On pg. 74, Dr. Moalem talks about free radicals which relates to Big Idea 3: Living systems store, retrieve, transmit, and respond to information essential to life processes. Free radicals harm the body by causing unwanted chemical reactions and disrupting cellular chemistry that could kill cells prematurely.
Summarize Dr. Moalem's explanation about how free radicals work on a molecular level in general, as well as how they are one of the causes of anemia that occurred in the soldiers that were taking primaquine as an antimalarial drug. Use chemistry terms such as electrons, atoms, molecues etc., and identify specific enzymes, cells and places in the body that were affected by free radicals in the soldiers who took primaquine, as well as side effects and how they occur. Finally, research one specific free radical, identify a specific cellular process and explain how that free radical can interfere with the process. Include terms from the biochemistry, cells, protein synthesis, and other relevant units such as enzymes, competitive/allosteric inhibition, active site, protein structure, etc.
(Posted by Raymon Cao, racao4@students.d125.org)
On page 74, Dr. Moalem describes, in general, a free radical’s mechanism for causing cellular damage. Free radicals, chemically speaking, are molecules that have unpaired electrons. In nature, electrons are meant to occur in pairs; in other words, a single electron looks to pair up with another electron. When molecules have an odd number of total valence electrons, the resulting molecule will have one unpaired electron; this molecule is called a free radical. The free radical, biologically, seeks to find another electron within a cell so that it no longer has any unpaired electrons. In order to do so, the free radical must “pair with electrons in other molecules” (74), causing chemical reactions; however, these chemical reactions can severely disrupt, damage, or even completely destroy a cell’s internal chemistry and lead to major cellular malfunction and the cell’s “early death” (74). As a result, the biological process of aging can be dramatically increased by the presence of a high concentration of free radicals within the body.
ReplyDeleteDuring the Korean War, soldiers were prescribed primaquine, an anti-malarial drug that is now known to be harmful to those individuals with the gene for glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD is an enzyme “thought to be present in every cell in the body” (74), which implies that its role in biological functions is quite important. The enzyme is critical to the function of red blood cells, in which it acts as a biological mop, cleaning away harmful molecules within the red blood cells in order to prevent death of the cells. Notably, these molecules cleaned up by G6PD include free radicals. When a person deficient in G6PD uses primaquine, the primaquine enters red blood cells and causes adverse effects on the cell to make it difficult for malaria (genus Plasmodium) to survive in the red blood cell. This weakens the red blood cell, making it much more susceptible to damage by free radicals. Thus, free radicals can easily destroy primaquine-affected red blood cells, which results in red blood cell deficiency, a condition otherwise known as “hemolytic anemia” (75). By a chain of events resulting from hemolytic anemia, the free radicals directly have a role in the damage of red blood cells, kidneys, heart, and liver. (continued in new comment)
Jeeho Lee (jelee4@students.d125.org)
(continuation of previous comment) One of the most dangerous free radicals found in living organisms is the superoxide molecule (O2-). This free radical is actually utilized by phagocytes of the immune system to kill off invading pathogens. In normal organisms, an enzyme called superoxide dismutase (SOD) neutralizes superoxide anions so that they cannot inflict cellular damage; however, a problem arises when cells lack SOD or when a cell is overwhelmed by its concentration of superoxide. One scholarly article published in March 2013, “A study of free radical chemistry: their role and pathophysiological significance” (URL: http://www.actabp.pl/pdf/1_2013/1.pdf) notes that the superoxide radical works not by inhibiting or interfering with a specific biological process, but interfering with functions of certain molecules (and in turn, many biological processes), including but not limited to “lipids, DNA, RNA, […and] steroids” (3). According to the same article, superoxide interferes with such molecules so easily because of its role as both an oxidizing agent (pulling electrons away from a molecule; this is evidenced by its reaction with cytochrome complex in the mitochondrial electron transport chain, which would interfere with photosynthetic and energy transfer processes in many different organisms, preventing organisms from being able to synthesize ATP, the most important source of potential energy in biology; Unit 6, plants and photosynthesis) and as a reducing agent (donating electrons to other molecules; this is evidenced by its reduction of ascorbate, or vitamin C). Furthermore, superoxides can even react with “NADH bound to the active site [the site at which an enzyme can bind to its specific substrate; Unit 2, biochemistry] of the enzyme lactate dehydrogenase to form an NAD∙ radical” (3) bound to the lactate dehydrogenase enzyme, which would cause competitive inhibition as the NAD∙ radical would completely prevent lactate from binding to the enzyme. Thus, superoxide can harm a cell in many different ways by interfering with the way that certain molecules can function within a cell.
ReplyDeleteJeeho Lee (jelee4@students.d125.org)