Originally Posted by nautica
Xenobiotic Metabolism
Xenobiotic Metabolism (basically drug metabolism, esp. breakdown) is carried out by enzymes, mainly in the liver, but also in the lung, kidneys, GI tract and skin. There are 3 phases in the in xenobiotic metabolism from the initial activation or deactivation to the final transport and clearance.
Phase 1 = functionalism or introducing a polar group to the molecule in order for the drug to be brought into cells and/or organelles.
Phase 2 = conjugation or coupling of a typically polar group to the molecule (the addition of the polar group will later be used in transport)
Phase 3 = Transport or altering localization of the molecule. i.e. Renal or biliary excretion.
Depending on the type of molecule (polar/nonpolar, ect...) the drug may or may not have to enter phase 1, it could start off in phase II, or III for that matter if it is a polar molecule and transportable. As we know, steroids are a class of large mostly non polar molecule, so they must be initiated in phase I.
Cytochrome P450 is the largest superfamily of Phase I enzymes, currently known. P450 has evolved along with humans, mainly for the purpose of endogenous steroid and arachidonic acid metabolism but as man began to partake in drugs, they assumed the role of exogenous drug metabolism and also exogenous steroids.
Fortunately, we also have other types of phase I enzymes such as Alcohol and aldehyde dehydrogenases. As alcohol is introduced into the body, it is brought into the cytosol, mainly in the parenchymal cells of the liver. At this time Alcohol dehydrogenase converts the alchohols to acetic aldehyde, which is perfectly fine. But, then the acetic aldehyde is shunted into the mitochondria, where it is converted to acetic acid, which is toxic. In this case, to the liver. At which time, it does its damage and moves on into Phase II metabolism.
So, at this time it does not appear that there would be a conflict. At least not on a cellular level. Right? Not neccessarily. For high levels of alcohol intake or alcoholics the Cytocrome P450 family also contributes to the phase I metabolism of alcohol, which, if you will recall, is what metabolizes steroids in phase I.
It does not appear that there is significant direct conflict in Phase II and III; however, as these drugs move through the metabolic phases they will cause necrosis on a gross scale, which will put an increased burden on the remaining tissues for the clearance of the drugs.
THIS IS A SIDE NOTE BUT IS OF EXTREME CLINICAL SIGNIFICANCE. PHASE I METABOLISM OF ACETAMINOPHEN WILL ACTIVATE 5% OF ACETAMINOPHEN, WHICH WILL ALSO HAVE TO BE CLEARED BYE CYTOCHROME P450. THERE HAVE BEEN NUMEROUS STUDIES SHOWING THE EXTREME DANGERS OF ACETAMINOPHEN BY ITSELF BUT IN RELATION TO ALCOHOL IT IS EVEN MORE SERIOUS AND IF STEROIDS ARE ADDED TO THE MIX IT IS EVEN MORE SERIOUS.
What does all of this mean. Basically, no one knows for sure. There are sooo many factors affecting xenobiotic metabolism: age, diet, health, gender, polymorphisms, species variation (animal testing problems), substrate competitive inhibition, enzyme stabilization or induction, routes of administration, ect......
This makes it also impossible for any one to tell you what will or will not hurt you, specifically. But, what I can tell you is that with each additional "vice" you add into your system you are raising your risk factors and you will be shortening your "natural" life expectancy (what I mean by natural life is excluding accidents, car wrecks, smoking, ect....). So it is up to you what you decide what you do with your life and what you choose to put in your body. But, you need to keep in mind that your view may be different now then it will be when you are 40 or 50 or 60. Who knows maybe if you live to be 70 and you have grand children running around, that might be worth more to you than 5 or 10 years of being JACKED.
BOTTOM LINE: I would suggest that if you are going to do steroids that you keep the 17 alpha-alkylated's to a minimum, although testosterone without any esters or 17 alpha-alkylated's, ect... must also be metabolized by the liver. The only, difference, and I repeat the only difference is the number of passes it takes through the liver. And, yes I know that aromatase converts test to estrogen yadda, yadda yadda, but this is also a "steroid" and at some point it will have to be broken down and removed from the body. And, if you must drink alcohol, then keep it also to a minimum. Don't binge and don't drink every night. And, most importantly, leave the FUCKING ACETAMINIPHEN alone. No matter what, don't take this drug (ibuprophen is also bad but not as bad) for any reason. Especially, if you have a hang over and your body has been clearing alcohol all night (plus the 300 mgs of Dianabol - methandrostenolone - you have built up in your system). Also, if you like to pop a few hydrocodones, while you drink, then just go straight for the oxycotin, at least, then your body will not have to metabolize all of the acetaminophen the government requires to be put into these drugs. But that is another story.
Hope that clears things up.
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