost all drug metabolism, 2C9, 3A4 and 2D6 especially. Any particular drug will be mainly metabolized by only one P450.

The OP specifically asked "what does the cytochrome actually do to 'metabolise' the drug. i saw something about P450 and de-hydogenase? so in the case of dehydrogenase, it uses another chemical in the body (such as NAD(P)H ) with an electrical charge due to it being one electron short to remove the hydrogen atom? Is it similar to respiration where the iron molecule in the haemoglobin is electrically charged so binds with the oxygen or carbon dioxide atom, essentially creating a new molecule?"

The answer to that question requires looking at the specific reaction mechanism. He already knows that codeine is being O-demethylated, so it doesn't make sense to keep this discussion at the very basic level that you are describing.