Posted by Larry Hoover on November 23, 2004, at 8:56:11
In reply to Re: How do I know IF I am a slow metabolizer? » Larry Hoover, posted by jasmineneroli on November 23, 2004, at 0:49:24
> Hey Lar!
> EXTREMELY cool link! I think I've found a new obsession! (J/K)
Passion is a lovely thing.
> Well, I think I've discovered the reason why I'm a slow metabolizer of 2C19........oral contraceptive pill use for 5 years in the mid 1970's! (And subsequent contraceptive use in an attempt to mitigate peri-menopause symptoms).
Okay, here's my last 2C19 link:
> Since they inhibit 2C19, do you think it's possible that inhibition of an enzyme for a long period of time by a certain drug or group of drugs (particularly the "old" high dose Oral Contraceptives) permanently effects the enzymes' abiilty to metabolize efficiently, or at all?
No, that's not how it works at all. Your body makes these enzymes anew every day. Think about the cars you see on the highway. Many are new, most are fairly new, some are old, and a few are really old. That's the same sort of population distribution for the enzymes in your body. They "turn over" on a roughly two week cycle (gross generalization), rather than the twenty years for cars, but you get a similar age mix. Inhibition that happened years ago has long since gone away.
> I did notice that a couple of notes on other isoenzymes on the table, stating "irreverseable effect".
Inhibition effects are best explained if I start with how an enzyme is supposed to work. An enzyme binds to a substrate, and sort of stretches the substrate into a new shape by partially reacting with its chemical bonds, or its bonding potential. That allows another molecule or fragment of a molecule to react more readily with the substrate, or for a piece to come off the substrate, or whatever it is that the enzyme promotes. The enzyme reduces the energy required for a chemical reaction to occur. It facilitates a reaction.
An enzyme is specific. Only molecules with the right shape can get into the active site, and get "involved" with the bond stretching that the enzyme specializes in.
Now, to inhibition. Just as a lock on a door, some keys won't go in at all (if you pick randomly off your key ring), but others go in and don't turn the cylinder. It's those molecules that go into the enzyme but don't do anything that inhibit it. While it's occupied like that, a real substrate can't get in. That's called competitive inhibition, and it's the most common kind. It's also possible that inhibition occurs between two competing substrates for the same enzyme. One might take a lot longer time in the enzyme than the other, and that just bogs things down. That's another kind of competitive inhibition, when you take two drugs that have to use the same enzyme.
Irreversible inhibition is a permanent chemical change in the enzyme structure. It can be that a potential substrate for the enzyme is just too reactive with the enzyme's active site, and a true bond forms with the substrate, locking it in place. Or, the chemical change can involve an internal rearrangement of the enzyme itself, changing its shape and thus its activity. An example of an irreversible change in a protein is cooking an egg. You can't uncook it. Back to the lock analogy. The first sort I described in this paragraph would be like breaking a key off in the lock. The second sort would be like putting crazy glue in the lock. The lock's toast.
Your body is constantly producing replacement enzymes, so irreversible inhibition only affects the individual enzyme molecules that got hit by the irreversible inhibitor. Parnate and Nardil are irreversible inhibitors of the enzyme monoamine oxidase, but you have to take them every day because: a) your body is constantly destroying and excreting the inhibiting drug; and b) your body is constantly churning out new molecules of monoamine oxidase.
> I think this theory may well apply to me. It's also interesting to note that I didn't develop any irritable depression until I took O.C.'s ( always had anxiety, tho'). So much so, that I was really hesitant to take them again to help perimenopause. After that experiment with them, and horrible suicidal depression/anxiety, even my GP of the time said " I think I've made you sick, by putting you back on the pill"!
> There has to be a connection between it all.
Your liver function, interacting with the drug effects of the hormones, has got to be at the root of your response.
> For some reason, I'm finding this unravelling process, very therapeutic. I feel like I'm finding answers to "why am I like this?"
...or, perhaps, "what am I like?" It is indeed about your uniqueness. The special way you are.
> and "why do I keep responding so badly with the same S/E's?". It's kinda empowering.
It is, isn't it?
> I just don't want to keep on trying drug after drug and having the same ill-effects. At least I will know which ones I definitely shouldn't try.
> Thanks so very much Larry :).
> Warm wishes, Jas
> Still working on the tryptophan plan.
You're very welcome, Jas.