Drugs can have many differing affects on people, whether their consumption leads to a positive or adverse response. All of this depends on the levels of enzymes in the body and how the variations of expression lead to these possible outcomes. The major theme of the two sources on this topic relate to the specific enzyme, CYP3A. CYP3A is a subfamily of cytochrome P450 enzymes, which serve to catalyze the addition of oxygen into molecules. Their ultimate role serves two spectrums: to convert foreign substances into less toxic products that can be eliminated from the body, or to convert nontoxic substances into toxic forms (Eichelbaum & Burk, 2001). This function is the reason behind the level of expression determining either a positive or adverse drug response. The two sources introduce the genetic variability of enzyme expression, in which pharmacogenomics, the study of how genes affect drug response, is studied with people’s metabolism to test drug concentrations.
The article from Nature Medicine examines, specifically, the CYP3A4 isoform, which is most abundant in the liver and the gut (Eichelbaum & Burk, 2001). The expression of this isoform mainly implies that the same dosage of a drug can vary in the way people respond to its administration, in which some people experience toxic side effects. The source states, “60-90% of person-to-person variability in CYP3A function is caused by genetic factors” (Eichelbaum & Burk, 2001). These genetic factors are then further described as being caused from polymorphisms of the enzyme coding regions, which cause the variability of expression. Looking at CYP3A4 specifically, scientists found that the enzyme expression could be regulated at the transcriptional level using either these polymorphisms or the genes encoding the transcription factors (Eichelbaum & Baum, 2001). This variability essentially serves as the reason behind person-to-person variations in positive or adverse drug responses and the appearance of side effects. They hope that understanding these differences will allow them to determine an effective dosage of drug administration for each individual.
The enzyme, CYP2D6, another subfamily of the cytochrome P450 enzymes found in the liver, and its role in metabolism is the main point of study in the source from The Clinical Biochemist Reviews (Shenfield, 2004). The genetic variability in the role of metabolism creates three groups of individuals: extensive metabolizers (EM), poor metabolizers (PM) and ultra-rapid metabolizers (URM). The variability in the way individuals metabolize drugs causes these differences in drug responses and the appearance of side effects. Examining the expression of CYP2D6, “PMs have higher than normal plasma drug concentrations and hence an increased incidence of adverse drug reactions” (Shenfield, 2004). On the opposite spectrum, extensive metabolizers are found to have a variable range of plasma drug concentrations, which allow them to regulate induction or inhibition caused by certain drugs (Shenfield, 2004). Pharmacogenomics then uses these findings to test which drugs are metabolized by the enzyme, CYP2D6, in order to determine an appropriate and effective dosage for drug administration.
Overall, the biggest connection between the two sources is the genetic variability in enzyme expression and its furthering role in metabolism. The expression of the CYP3A subfamily of the P450 enzymes, the most abundant in the human body, is caused by the differing genes or in the coding regions themselves. These variations then affect the type of metabolism that is introduced in an individual, depending on their genetic traits, and how this affects their response to certain drugs. Ultimately, the goal in both sources is to test these findings and determine an effective dosage of drug administration that serves these genetic variations, while monitoring side effects. This goal can happen more successfully looking at the connections between the two sources and their correlating tests, allowing them to have more information to determine dosage.
The first law of thermodynamics can explain the course theme of biochemical processes following thermodynamic laws, looking at metabolism, which converts this drug consumption into energy. The first law of thermodynamics states that energy can neither be created nor destroyed, and metabolism is an example of this law in the sense that energy remains in the system even when converted and released as heat. Extensive metabolizers release more heat and do not suffer from as many side effects because the drug is not stored as much in the body. On the other hand, slow metabolizers do not burn as much energy and the drug remains stored in the body more easily, explaining why they experience adverse drug responses and the appearance of side effects. Using the connection between these biochemical processes and this thermodynamic law will help assist determining how an appropriate dosage can be administered.
While each source looks deeper at either the variation in enzyme expression or the variation in metabolism types, genetic variability serves to be the sole cause of drug responses. The connection between these sources and their correlating experiments allow them to determine dosage of drug administration and the way it will affect individuals.
I have learnt that biochemistry is not just concerned with the drug interactions but also the influence of genetics on the effects of the drug response.
Even though your topic sentence comprises of concepts from both articles, you still did not introduce the two articles in the introductory paragraphs. You compensate this very well in the body of your paper because you use the two articles effectively to support your arguments. You transition between sentences and paragraphs makes the paper readable. However, the readability can be improved by using shorter sentences. Your paper could also benefit from the use of in-text citations. More citations are needed towards the end of the paper.
Works Cited
Burk, O., & Eichelbaum, M. (2001, March). CYP3A Genetics in Drug Metabolism. Nature Medicine, 7(3), 285-287. doi:10.1038/85417
Shenfield, G. M. (2004). Genetic Polymorphisms, Drug Metabolism and Drug Concentrations. The Clinical Biochemist Reviews, 25(4), 203–206. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1934960/
