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The Magnesium Project - Metabolomics
Definition Metabolomics is the study of metabolism and the various biochemical pathways, components and regulatory systems associated with it. Metabolomics also includes the processes involved in breakdown of compounds (catabolism) as well as the formation of new compounds (anabolism). Diseases of Metabolism Diseases of metabolism cover a lot of area. Diseases are characterized by one or more defects in the genetic code or the translation thereof in going from reading of a segment of the DNA code to formation of mRNA and subsequent forms of RNA that direct protein synthesis. Diseases are often the result of an accumulation of one or more mutations, copy number variations (CNV) or single nucleotide polymorphisms (SNP). There are more than 1600 metabolic pathways each of which may be comprised of dozens of enzyme-catalyzed reactions. Thus, there are many opportunities for mistakes to happen. Mistakes in fact do happen but there are also systems in place to discard the "mistakes." The mechanisms to detect and discard mis-formed proteins may also be defective and become a contributor to a particular disease. Diabetes Melitus (Type II) Diabetes is a disease related to the metabolism of sugar/carbohydrates. Distinguished from Type I (Juvenile diabetes) which is an auto-immune disease in which the body immune system cells attack the pancreatic cells, Type II is a metabolic disease. It is comprised of several system components including the hormones glucagon and insulin and structural elements including the Islets of Langerhan in the pancreas and Eccrine cells. Menni and colleagues (1) have taken a metabolomics approaches and identified 447 fasting plasma metabolites. Forty-two metabolites from three major fuel sources, carbohydrates, lipids and proteins, were found to significantly correlate with Type II diabetes (T2D) after adjusting for multiple testing; of these, 22 were previously reported as associated with T2D or insulin resistance.> Fourteen metabolites were found to be associated with Impaired Fasting Glucose (IFG). They concluded that results confirm an important role for catabolism of branched-chain-amino-acids in T2D and IFG. Metabolomics in Pregnancy In another example of the application of a metabolomics approach, Fanos and colleagues (2) have applied metabolomics in maternal-fetal medicine. Tissues used for metabolomics interrogations of pregnant women, fetuses and newborns include amniotic fluid, blood, plasma, cord blood, placenta, urine, et al. Papers reviewed highlight the strong correlation between biomarkers found in these tissues and fetal malformations, preterm delivery, premature rupture of membranes, gestational diabetes mellitus, preeclampsia, neonatal asphyxia, and hypoxic-ischemic encephalopathy. They emphasize the clinical potential of metabolomics in obstetrics in the immediate future. Metabolomics represents a holistic approach to the metabolites that constitute a cell, tissue, or organism (3). It is able to provide a phenotypic fingerprinting of a cell, tissue, or organism by virtue of its ability to measure multiple metabolites directly from complex biological systems. Fanos (3) further explains that the metabolomic approach consists of two sequential phases. The analytical phase is designed to profile all low molecular weight metabolites in a given biological specimen to generate an all-inclusive spectrum. Possible sources of biological tissues that can be exploited in pregnancy are both from the mother, the fetus, and the newborn. Different technologies might be generally adopted: nuclear magnetic resonance (NMR) spectroscopy, gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS). The data analysis and interpretation phase requires highly complex data mining software and an ample database of metabolites to describe the nodes and networking of metabolic pathways. These phases are described in detail in studies performed in pregnant women and neonates (4). Diaz and colleagues (5) extend the technique to include the determination of chromosomal defects (trisomy 21). They write that specific urinary metabolic signatures were unveiled for central nervous system malformations, trisomy 21, preterm delivery, gestational diabetes, intrauterine growth restriction and preeclampsia. They used (1)H Nuclear Magnetic Resonance and a number of statistical tools. References 1. Menni C, et al. Biomarkers for type 2 diabetes and impaired fasting glucose using a non-targeted metabolomics approach. Diabetes. 2013 Jul 24. PMID: 23884885 2. Fanos V, Atzori L, Makarenko K, Melis GB, Ferrazzi E. Metabolomics application in maternal-fetal medicine. Biomed Res Int. 2013;2013:720514. doi: 10.1155/2013/720514. Epub 2013 Jun 9. PMID: 23841090 3. R. P. Horgan, O. H. Clancy, J. E. Myers, and P. N. Baker, “An overview of proteomic and metabolomic technologies and their application to pregnancy research,” BJOG, vol. 116, no. 2, pp. 173–181, 2009. ( http://dx.doi.org/10.1111/j.1471-0528.2008.01997.x) 4. V. Fanos, M. Mussap, A. Noto, and L. Atzori, “Metabolomics in perinatology: where are we now?” Acta Medica Portuguesa, supplement 2, pp. 117–120, 2012. 5. Diaz SO, et al. Second trimester maternal urine for the diagnosis of trisomy 21 and prediction of poor pregnancy outcomes. J Proteome Res. 2013 Jun 7;12(6):2946-57. doi: 10.1021/pr4002355. Epub 2013 May 9. PMID: 23611123 ----------------------------------------
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