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So these enzymes may be involved in blood-brain compounds that interact with them. Naturally occurring barrier permeability, which I addressed in NEXUS 18/03. compounds may also induce or inhibit CYP activity. However, the fact that the highest concentration of CYP isin Compounds including bergamottin, dihydroxy- the liver and small intestine indicates that detoxifying food bergamottin, paradicin-A and naringenin, found in compounds may be the primary goal of these enzymes. _ grapefruit and some other fruits, have been shown to CYP has also been found in the lungs, skin, kidneys, inhibit CYP3A4-mediated metabolism of some drugs, bladder, brain, blood vessels and to a lesser extent in all eading to increased bioavailability and thus the the cells of the body. possibility of overdosing. Because of this risk— Cytochrome P450 enzymes may play an important role — involving CYP3A4—avoiding grapefruit while taking in cancer. Some CYPs may bioactivate pro-carcinogens drugs is often advised. into carcinogens, and some CYPs are involved in the An example of the complexity of all this relates to St removal of carcinogens from the body. ohn's Wort (SJW), a herbal remedy used for depression. Several cancers are known to be hormone sensitive, | Scott and Elmer in 2002 stated that SJW "...illustrates and thus the CYPs involved in, for example, steroid or ow results obtained in vitro may not reflect what retinoic acid metabolism may be involved in appens in vivo. SJW has been found to inhibit several suppression or promotion. of CYP isozymes in vitro, including malignancies. There is also CYP2C9, CYP2D6, and CYP3A4. In vivo, indication that CYPs in the lung may however, SJW appears to be an enzyme lung cancer especially inegaretre. | CYtochrome P450 | een Tha clinical findings my smokers. enzymes may play be explained by a constituent of SJW, CYP is known to change as we . hyperforin, that affects the production progress from infancy to old age. For an Important of metabolizing enzymes. Hyperforin example, CYPIA2 is not expressed in role In cancer. appears to bind to a nuclear receptor neonates, making them susceptible to called the pregnane X receptor, toxicity from drugs and caffeine, Some CYPs may increasing the expression of CYP3A4. which is also metabolised by CYPIA2. bioactivate This activity, which is not observed in Probably we are all better off without Q vitro, leads to increased CYP3A4 caffeine, but it's important to keep pro-carcinogens availability and subsequent increased very young children away from into carcinogens, metabolism of drugs acting as substrates for CYP3A4... Drug interactions with St John's wor cola, tea or coffee. Some CYPs_ are found and some CYPs throughout the body, e.g., CYP51, are involved in mediated by CYP3A4 could be while others are found in just one ethal."! specific tissue. CYP11B2 has the removal of Readers of NEXUS are aware, o been found only in the carcinogens from course, of Big Pharma's desire to glomerulosa zone of the adrenal eliminate natural remedies, bu the body. his article indicates the potentia danger of taking several things— erbs or drugs—at the same ime. gland. CYP-Mediated Drug Interactions Let's examine some specific, CYP46, which appears to rid the important CYP enzymes. Chronic brain of excess cholesterol, and ethanol consumption has been found to induce CYP2EI_ —-CYP51 are involved in cholesterol metabolism. CYP26 is and may increase the likelihood of toxicity. CYP3A4 involved in retinoic acid metabolism. CYP19A catalyses makes up about 30 per cent of all CYP in the liver and androgens into oestrogens. CYP7 is involved in bile about 70 per cent of small intestinal CYP. This large acid synthesis. CYP5 is involved in thromboxane family of enzymes metabolises more drugs than any — synthesis. CYP8 is involved in prostacyclin synthesis. other CYP450, but it also metabolises steroid CYPIA is involved in bilirubin metabolism. The CYP4 hormones, cholesterol and vitamin D. Now if someone __ family is involved in metabolism of fatty acids, including is taking several drugs, potentially serious problems arachidonic acid. may arise, as follows. If one drug inhibits the CYP- Some of the CYP2 family is found in high amounts in mediated metabolism of another drug, the second drug _ the nasal mucosa, and some of what they do is to may reach a toxic level in the body. This is why _ interact with and detoxify cigarette smoke. Here again pharmacists and physicians first ask for the complete | we see how these microscopic enzymes may account for list of drugs that a person may be taking. how some people are profoundly affected by the smell However, CYPs do not know the origin of the — of cigarette smoke. or enzymes may play an important role in cancer. bioactivate pro-carcinogens into carcinogens, and some CYPs carcinogens from the body. CYP-Mediated Drug Interactions 40 * NEXUS JUNE - JULY 2012 Cytochrome P450 Some CYPs may are involved in the removal of www.nexusmagazine.com