Metabolomics and Enzymology

Metabolomics had profound importance in recent years in context to its applications in the field of drug discovery and drug development. With recent advances in the field of metabolomics it can be proved as a major tool for innovative therapeutic discoveries. In the agricultural/chemical industry, metabolomics may be used to develop herbicides and pesticides. With increasing importance being placed on health and safety related aspects of our food, metabolomics can potentially be a valuable tool in food processing and quality control, or in plant breeding for improved crop varieties and in the development of novel food stuffs. Centre for Metabolomics is associated with therapeutic metabolomics. Computational immunology is a field of science that incorporates high-throughput genomic and bioinformatics ways to deal with immunology. 

Metabolic profiling is an assessment of low-molecular-weight metabolites and their intermediates in unicellular to multicellular biological systems that reflects the dynamic response to genetic modification.  The measurement and evaluation of the endogenous metabolite profile from a biological sample have provided many opportunities to investigate the changes induced by external stimuli. Metabolomic profiling has been used to recognize novel biomarkers and instruments of cardiovascular hazard. Metabolomic approach gives novel encounters into the robotic investigations of tumour diagnosis. Metabolic profiling can supplement routine frameworks and other "omics" propels in inquiring about preclinical prescription change issues.

The biological processes between different levels of “omics” are highly complex, a combined analysis of metaboliteand gene expression data will help discover and evaluate the underlying pathway mechanisms and identify genes that influence the metabolome. Transcriptomic studies measure the simultaneous expression of up to thousands of genes and can be used to identify which genes are up- or down-regulated under certain conditions. Metabolomic studies provide information on the metabolites found within a biological sample. These two branches seek to uncover the underlying systems biology and when combined they can be successful in predicting gene functions or identifying gene-metabolite associations.

The pivotal role of lipids in cell, tissue and organ physiology is demonstrated by a large number of genetic studies and by many human diseases that involve the disruption of lipid metabolic enzymes and pathways. Examples of such diseases include cancer, diabetes, as well as neurodegenerative and infectious diseases. So far, the outbreak of information in the fields of genomics and proteomics has not been matched by a corresponding advancement of knowledge in the field of lipids, which is largely due to the complexity of lipids and the lack of powerful tools for their analysis. Novel analytical approaches mainly LC and MS for system-level analysis of lipids and their interacting partners now make this field a promising area of biomedical research, with a variety of applications in drug and biomarker development. Mass spectrometry, largely due to its analytical power and rapid development of new instruments and techniques, has been widely used in lipidomics.

Metabolic modelling allows a deep insight into the molecular mechanisms of a particular organism. A reconstruction process breaks down metabolic pathways into their respective reactions and enzymes, and analyses them within the perspective of the entire network. It collects all the relevant metabolic information of an organism and compiles it in a mathematical model. A deep analysis of these reconstructed pathways can allow identification of key features of metabolism such as growth yield, resource distribution, network robustness, and gene essentiality. This information can then be applied to create novel biotechnological methods.

The latest addition of “omics” disciplines is Metabolomics and it has shown rapid growth in the application to human health research because of major advancements in measurement and analysis techniques. Metabolomics has unique advantages in systems biology and biomarker discovery. The next generation of analysis techniques promises even richer and more complete analysis capabilities that will enable earlier clinical diagnosis, drug refinement, and personalized medicine. The advancements in methodologies and statistical analysis that are enhancing and improving the performance of metabolomics is presented along with highlights of some recent successful applications

Conventional biological diagnostic procedures are based on a time-consuming series of sequential biochemical tests. The rise of “omic” technologies offers the complete picture of basic molecules that build a biological system at different levels. Metabolomics is the most recent “omic” technology based on biochemical characterization of metabolites and their changes pertaining to genetic and environmental factors. Metabolomics, when used as a translational research tool, can offer a link between the laboratory and clinic, and produce results in a lesser time.

Metabolomics is the examination of endogenous and exogenous low atomic mass metabolites inside of a cell, tissue, or biofluid of a life form in light of an outer stressor. Plant Metabolomics is to contemplate the plant framework at the sub-atomic level giving complete characterization of metabolome of plants under particular conditions. Using Metabolomics, a better understanding of the correlation between genes and the biochemical composition of a plant tissue in response to its environment can be obtained, and this information can be further used to assess gene function.

Metabolomics has been emerged as a significant tool in many disciplines. In food science, metabolomics has recently risen as a tool for quality, processing and safety of raw materials and final products. Nutrigenomics provides a gateway to study the effect of foods and food constituents on gene expression.  Applications of nutrigenomics include the genomic, transcriptomic, proteomic, and metabolomic studyof foods for compound profiling, authenticity related to food safety; the development of new transgenic foods, food contaminants, and whole toxicity studies; new investigations on food bioactivity, food effects on human health.

Metabolomics relies on a variety of bioinformatic tools aiming to derive information from data. Data acquisition with chromatography-coupled mass spectrometry yields high volumes of raw data that need to be processed to achieve proper biochemical data that eventually can be presented for statistics and pathway analysis in a coherent manner. A variety of new tools and algorithms have recently been developed that help in this process. If cutting-edge methods are used, we can confidently interpret signals that can neither be identified by reference standards and are used for novel researches.

To obtain holistic metabolic profiles from complex samples, such as biological fluids or tissue extracts, we require a powerful, high resolution and information rich analytical methods and for this, spectroscopic technologies are generally used. Mass spectrometry, coupled to liquid chromatography (LC–MS), is increasingly being used for such investigations as a result of the significant advances in both technologies over the past decade.

Xenobiotics are encountered by humans on a daily basis and include drugs, environmental pollutants, cosmetics, and even components of the diet. These chemicals undergo metabolism and detoxication to produce numerous metabolites, some of which have the potential to cause adverse effects such as toxicity. They can also block the action of enzymes or receptors used for endogenous metabolism or affect the efficacy of a co-administered drug. Therefore, it is essential to determine the full metabolic effects that these chemicals have on the body. Metabolomics, the comprehensive analysis of small molecules in a biofluid, can reveal biologically relevant perturbations that result from xenobiotic exposure. 

By studying the complete set of metabolites within a microorganism and monitoring its interactions between its development processes and the environment, metabolomics can potentially provide a more accurate picture of the actual physiological state of the cell. Microbial metabolomics has received much attention in recent years mainly because it supports and complements a wide range of microbial research areas from new drug discovery efforts to metabolic engineering.

Pharmacogenomics has some impact in clinical practice, through its use to select patient subgroups who will enjoy efficacy without side effects when treated with certain drugs. However, pharmacogenomics, has had less impact than initially predicted. One reason for this is that many diseases, and the way in which the patients respond to drug treatments, have both genetic and environmental elements. Pure genomics is almost blind to the environmental elements. A new methodology has emerged, termed pharmacometabolomics that is concerned with the prediction of drug effects through the analysis of pre-dose, biofluid metabolite profiles, which reflect both genetic and environmental influences on human physiology.

Metabolic syndrome is a cluster of physiological, biochemical, clinical, and metabolic factors that directly accelerates the risk of cardiovascular disease and diabetes mellitus. Insulin resistance, visceral adiposity, atherogenic dyslipidemia, endothelial dysfunction, genetic susceptibility, elevated blood pressure, hypercoagulable state, and chronic stress are the several factors which constitute the syndrome. Lifestyle modification remains the initial intervention of choice for such disorders. Modern lifestyle modification therapy combines specific recommendations on diet and exercise with behavioural strategies. The pharmacological and metabolomic datahelps in overcoming such problems.

Cancer cells are known to possess a highly unique metabolic phenotype. Hence development of specific biomarkers in oncology is necessary and they are used to detect the presence of cancer, determine prognosis, and/or assess the viability of treatment. Recent innovations have empowered the examination of numerous potential biomarkers and recharged enthusiasm for growing new biomarkers. Metabolomics allows for a global assessment of a cellular state within the context of the immediate environment, considering genetic regulation, altered kinetic activity of enzymes, and changes in metabolic reactions. Thus, Metabolomics is growing in the field of oncology with particular attention to its application as a biomarker in cancer diagnosis, assessing treatment effects, and in the development of novel therapeutics.