Zone 3, cytochrom P450

[mochachippy]

Hi everyone,
I was going through some notes and had a question. It says that Zone 3 in the hepatocyte undertakes drug metabolism. This confuses me however. Doesn't drug metabolism and cytochrom p450 require oxygen? And doesn't Zone 3 receive the least amount of oxygen?
I would appreciate any help!
Thank you,
Amitha

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[Rollo]

Yes, you're correct that it does receive the least amount of oxygen. Yet it still receives some oxygen by which the CYP450 can carry out its oxidative function.

If you think about it, it makes sense then why zone 3 is most susceptible to ischemic injury because if it doesn't receive its critical supply of oxygen, the zone will undergo ischemia > necrosis and the whole pathology you generally see in acute liver failure.

It makes it easier to remember that since CYP450 needs oxygen to detoxify drugs (and it barely receives any under normal conditions), any lack of O2 to zone 3 will have devastating consequences. Hence, zone 3 is most susceptible to ischemic injury.