Metabolic profiling, the elucidation of the small molecule components of a cell, tissue or organism, has emerged as a useful technique in such diverse fields as drug discovery, clinical diagnostics and plant biochemistry. With the recognition that there is additional information in systems integration, the terms Genomics and Proteomics have been coined to describe the information contained in the complement of genes and proteins. In a like manner, the information gleaned from endogenous metabolic profiling has been described as the Metabolome. Many additional terms have entered the lexicon describing specific uses of such data, such as Molecular Proteomics™ and Metabonomics. Despite confusion about the exact meaning of such terms, it is clear that there is valuable information contained in metabolic profiling or Metabolomics.
The small molecule inventory (SMI) or Metabolome is a pattern of molecules that reflects the cell’s status. It is the totality of metabolic processes including anabolism and catabolism, as well as all the related cellular processes such as absorption, distribution, and detoxification of natural and xenobiotic materials, energy utilization, signal transduction, and regulation. Metabolome represents the current status of the cell or tissue.
Metabolome - a powerful portrait reflecting health, disease, ageing and the effects of drugs and the environment
ESA for Metabolomic Profiling
Two major challenges have been recognized in the field of Metabolomics: Incredibly large data sets make it difficult to find relevant data on marker compounds. The ESA Metabolomics System® addresses both problems by taking advantage of the central position of Redox Biochemistry in the biological process.
The Metabolomics System® utilizes the redox process much greater than MS or NMR. By nature, the Metabolomics System is a "relevance filter" that eliminates constitutive compounds and quantifies redox active components at high sensitivity.
Metabolomics® System
For Identification and Measurement of Physiologically Relevant Small Molecules
The ESA Metabolomics® System provides the ability to study a variety of molecules quickly and accurately:
- Measure Large Numbers of Molecules
- Simultaneously Assess and Measure Xenobiotics and their effects
- Compounds, Metabolites and Endogenous Compounds
- Compatible with Pattern Recognition Software
- Study Patterns of Individual Markers
ESA has applied its unique products and bioanalytical expertise to provide a new tool to easily measure a wide variety of physiologically relevant molecules. This system is compatible with both in vitro and in vivo experimental methods and can be used to simultaneously monitor both drug compounds and endogenous organic molecules.
Monitoring and Assessing the Molecular Response for Maintaining Proper Physiological Function
To fully understand and appreciate a biological system also requires an understanding of the small organic molecules (anti-oxidants, enzyme co-factors, cellular metabolites, vitamins, etc.) responsible for the maintenance of routine physiological functions. Changes in the levels of these molecules caused by disease or external stimuli can play an important role in the development or progression of disease and in adverse drug effects.
Applications for the ESA Metabolomics System
- Easily Identify and Quantify Potential Surrogate Marker Compounds
- Study the Multivariant Effects of External Stimuli on Biological Systems
- Identify and Measure the Effects of Even Small Perturbations Using In Vitro or In Vivo Biological Systems
- Rapidly Correlate and Recognize "Normal", "Diseased" and "Treated" Patterns of Molecules
- Easily Integrate Mass Spectrometry for Compound Identification
- Compatible with BioInformatics Software
The ESA Metabolomics® System consists of:
- A 16-channel CoulArray® Coulometric Array Detector for full Electrochemical Profiles
- Binary Gradient Solvent Delivery (dual - Model 582 Pumps)
- Cooled Autosampler (Model 542) with 84-96 sample capacity
- CoulArray for Windows-32® Software for full system control
- InfoMetrix Pirouette® Software for Principle Component Analysis and Pattern Recognition*
- Interface Hardware to MS and LC-MS
METABONOMICS
Metabonomics is a technique for examining dynamic changes in the Metabolome. This approach may be of utility in the Drug Discovery process. By profiling the Metabolome changes related to Xenobiotic intervention, it is possible to generate information about the overall systems response to such challenges.
The ESA Metabonomics® System can rapidly assess changes in the endogenous metabolite profile in response to external stimuli with high sensitivity and with discrimination that provides data on relevant molecules only.
ESA Coulochem III® for MS
For control of an electrochemical reactor placed in-line with your MS System
The Coulochem® III System for MS:
- Controls reaction cell potential
- Monitors resulting currents for reaction verification
- Controls external devices
- Functions in DC and Pulse modes
- Is compatible with any MS system
- Can be used as a high sensitivity electrochemical detector
ESA has created the Coulochem III® MS System as a platform to perform controlled electrochemical reactions on analytes in a flowing stream directly connected to a Mass Spectrometer.
The Coulochem III - MS System offers:
- Controlled electrochemical analyte reactions
- Enhanced ionization for greater sensitivity
- On-line nanosynthesis
- Rapid, high efficiency redox conversion
It helps us to:
- Study electrochemical processes
- Mimic biological redox processes
- Effect specific peptide/protein cleavage
- Characterize real-time homo and heterogenous electron transfer processes
- Aid in Drug Discovery and Early ADME/Tox
Electrochemical Ionization
Uncharged species will not produce a signal when using only mass spec. By adding an EC reactor on-line before the mass spec, molecules can be modified to produce an ion. This results in enhanced signal and lower limits of detection.
Soft Spots
Data produced with the EC-MS approach is useful in:
- Predicting molecular “soft spots”
- Aiding in predicting stability
- Guiding drug candidate selection
- Predicting metabolic activation and production of toxic metabolites.
