Lecture 8 in Powerpoint format

Fucose l alanine l asparagine l aspartic acid l

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Unformatted text preview: eucine L-Lactic Acid L-Lysine L-Methionine L-phenylalanine L-Serine L-Threonine L-Valine Malonic Acid Methylamine Mono-methylmalonate N,N-dimethylglycine N-Butyric Acid Pimelic Acid Propionic Acid Pyruvic Acid Salicylic acid Sarcosine Succinic Acid Sucrose Taurine trans-4-hydroxy-L-Proline Trimethylamine Trimethylamine-N-Oxide Urea High Throughput Technologies: High Transcriptomics, Proteomics and Metabolomics Diverse applications (e.g. biomedical, toxicology, environmental) Generic features Transcriptomics Arrays Scanning Proteomics Gels MS Columns Arrays & Scanning Metabol/nomics MS FTIR … NMR … Some technologies in common Methods LC-MS: Liquid chromatography, commonly high performance LC(HPLC) on any kind of stationary phase (e.g. reversed phase, normal phase or ion exchange), coupled with mass spectrometry. Analytes are separated by their chemical properties (e.g.hydrophobicity, hydrophilicity or charge). GC-MS: Gas chromatography, commonly applied to coated capillary columns, coupled to MS. Analytes separated by their boiling points & their interaction with the liquid layer covering the capillary in the gas phase. CE-MS: Capillary electrophoresis coupled to MS. Electrically charged analytes separated by their mobility in a capillary filled with an electrolyte under the influence of an electric field. **New advances in mass analyzers in mass spectrometers are allowing much more sensitive and accurate determinations of metabolites Applications: Applications: Metabolomics is beginning to be used in: • clinical chemistry clinical • pharmacology • toxicology toxicology • pre-clinical drug trials • transplant monitoring • newborn screening newborn • Physicians and scientists are realizing that metabolic profiling could have a significant impact on the diagnosis, prediction, prevention and monitoring of many genetic, infectious and environmental diseases. Current challenges Current No single technique is suitable No for the analysis of the different types and sizes of molecules types E.g., hydrophobic lipids vs hydrophilic peptides hydrophilic To ‘capture’ the whole To metabolome a variety of techniques must be used. techniques We don’’t even know how many t metabolites to expect – still at the “tip of the iceberg” ! the Summary I Basic principles of thermodynamics govern the transfer of energy in biological systems A thermodynamic system can be a single simple chemical reaction, or an entire organism If delta G is negative, reactions can proceed spontaneously; if it is positive, then energy must be invested; if it is zero, then the reaction is at equilibrium. The standard free energy change is a physical constant and can be calculated from the equilibrium constant Summary II The actual free energy change depends on the concentrations of products and reactants, temp. and pH. Standard free energy changes are additive. Individual reactions with unfavourable (positive) values can proceed if coupled to those with favourable (negative) values. High energy compounds – high group transfer potential molecules – are used to drive energetically unfavourable reactions. Summary III Summary Metabolomics Metabolomics is is rapidly becoming a leading-edge analytical approach. approach. is a comprehensive approach which allows high sample throughput complements results genomics and proteomics. are beginning to be integrated into a broader picture, to improve the understanding of biochemical networks (Systems Biology)....
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