As living organisms developed in complexity and their diets expanded to include many types of plants and animals, it was clearly necessary to evolve a system that would protect an organism from food toxins. This process was probably greatly accelerated by the evolution of land animals from their sea-going ancestors. Diets rich in plant material led to the consumption of high numbers of lipophilic agents with long half-l ives, including many aromatic- based compounds. To counter this, it has been suggested that plants evolved chemical defence agents like toxic alkaloids to avoid being eaten. In response, animals probably developed enzymes such as CYP2D6 to metabolize the alkaloids.Aside from direct lipophilic toxins, more long-term threats to animals in this regard would be the large number of plant hormonelike chemicals, such as phytoestrogens. Animals and humans can have enough problems regulating their own hormone levels to ensure timely and appropriate reproduction and maintenance of reproductive tracts, without exogenous hormones deranging function, just because the organism prefers a diet rich in hormone- l aden plants. It is now clear that oestrogen receptors will bind and function in response to a wide variety of chemicals. This is mainly because large numbers of molecules have an aromatized ring in a similar orientation to a steroid. Regarding diet, there are so many oestrogens and other female hormones in some foods that diet alone has been successfully used to control the menopause in women as an alternative to drug therapy. There are commercial sources of plant oestrogens that are sufficiently potent to be marketed as human breast size enhancers that actually work. It is also clear that long-term exposure to inappropriate hormone levels can lead to cancer in vulnerable tissues such as the endometrium, breasts and ovaries. CYPs are a major defence against such unwanted molecules and they actively protect us from exogenous hormone-like molecules. Interestingly, the fact that plant phytoestrogen breast enhancers and other hormone ‘mimics ’ do exert effects in humans indicates that these agents partially thwart CYP systems, as they are not easy to metabolize and inactivate rapidly enough to prevent interference in human hormone balances.
As has been mentioned, plants synthesize many protective toxin-rike agents, but in a harsh environment, to be able to consume such plants without toxicity provides an animal with a significant advantage in its survival prospects. CYPs have also evolved to protect us from such molecules, such as coumarin anticoagulants in some plants. If these cannot be quickly rendered safe and eliminated, severe haemorrhaging can result. The evolutionary ‘ arms race’ between animals, plants and fungi is fiendishly inventive, as agents such as mycotoxins can use our own CYPs to cause lethal toxicity and carcinogenicity.Figure 2.2 illustrates the varying roles of CYPs in living systems.
Figure 2.2 Various functions of biotransformational enzymes, from assembly of endogenous steroids, modulation of various biological processes as well as the clearance of drugs, toxins and endogenous steroids
