Dealing with Big idea 1, which states the process of evolution drives the diversity and unity of life, consider pages 68-69 in chapter 3 of Survival of the Sickest.
In these pages, Moalem addresses the effects of a gene called CYP2D6. First, explain what this gene does. Then, address the consequences of having very few of these genes. Also, address the consequences of having too many copies of this gene. How can this gene lead way to make "personalized medicine?" Which races tend to have higher metabolisms due to excessive CYP2D6 genes? What are some advantages of being a fast metabolizer rather than a slow metabolizer? And lastly, what are some advantages to being a slow metabolizer rather than a fast metabolizer?
(Posted by Lindsay Pontello, lpontel4@students.d125.org)
The CYP2D6 gene and its function relates to Big Idea 4: Biological systems interact, and these systems and their interactions possess complex properties. The CYP2D6 gene is involved in metabolizing over 25% of prescription drugs, including common dugs (pg. 68). To do this, the CYP2D6 gene codes for an enzyme that is a member of the cytochrome P450 superfamily. This family of enzymes catalyzes many reactions that involve metabolizing drugs as well as reactions to synthesize different lipids. The specific protein that the CYP2D6 gene codes for helps metabolize multiple different types of drugs, including some anti-depressants. (http://ghr.nlm.nih.gov/gene/CYP2D6).
ReplyDeleteIf a person has few copies of the CYP2D6 gene are called “slow metabolizers” because the few genes do not produce enough enzymes that function well enough to effectively metabolize a normal dosage of some drugs. These people can experience unpleasant side effects after taking a standard dosage of a drug because their enzymes can’t break that much drug down efficiently; therefore, these types of people should ingest a smaller dosage (pg. 68). If someone has many copies of the gene, they are “fast metabolizers” because their CYP2D6 genes produce large amounts of enzymes for metabolism (pg. 68). Dr. Moalem explains the possibility of “personalized medicine”, meaning that drugs and dosage are altered to fit a person’s genome, and asserts that this approach could have large health benefits (pg. 68). This would work well because doctors, after looking at a person’s genome and focusing on genes involved in drug metabolism, could determine the effectiveness of a drug and/or how much of the drug the person needs to take based on the number of copies of a gene like CYP2D6.
The prevalence of fast or slow metabolizers seems to change in different races. For example, 10% of Caucasians are slow metabolizers but when looking at the Asian races, only about 1% are slow metabolizers. Conversely, fast metabolizers are very prevalent in, as an example, Ethiopians (29%) while less than 1% of Caucasian people are fast metabolizers (pg. 68). Data suggests that quantity of CYP2D6 genes is affected by the “toxicity” of a population’s environment. In populations that resided in areas with more toxins from food or insects, having higher quantities of CYP2D6 genes would be selected for because people with this trait can metabolize and break down (detoxify) harmful substances quicker and more successfully (pg. 69).
Advantages of being a fast metabolizer is just that—any toxins ingested can be metabolized with more speed and a higher rate of success than people who are slow metabolizers. Fast metabolizers also have a much lower chance of experiencing side effects than slow metabolizers because they break down the drug quickly and it does not remain in the liver (http://www.sciencedaily.com/videos/2006/0805-gene_chip_for_personalized_meds.htm). However, fast metabolizers can sometimes convert some drugs into even more potent forms, so in that sense, slow metabolizers have the advantage because they rarely do so (pg. 69). Though slow metabolizers have a higher chance of experiencing side effects, it is also easier for them to take a particular drug and find the drug effective since they need lower doses (http://www.sciencedaily.com/videos/2006/0805-gene_chip_for_personalized_meds.htm). This could be good for medical costs as well because if fast metabolizers take large doses, they frequently have to buy more of the prescription, rapidly increasing the cost.
(Sanika Bhargaw, sbharga4@students.d125.org)
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ReplyDeleteOn pages 68- 70 Dr. Maolem talks about a gene in the human body, CYP2D6 and how it can have a major impact on the body. This relates to Big Idea #2, which states: Biological systems utilize free energy and molecular building blocks to grow, reproduce, and to maintain dynamic homeostasis; CYP2D6 is an important gene affecting how the body metabolizes more than 25% of all pharmaceuticals. People who only have very few copies of this gene are considered ‘slow metabolizers’. It is one of the important enzymes involved in the metabolism of xenobiotics, substances that are foreign to the body. The more copies of this gene, the more quickly your body metabolizes xenobiotics such as pharmaceuticals. Usually fast metabolization is considered to be a positive attribute, but in this case, more copies of CYP2D6 can actually lead to death. Since this gene is directly related to metabolizing drugs, if the body metabolizes the drug too quickly, the drug which was actually harmless and supposed to help you, can easily become much more potent due to the fast conversion. Many people of North African and Middle Eastern descent tend to have higher rates of being an ‘ultrarapid metabolizer’. (http://www.genecards.org/cgi-bin/carddisp.pl?gene=CYP2D6)
While one end of the spectrum can lead to death, CYP2D6 enzyme deficiency can also lead to death. Poor metabolism of the drug could cause the drug to stay in the bloodstream for too long, intoxicating the bloodstream. A study showed that CYP2D6 deficiency could be a factor in ecstasy related deaths. (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1874389/) It is always bad to have any extreme. Both having too many copies or having too less copies have proven to be lethal to the human body. Without the extreme of death, slow metabolizers face other side effects because they’re bodies can not efficiently break down drugs. But, there are couple of advantages and disadvantages for having more copies of the CYP2D6 than less. As Dr. Maolem points out, people who happen to have many copies of the gene can detoxify harmful substances in the environment (68-69). Fast metabolizers tend to have higher rate of success ingesting drugs than people who are slow metabolizers and drugs that are taken are metabolized quicker. Disadvantages, however include that slow metabolizers don’t run the risk of converting harmless drugs into potent forms.
The different rates of metabolism in each person leads to the idea of personalized metabolism. Because, doctors do not prescribe medicine based on metabolism, there is a risk for those who have more copies of the CYP2D6 gene being in danger they otherwise wouldn’t have been in. Dr. Maolem also mentions personalized medicine on page 68, stating that altering dosages of medicine to match a specific person’s genome could have many health benefits. This is very true, and as Sanika stated in the response above, doctors can now study the person’s genome and determine effectiveness of a drug and how it reacts in someone.
Pranathi Merneedi (pmernee4@students.d125.org)