Biochemical individuality: an article by Dr Michael Murray ND

The phrase "one man's meat is another man's poison" perfectly sums up how an individual could potentially react to drugs or herbs or other external or internally produced metabolites. If someone is sub-normal in a certain detox/activation enzyme, they may react very badly to something supposedly good for them.

Dr Michael Murray ND is one of the most respected natural therapists. In this article, he explains how the likes of drugs should be 'tailor-made' for each individual, because our detoxification/activation enzymes often vary greatly. At the moment drugs are designed as if we will all have the same metabolizing capability. This article is of interest in particular because it focuses on the main family of the 'phase 1'/'nonsynthetic reaction' enzymes, the cytochrome P450 (CYP450) family of enzymes. The flavin mono-oxygenase family (of which there are currently 6 different types known) are another of the phase1/nonsynthetic enzymes, but the CYP450 enzymes are regarded as the heavy duty ones, especially CYP3A4.

http://www.doctormurray.com/newsletter/07-19-2006.htm

More will be written about these enzymes and the other main detoxification enzymes over the weeks, in an effort to help us all learn about them.

keywords:
cytochrome P450, CYP450, CYP3A4
induction, inhibition, substrate
phase1 (nonsynthetic), phase 2 (synthetic)

Quotes:

One of the major determinants of our nutrigenomic profile is a family of perhaps one hundred enzymes known as the cytochrome P450 enzymes. These enzymes play a critical role in detoxifying drugs, cancer-causing compounds, and hormones. Generally, each enzyme is designed to metabolize certain types of chemicals, but there is also a lot of overlap among the P450 family. This “back-up system” ensures that your liver is usually able to detoxify your body efficiently...

...The activity of and interplay between Phase I and Phase II reactions is probably the single most important factor that determines our biochemical individuality. Differences in the P450 enzymes can explain why some people can smoke without developing lung cancer and why certain individuals are more susceptible to the harmful effects of pesticides and other toxic chemicals...

...The study examined the association between heart attack incidence.1 Unlike other studies looking into this association the researchers also measured the activity of the liver enzyme that detoxifies caffeine - cytochrome P450 1A2 (CYP1A2). When the researchers divided the group according to whether they possessed a form of this enzyme that quickly metabolizes caffeine (CYP1A2*1A) or slowly metabolized caffeine (CYP1A2*1F) suddenly the picture on the impact of caffeine intake became very clear. As can be seen from Table 1, those with the rapid caffeine breakdown actually decrease their risk of a heart attack by drinking coffee, while slow caffeine metabolizers actually dramatically increase their risk! Drinking four cups a day of coffee was associated with a 17% decrease risk in fast metabolizers and a 260% increased risk in slow metabolizers...

random links:

nutrigenomics research
http://www.medicine.iupui.edu/flockhart/table.htm