Metabolomics/Analytical Methods/Mass Spectrometry/Tandem-MS
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Tandem mass spectrometry, also known as MS/MS, involves multiple steps of mass spectrometry selection, with some form of fragmentation occurring in between the stages. Fragmentation of gas-phase ions is very important in MS/MS, and it takes place between various stages of mass analysis. (http://en.wikipedia.org/wiki/Tandem_mass_spectrometry) Different fragmentation methods are: In-source fragmentation and Post-source fragmentation. Tandem mass spectrometry is used to identify chemicals, that are very hard or impossible to identify by any other methods due to their low concentrations, polarity, or lack of chromophore. It is a powerful tool in identification of inherited metabolic disorders, when an accurate and timely diagnostics of which can be essential to the wellbeing of the patient.
Article 1:
Clinical applications of tandem mass spectrometry: ten years of diagnosis and screening for inherited metabolic diseases. edit
(By: Mohamed S. Rashed)
General Overview:
The main focus of this article is to provide a detailed explanation of the two main Tandem Mass Spectrometry (MS-MS) screening methods, such as MS–MS-based newborn screening, and MS–MS-based selective. The review contains information about the evolution and development of MS-MS from fast atom bombardment MS-MS to electrospray ionization MS-MS. The author shows the unique advantages of MS-MS for use in genetic laboratories and at the newborn screening programs around the world. Also the review points out benefits of the tandem mass spectrometry over the other analytical methods available.
New Terms:
Beta-ketothiolase deficiency – a rare, autosomal recessive metabolic disorder in which the body cannot properly process the amino acid isoleucine or the products of lipid breakdown. http://en.wikipedia.org/wiki/Beta-ketothiolase_deficiency
Maple syrup urine disease (MSUD) – also called branched-chain ketoaciduria, is an autosomal recessive metabolic disorder affecting branched-chain amino acids. It is one type of organic acidemia. http://en.wikipedia.org/wiki/Maple_syrup_urine_disease
Sudden infant death syndrome (SIDS) – is a syndrome marked by the symptoms of sudden and unexplained death of an apparently healthy infant aged one month to one year. http://en.wikipedia.org/wiki/Sudden_infant_death_syndrome
Mitochondrial trifunctional protein deficiency – is an autosomal recessive fatty acid oxidation disorder that prevents the body from converting certain fats to energy, particularly during periods without food . People with this disorder have inadequate levels of an enzyme that breaks down a certain group of fats called long-chain fatty acids. http://en.wikipedia.org/wiki/Mitochondrial_trifunctional_protein_deficiency
Propionic academia – also known as propionic aciduria, or sometimes referred to as ketotic glycinemia, is an autosomal recessive amino acid disorder, classified as a branched-chain organic acidemia, which presents in the early neonatal period with progressive encephalopathy. http://en.wikipedia.org/wiki/Propionic_acidemia
Metabolomics Relevance:
The article points out new methods for identification of metabolic disorders, which are caused by mitochondrial enzyme defects, and mitochondrial fatty acid oxidation defects, in which acetyl-CoA accumulates in mitochondria. L-carnitine helps remove acetyl-CoA through formation of acylcarnitine esters, restoring mitochondrial homeostasis. Acylcarnitine can be considered a unique chemical fingerprint, which metabolomics is a study of.
Article 2:
Screening blood spots for inborn errors of metabolism by electrospray tandem mass spectrometry with a microplate batch process and a computer algorithm for automated flagging of abnormal profiles. edit
(by: Mohamed S. Rashed et al.)
URL: http://www.clinchem.org/cgi/content/abstract/43/7/1129
General Overview:
This article focuses on ESI-MS/MS (electrospray tandem mass spectrometry) and how it is paving the way for new opportunities. The introduction of ESI-MS/MS as a diagnostic tool in our metabolic unit has had a great impact on the number of cases diagnosed as organic acidemias or aminoacidopathies from sick children. It focuses on the research that is being done in order to find biomarkers in metabolomics in order to better understand the human body.
New Terms:
Neonatal screening - Newborn screening is the process of testing newborn babies for treatable genetic, endocrinologic, metabolic and hematologic diseases. http://en.wikipedia.org/wiki/Neonatal_screening
Hypermethioninemia - an excess of the amino acid methionine, in the blood. This condition can occur when methionine is not broken down properly in the body. http://en.wikipedia.org/wiki/Hypermethioninemia
Homocystinuria - also known as Cystathionine beta synthase deficiency, is an inherited disorder of the metabolism of the amino acid methionine, often involving cystathionine beta synthase. It is an inherited autosomal recessive trait, which means a child needs to inherit the defective gene from both parents to be affected. http://en.wikipedia.org/wiki/Homocystinuria
Galactosemia - is a rare genetic metabolic disorder which affects an individual's ability to properly metabolize the sugar galactose. http://en.wikipedia.org/wiki/Galactosemia
Acylcarnitines - are fatty acids or organic acids that are bound to carnitine. http://www.idph.state.il.us/HealthWellness/msmsfaq.htm
Metabolomics Relevance:
MS/MS detects abnormal levels of amino acids and acylcarnitines. Abnormal elevations of these amino acids may indicate the newborn is at risk for disorders of amino acid metabolism. This is relevant to what we have learned so far in the course in that we have talked about free carnitine as a chemical that acts as a transporter of fatty acids into and out of the mitochondria, and is necessary for normal energy metabolism. Acylcarnitines are fatty acids or organic acids that are bound to carnitine. These acylcarnitines vary in size, based on the number of carbon atoms and the type of chemical bonds within the molecule. Abnormal levels of these acylcarnitines can act as markers for certain organic acid and fatty acid oxidation metabolic disorders.
Articles and Web Pages for Review and Inclusion edit
Peer-Reviewed Article #1:
Towards de novo identification of metabolites by analyzing tandem mass spectra
Bioinformatics 2008 24(16):i49-i55'"
Main Focus edit
- Identify the main focus of the resource. Possible answers include specific organisms, database design, intergration of information, but there are many more possibilities as well.
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Summary edit
- Enter your article summary here. Please note that the punctuation is critical at the start (and sometimes at the end) of each entry. It should be 300-500 words. What are the main points of the article? What questions were they trying to answer? Did they find a clear answer? If so, what was it? If not, what did they find or what ideas are in tension in their findings?
Relevance to a Traditional Metabolism Course edit
- Enter a 100-150 word description of how the material in this article connects to a traditional metabolism course. Does the article relate to particular pathways (e.g., glycolysis, the citric acid cycle, steroid synthesis, etc.) or to regulatory mechanisms, energetics, location, integration of pathways? Does it talk about new analytical approaches or ideas? Does the article show connections to the human genome project (or other genome projects)?