Contribution of Mitochondria to the Cellular Energy Budget and the Ethical Implications of Mitochondrial DNA - Essay Example

Contribution of mitochondria to the cellular energy budget and the ethical implications of mitochondrial DNA analysis Introduction Introduction Cells carry out numerous functions that are energy dependent. Therefore, energy is vital for cell survival and maintenance of a stable, cellular environment. Apart from this primary role of cellular energy, cells require energy for growth, development, and reproduction. The cell membranes allow substances to pass in and out of the cell, a process which also relies on energy. For these processes to occur there, must be sufficient sources of energy that supply cells with the required energy. The main sources of energy are organic fuel molecules, which are oxidized by cells through a process referred to as respiration (Karp 2009, p.111). Discussion The best sources of cellular energy are those rich in hydrocarbons due to the presence of hydrogen electrons, which are readily oxidized. The oxidized electrons provide the required energy. There are numerous organic compounds that can be oxidized, but glucose serves as the main fuel molecule for cells, hence the term glucose metabolism or glucose oxidation. The two terms are used interchangeably to refer to pathways involved in cellular respiration. Glucose is derived from photosynthesis. Examples of organic foods that are rich sources of energy include sugars, fats, and proteins. This is because energy used in the synthesis of these food products is stored in chemical bonds holding the molecules (Karp 2009, p119). Cells release this energy through oxidation reactions. The term oxidation refers to a series of chemical reactions whereby electrons are transferred from one molecule to another. This transfer changes the energy content and its composition in acceptor and donor molecules. During these transfers, food molecules serve as the electron donor. In each oxidation process, products obtained are of lower energy content compared to the donor molecule involved in the initial steps of the pathway. On the other hand, electron acceptors get hold of the energy lost during oxidation reactions and keep it for future use (Starr & McMillan 2011, p.41). It is necessary to note that cells do not utilize oxidation energy immediately, but rather convert it into energy rich molecules. These molecules include ATP (adenosine tri-phosphate) and NADH (nicotinamide adenine dinucleotide). These molecules are responsible for providing the energy needed by the cell for various functions. ATP is the most crucial energy molecule in cellular respiration. It is made of an adenosine base, ribose sugar, and a phosphate chain. The key to ATP’s high energy storage capacity is the high-energy phosphate bond within the phosphate chain (Starr & McMillan 2011, p.57). The energy pathway to be applied by a cell depends on the type of cell. In eukaryotic cells, there are three main processes employed in the transformation of energy present in chemical bonds into usable forms of energy. The first of these processes is glycolysis, which refers to the process of sugar breakdown. During this process, a molecule of glucose is catabolized produce two pyruvates. Glycolysis is a ten step process, which is dependent of two ATP molecules at the initial steps. The two ATP molecules then yield four new ATP molecules, which imply that there is a net gain of two ATPs in glycolysis. In addition, two molecules of NADH are also produced (Harvey & Ferrier 2011, p.85). The second step of the energy pathway relies on the pyruvates generated during glycolysis. During this process, the pyruvate molecules present in the cytoplasm move into the mitochondrion. Within this cellular organelle, they are converted into acetyl CoA, which is a two carbon energy carrier. The third carbon that forms the acetyl CoA combines with oxygen to form carbon dioxide plus a molecule of NADH. The acetyl CoA forms a vital component of the citric acid cycle, which is the other key process, used to generate cellular energy. The citric cycle occurs in eight steps, to produce three extra NADH molecules and FADH2 and GTP, which are the other carrier molecules (Harvey & Ferrier 2011, p.87). The final energy process is the electron transport chain. The process is involved in the transfer of electrons from NADH and FADH2 through mitochondrial membranes where they later combine with oxygen to form water (Karp 2009, p187). The mitochondrion is the cellular organelle where that cellular respiration takes place. This organelle occurs in the cytoplasm of eukaryotic cells. The mitochondrion has two membranes, which form distinct compartments in mitochondrion. The outer membrane is made of phospholipid bilayer, which has protein structures referred to as porins. These protein structures create the channels through which substances such as ATP, ions, and nutrients pass. The inner membrane allows the free movement of oxygen, carbon dioxide, and water (Starr & McMillan 2011, p.60). Its structure is complex and holds components of the ETC, ATP synthetase and transport proteins. The inner membrane is highly folded to form cristae. This folding increases the organelle’s surface for oxidative phosphorylation. The mitochondrion has a matrix, which contains the essential enzymes for citric acid cycle processes. In addition, the matrix also has dissolved oxygen, water, carbon dioxide, and energy shuttles (Starr & McMillan 2011, p62). Discovery of the mitochondrion occurred in late 19th century. Its name was coined from Mito, which means thread and khondrion, which means granule. This was inspired by the thread forming granules observed under the light microscope. The origin of the mitochondrion is supported by the hypothesis, which postulates that the mitochondrion came from primitive aerobic, non-photosynthetic bacteria. This group of bacteria found its way into the eukaryotic cell and managed to establish a symbiotic relationship with the cell. The hypothesis further states that the mitochondria enabled the cell to obtain energy, and in return, the cell synthesized vital components of the mitochondria (Karp 2009, p113). It is believed that the outer membrane part of the mitochondria is the remnant derived from the cell’s endocytic vesicle while the inner membrane is the bacterial membrane. The two membranes vary significantly in their chemical composition (Karp 2009, p.114). Overview of pyruvate oxidation Two molecules of pyruvate are formed in the cytosol after the glycolytic pathway. Each molecule of pyruvate is then moved into the mitochondria for catabolic reactions to form water and carbon dioxide. The transfer of the pyruvate molecules utilizes two ATP molecules. The citric acid cycle is involved in the final breakdown of the pyruvate molecules. However, before the start of the citric acid cycle, the pyruvates are fragmented to produce a two carbon fragment referred to as acetyl. This occurs as a result of loss of two hydrogen atoms and a molecule of carbon dioxide. Transfer of acetyl into the citric acid cycle is facilitated by coenzyme A (CoA). After delivering the acetyl, the CoA returns to pick other acetyl fragments (Starr & McMillan 2011, p70). Overview of the citric acid cycle This is a regenerating cycle that is made of 4-, 5-, and 6-carbons that are of organic acids. Before getting into the citric acid cycle, the part of the pyruvate is removed to from a 2-carbon fragment. Within the cycle, the 2-carbon fragment combines with oxaloacetic acid, which is a 4-carbon molecule. The resulting molecule is the 6-carbon molecule referred as citric acid. During the subsequent processes of the cycle, carbon dioxide is released from the citric acid to form a 5-carbon acid. The latter then loses another carbon dioxide to form a 4-carbon organic acid. The formation of the 4-carbon acid marks the beginning of a new cycle since the initial oxaloacetic acid molecule is regenerated (Karp 2009, p180). Overview of the electron transport chain (ETC) This is also referred to as oxidative phosphorylation. This process involves the transfer of electrons originating from the citric cycle to a chain of electron acceptors. These electron acceptors include NAD, FAD, coenzyme Q, cytochrome A3, cytochrome A, cytochrome B, and cytochrome C. During this chain of reactions, energy is moved from ETC during the coupling of Pi to ADP, which results to the formation of ATP. The addition of Pi (inorganic phosphate) is referred to as phosphorylation. In situations where a pair of electron s is moved across the entire process of ETC, ATP is generated in 3 different places (Karp 2009, p187). The essence of the ETC is to synthesize ATP and shuttle protons (H) and electrons to oxygen in order to produce water. NADH2 and FADH2 are two key electron carriers. NAD is a coenzyme which is derived from vitamin B3. NADH has the potential to form NAD+ through the loss of hydrogen and an electron. Phosphorylation of NADH forms NADPH, which is an essential molecule in energy pathways. FAD (flavin-adenine dinucleotide), is the other essential electron carrier. This molecule is derived from vitamin B2. Reduction of FAD leads to the formation of FADH2, which acts as an essential electron carrier (Karp 2009, p190). Mitochondria DNA (mt DNA) Mitochondria holds small amounts of DNE referred to as mitochondria DNA (mtDNA). In humans, the size of mtDNA is about 16, 500 base pairs, which represents a small fraction of the total DNA present in cells. Mitochondrial DNA has 37 genes, which are essential for optimal functioning of the mitochondrial. Thirteen genes are responsible for issuing instructions for the synthesis of enzymes responsible for oxidative phosphorylation. The remaining genes provide instructions for the synthesis of transfer RNA (tRNA) and ribosomal RNA (rRNA) (Lemasters & Nieminen 2001, p7). Disorders ARISING from faults in mtDNA Defects on the mtDNA are associated with several genetic disorders. These changes may occur as a result of gene deletion, mutation, replacement or any other factor that may lead to changes on the gene sequence. Medical disorders that may arise from gene defects include cyclic vomiting syndrome, cytochrome C oxidase deficiency, kearns-Sayre syndrome, leber hereditary optic neuropathy, leigh syndrome, maternally inherited diabetes and deafness, and myoclonic epilepsy with ragged-red fibers. Other medical disorders include neuropathy, ataxia, and retinitis pigmentosa, nonsyndromic deafness, and some forms of cancer (Lemasters & Nieminen 2001, p240). Analysis of mtDNA Analysis of mtDNA is usually done through a process of DNA sequencing. This process helps in analyzing and comparing DNA samples located in the mitochondria. Application of mtDNA sequencing is mostly forensic science and other scenarios where identification of the genetic material is necessary. Inheritance of mtDNA is almost exclusive from the mother, and it is estimated that less than 0.01% of mtDNA is inherited from the father. With such facts, scientists can study maternal lineages over several generations (Butler 2005, p255). The process of mtDNA sequencing occurs in five steps. This steps start with sample preparation, mtDNA extraction, PCR amplification, mtDNA purification and quantification, and final step, which involves sequencing. The use of PCR technique helps the amplification of hypervariable sections of mtDNA. Samples that can be used to extract mtDNA include teeth, bones, and hair (Butler 2005, p257). Ethical issues surrounding mtDNA sequencing Some of the applications of the mtDNA sequencing are faced with a number of ethical concerns. The use of mtDNA sequencing, in the identification of gene defects in embryos, is surrounded by a number of ethical issues. The main issue of concern is on the potential risks associated with the replacement of default mtDNA. Therefore, correction of damaged embryonic mtDNA using a damaged mtDNA may cause a serious medical condition to the developing embryo (Butler 2005, p.263). The other ethical surrounds the use of mtDNA in the study of generations. Scientists apply knowledge of mtDNA to follow genetic matrilineage, which helps is analyzing peoples’ migration patterns. Opponents of this exercise argue that documentation of findings obtained from the study may create hostility between native communities and immigrants (Butler 2005, p265). Conclusion As mentioned, production of cellular energy occurs in three pathways. In glycolysis, a total of 4ATPs and 2NADH are produced, but this pathway utilizes 2ATPs to form a net of 2ATPs and 2NADH. The citric acid cycle produces 2ATPs, 8NADHs, and 2FADHs from every molecule of glucose. The final pathway (the electron transport chain) produces 32ATPs obtained from NADH and FADH generated in glycolysis and citric acid cycle. Application of mtDNA sequencing ranges from identification of persons, solving crimes, diagnosis of genetic defects to selection of embryos for IVF. In the recent past, there have been numerous arguments regarding the use mtDNA sequencing in the treatment of gene defects in embryos. References List Butler, J. M. (2005). Forensic DNA Typing: Biology, Technology, and Genetics of Str Markers, Chicago, Academic Press. pp.253-270. Harvey, D. & Ferrier, R. (2011). Biochemistry: Biochemistry, North American Edition, New York, Lippincott Williams & Wilkins. pp.78-93. Karp, G. (2009). Cell and Molecular Biology: Concepts and Experiments, New York, John Wiley & Sons. pp. 105-195. Lemasters, A.& Nieminen, L. N. (2001). Mitochondria in Pathogenesis, London, Springer. pp.7-240. Starr, B. & McMillan,C. (2011). Human Biology, New York, Cengage Learning. pp. 41-90 Read More