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CYP450 Enzymes and Ethnic Variations The Vitamin D Issue In my last article in NEXUS [19/02], I discussed the Vitamin D is metabolised by CYP24 and CYP27, but role of the common class of drugs called "beta- other CYPs may be involved as they metabolise blockers", prescribed originally for hypertension but cholesterol. The issue of vitamin D is very complicated. now given for anxiety, post-traumatic stress disorder | Many people are being found to have low blood levels and cancer. of vitamin D, and many practitioners are dealing with The role of beta-blockers—first noted in 1989 in _ this simplistically. Some people found that when they causing "permanent anaphylactic reactivity", presumably took vitamin D supplements—often prescribed in what is now called "mast cell disease’—was cited. It is | massive doses—they became ill. They may have hidden CYP2D6 that processes beta-blockers. It is also known porphyria or other problems with CYP450 enzymes. that many people lack a functioning 2D6, and this varies One protocol now being used involves people with according to race/ethnicity. chronic fatigue syndrome or any inflammatory or L. DiAnne Bradford found: "Over 40 cytochrome P450 environmental illness rigorously avoiding supplements (CYP) 2D6 allelic variants have been discovered thus far. and foods with any appreciable vitamin D content. The alleles may be classified on the basis of the level of Supposedly this needs to be done for years before activity for which they encode CYP2D6 enzymes, into improvement is felt. | think that, rather, the matters functional, non-functional and reduced function groups. discussed herein and in my previous articles need to be CYP2D6 allele frequency is known to vary amongst addressed. However, it may be correct for some people racial/ethnic groups. to avoid vitamin D ingestion—especially in massive “Generally, for European doses—even if they have low Caucasians and their blood levels. This should be descendants, the functional dealt with individually. group of alleles are Perhaps it is the body's predominant, with a frequency It must be noted that wisdom to have caused the of 71%. Non-functional alleles HS low level. represent 26% of the variability, because of CYP deficiency It must be noted that mainly CYP2D6*4. In Asians or defect, there may be because of CYP deficiency or and their close descendants, defect, there may be people unctional alleles represent people who cannot safely who cannot safely take any only ~50% of the frequency of take any supplements. supplements. Such people CYP2D6 alleles. Asians and should learn energy balancing Pacific Islanders have a high requency (median = 41%) of a reduced function allele, to improve their health. Getting tested for as many CYP450 enzymes as possible is CYP2D6*10...indicating slower metabolism..."* a good idea, especially if you have any chronic illness, The article goes on to cite differences in 2D6 for other or indeed just for longevity. The ability to do this varies ethnic groups. by country. In the USA, until June 2009 it was easy to get such testing. Several companies had offered panels Multidrug Resistance Protein which tested for numerous CYP450s. They were Another class of compounds has been found to assist variously labelled as “immunological panel", he CYP enzymes. There is an association between "cardiovascular panel", etc. Then the FDA banned these some CYPs and the transmembrane pump protein, P- _ tests. If your country also is making this difficult, I've glycoprotein | (Pgp1) (the "P" stands for "permeability"). | thought of one way around this... t's also being called "multidrug resistance protein 1". It The drug companies are making it easy, and soon ransports a wide variety of substrates across extra-~ and perhaps mandatory, to get tested for various intracellular membranes, and is found in the liver, cytochrome P450 enzymes that detoxify the drugs they pancreas, kidney, colon, jejunum, adrenal gland and manufacture. Yet some of these CYPs are the very same capillary endothelial cells comprising the blood-brain and —_ ones involved in various chronic illnesses. While the blood—testis barriers. drug companies are interested in selling more drugs It binds to adenosine triphosphate (ATP) as well as to —_ and not being sued, you can make use of what they are he substrate. Pgpl functions as a transporter in the _ facilitating for the ends I have described here! blood-brain barrier and is involved in drug resistance. Likewise, if you suspect you have porphyria—and t transports lipids, steroids, xenobiotics/drugs, _ recall that I have written that the tests for this are easily peptides and bilirubin across cell membranes. It aids interfered with or perhaps deliberately corrupted—then CYP4503A in the task of removing toxic metabolites and once again try to get CYP450 testing. Because these xenobiotics from cells into urine, bile and the intestinal tests are not readily interfered with is perhaps the umen. reason why they were banned in the USA. or defect, there may be , people who cannot safely take any supplements. Multidrug Resistance Protein Another class of compounds has been found to assist the CYP enzymes. There is an association between some CYPs and the transmembrane pump protein, P- glycoprotein | (Pgp1) (the "P" stands for "permeability"). It's also being called "multidrug resistance protein 1". It transports a wide variety of substrates across extra- and intracellular membranes, and is found in the liver, pancreas, kidney, colon, jejunum, adrenal gland and capillary endothelial cells comprising the blood-brain and blood—testis barriers. It binds to adenosine triphosphate (ATP) as well as to the substrate. Pgpl functions as a transporter in the blood-brain barrier and is involved in drug resistance. It transports lipids, steroids, xenobiotics/drugs, peptides and bilirubin across cell membranes. It aids CYP4503A in the task of removing toxic metabolites and xenobiotics from cells into urine, bile and the intestinal lumen. JUNE - JULY 2012 NEXUS ° 41 It must be noted that because of CYP deficiency www.nexusmagazine.com