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Tuesday, June 17, 2008

Drug metabolizing enzymes : FMO3 is one such enzyme

These sort of educational posts will be ongoing, and as I learn along the way, I'll pass it along to you.

Drug-metabolizing enzymes

This seems to be a broad 'trade' term for a group of metabolizing enzymes that deals with many chemicals , the FMO family (flavin monooxygenase) being one of the group. There are currently 5 generally accepted FMOs. We will be discussing the enzymes that deal with the metabolism of drugs as well as with many other chemicals, including internally produced hormones, and of external sources, such as the gut and environment airborne chemicals through the skin.

As the process of metabolic detoxification is explained in Wikipedia, "An animal's metabolism can produce harmful substances which it can then make less toxic through oxidation, conjugation and excretion of molecules from cells or tissues. This is called xenobiotic metabolism."

There seem to be 2 main groupings of such enzymes :
1: the 'nonsynthetic reaction' group (oxidation, reduction, hydrolysis, cyclization, and decyclization reactions). The FMO family are part of this group.
2: the 'synthetic reaction' group (the conjugative group, which add something to a 'chemical')

The main purpose of this type of enzyme seems to be to keep the main circulating blood as clear of toxins as possible by altering them into easily excretable non-toxic compounds, and to properly activate chemicals supposed to do some good.

Good explanantion : http://www.merck.com/mmpe/sec20/ch303/ch303e.html

short quick link: http://en.wikipedia.org/wiki/Drug_metabolism
pdf format. Not sure how relevant : http://tools.invitrogen.com/downloads/O-12758DMEGuide_Intro.pdf

As a loose analogy, which may not be totally correct but gives a sense of the concept, regarding drug-metabolizing enzymes:

If you think of theses enzymes as supermarket checkout cashiers, and the 'substrates' are the (fat soluble) shoppers to be processed (turned into water soluble). There are express checkouts and disability checkouts, all designed to make processing the shoppers as efficient as possible. Say the 'express' cashier is the FMO3 enzyme, and not very good. Then a big queue builds up there, but most of the FMO3-substrate shoppers can go join other queues instead, to queue behind people with trolleys. Sadly, unlike most 'substrates', TMA doesnt have another option apart from FMO3.

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