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Friday, August 29, 2008

Xenobiotic metabolism enzymes : an attempt at an explanation

This is an attempt to explain what are often refered to as the 'xenobiotic enzymes' or 'drug metabolizing enzymes' (amongst other hard to define names) . These are the cell enzymes that often mostly deal with 'external' chemicals that get into the bloodstream (especially drugs). Usually they are most abundant in the liver (hepatic enzymes) but they can be present anywhere.

They are often classed as phase1/phase2 (biotransformation) enzymes.

Phase1 is the oxidizing layer (the 'non-synthetic reaction' enzymes) (they also do other things, such as reduction)
the main family of phase1 (the heavy duty ones) are the CYP450 family. The FMO family are another phase1 enzyme.

The phase2 enzymes are the 'conjugation reaction enzymes'. They add something to the chemical to completely neutralize it. for instance a sulfur molecule. The main phase2 enzyme reactions are glucuronidation, sulfation, methylation and glutathione, acetylation, and amino acid conjugation. Both phases aren't always needed to detoxify something. For instance trimethylamine only needs to be oxidized by FMO3.

Most of these enzymes DNA can be increasingly switched on or off by chemicals. This is known as induction or inhibition. For instance a compound in grapefruit juice can inhibit many of the CYP450 enzymes. FMO is probably still taught as being uninducible/uninhibitable, but a study has shown a compound in cruciferous vegetables can inhibit FMO.

Everyones 'maximum' amount of of each enzyme varies in general. Since these enzymes often activate or detoxify drugs, they can often explain why someone reacts badly to certain medicines. Researchers are trying to understand these reactions through the science of pharmacogenetics

These enzymes also alter a lot of other chemicals in the body. for instance, detoxifying/activating hormones, neurotransmitters etc ('endogenous substrates').

keywords:
induction
substrate
inhibition
CYP450
phase1/phase2
drug metabolizing enzymes
endogenous/exogonous


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