Metabolomics- concepts and applications

Metabolomics is the large-scale study of small molecules, commonly known as metabolites, within cells, biofluids, tissues or organisms. Collectively, these small molecules and their interactions within a biological system are known as the metabolome.
Metabolomics is an analytical profiling technique for measuring and comparing large numbers of metabolites present in biological samples. Combining high-throughput analytical chemistry and multivariate data analysis, metabolomics offers a window on metabolic mechanisms.

1. IIT- BHU Department of Pharmaceutical Engineering And Technology “METABOLOMICS” -CONCEPTS, APPLICATIONS AND RECENT ESTABLISHMENT Submitted to Dr. S. Hemalatha Professor, IIT- BHU Submitted by- Anup Kumar Ray M.Pharm . 2 nd Semester

2. WELCOME

3. Contents Introduction Terminologies Concepts Applications Recent event References

4. INTRODUCTION

5. Before the arrival of molecular medicine, unraveling the mechanisms of disease was essentially a biochemical endeavor. Different studies highlighted important concepts about chemical individuality and led to simple diagnostic tests, dietary interventions, and treatments for various diseases. In this current age of molecular medicine, it is now within the reach of most laboratories to investigate the structure and functional expression of genomes on a global scale.

6. However, the study of proteins at a global level, proteomics, has not yet achieved such widespread use. In contrast, metabolomics is emerging as a field with tremendous promise in extending ‘‘omics’’ from the gene to the small molecule. Metabolomics is a newborn cousin to genomics and proteomics. Specifically, metabolomics involves the rapid, high throughput characterization of the small molecule metabolites found in an organism.

7. Since the metabolome is closely tied to the genotype of an organism, its physiology and its environment, metabolomics offers a unique opportunity to look at genotype-phenotype as well as genotype- envirotype relationships. Metabolomics is increasingly being used in a variety of health applications including pharmacology, pre-clinical drug trials, toxicology, transplant monitoring, newborn screening and clinical chemistry.

8. TERMINOLOGIES

9. ‘OMICS’ Technologies that measure some characteristic of a large family of cellular molecules, such as genes, proteins, or small metabolites, have been named by appending the suffix “-omics,” as in “genomics.”  Omics  refers to the collective technologies used to explore the roles, relationships, and actions of the various types of molecules that make up the cells of an organism.

10. Fig 1. O mics technology

11. Metabolism Metabolism is the ensemble of chemical transformations carried out in living tissue ; operationally it is embodied in the matter and energy fluxes through organisms. Metabolites Metabolites are the substrates, intermediates and products of metabolism. Metabolome The  metabolome  forms a large network of metabolic reactions, where outputs from one enzymatic chemical reaction are inputs to other chemical reactions. Such systems have been described as hypercycles.

12. Metabolomics Metabolomics is defined as the measurement of the amounts (concentrations) and locations of the all the metabolites in a cell, the metabolites being the small molecules (e.g., glucose, cAMP,1 GMP,2 glutamate, etc.) transformed in the process of metabolism (i.e., mostly the substrates and products of enzymes)

13. Metabonomics Metabonomics is defined as the quantitative measurement of the multiparametric metabolic responses of living systems to pathophysiological stimuli or genetic modification, with particular emphasis on the elucidation of differences in population groups due to genetic modification, disease, and environmental (including nutritional) stress. The word origin is from the Greek meta meaning change and nomos meaning a rule set or set of Laws.

14. Exometabolomics Exometabolomics , or "metabolic footprinting ", is the study of extracellular metabolites. It uses many techniques from other subfields of metabolomics, and has applications in  biofuel  development,  bioprocessing , determining drugs' mechanism of action, and studying intercellular interactions.

15. CONCEPTS

16. C oncept Of M etabonomics A nd M etabolomics

17. C oncept O f M etabolites

18. Metabolites are the intermediates and products of metabolism. A metabolite is usually defined as any molecule less than 1 kDa in size. However, there are exceptions to this depending on the sample and detection method. For example, macromolecules such as lipoproteins and albumin are reliably detected in NMR-based metabolomics studies of blood plasma. In plant-based metabolomics, it is common to refer to "primary" and "secondary" metabolites.

19. Concept of metabolites Cont.. A primary metabolite is directly involved in the normal growth, development, and reproduction. A secondary metabolite is not directly involved in those processes, but usually has important ecological function. Examples include antibiotics and pigments. By contrast, in human-based metabolomics, it is more common to describe metabolites as being either endogenous (produced by the host organism) or exogenous.

20. Concept of metabolites Cont.. Metabolites of foreign substances such as drugs are termed xenometabolites . The metabolome forms a large network of metabolic reactions, where outputs from one enzymatic chemical reaction are inputs to other chemical reactions. Such systems have been described as hypercycles

21. Fig. 2. K ey S tages of a M etabolomics S tudy

22. Fig. 3. K ey S teps of a P lant M etabolomics S tudy.

23. Fig. 4. M etabonomics T ypical S trategy

24. Software List For Metabolomic Analysis

25. APPLICATIONS

26. Key applications Toxicity assessment/toxicology. Metabolic profiling (especially of urine or blood plasma samples) can be used to detect the physiological changes caused by toxic insult of a chemical (or mixture of chemicals). In many cases, the observed changes can be related to specific syndromes, e.g. a specific lesion in liver or kidney. This is of particular relevance to pharmaceutical companies wanting to test the toxicity of potential drug candidates: if a compound can be eliminated before it reaches clinical trials on the grounds of adverse toxicity, it saves the enormous expense of the trials.

27. Key applications cont.. Functional genomics. Metabolomics can be an excellent tool for determining the phenotype caused by a genetic manipulation, such as gene deletion or insertion. Sometimes this can be a sufficient goal in itself—for instance, to detect any phenotypic changes in a genetically-modified plant intended for human or animal consumption. Nutrigenomics It is a generalized term which links genomics, transcriptomics , proteomics and metabolomics to human nutrition.

28. Key applications cont.. In general a metabolome in a given body fluid is influenced by endogenous factors such as age, sex, body composition and genetics as well as underlying pathologies. The large bowel microfloras are also a very significant potential confounder of metabolic profiles and could be classified as either an endogenous or exogenous factor. The main exogenous factors are diet and drugs. Diet can then be broken down to nutrients and non- nutrients. Metabolomics is one means to determine a biological endpoint, or metabolic fingerprint, which reflects the balance

29. CONCLUSION The experimental results suggest that Corydalis yanhusuo alkaloid CA can effectively cure the gastric ulcer, particularly the middle dose group. It seems that there is a marked overlap among the neuronal pathogenetic pathways involved in ulcer genesis and depression. Therefore, it is not surprising that medication for the treatment of depressive episodes can also exert potent protective effect against gastric ulcer

30. As a systems approach, metabolomics could systematically identify and quantify or reveal novel differentiating metabolites for disease that may provide diagnostic biomarkers and/or monitoring tools as well as insight into potential targets for disease therapy and prevention. In this study, the metabonomics based on the GC-MS technique and the metabolism network analysis were applied to investigate metabolic changes and biomarkers in epileptic patients. The work not only enhances the understanding of the pathology of epilepsy, but also provides an experimental foundation for the therapeutic strategy of epilepsy. Furthermore, this work demonstrated the powerful predictive potential of the metabolism network analysis to neurological disease.

31. CONCLUSION The full elucidation of biochemical and genetic mechanisms underlying plant developmental and stress responsive biology depends largely on the comprehensive investigations using systematic omics techniques, which is the foundation for the application of metabolomics in plant science. Among them metabolomics is of particular importance, because the metabolites are more relevant to the plant phenotype (both physiological and pathological phenotypes) as compared with DNAs, RNAs or proteins

32. Conclusion 1H-NMR-based metabolomics analysis of urine samples showed some metabolism alteration involved in diabetes. Such altered metabolic pathways were glycolysis, Krebs cycle, protein and creatine metabolism. The administration of M. charantia fruits extract was able to partially fix the altered metabolism of diabetic rats as indicated by the shifting of some metabolites profile (glucose, succinate, lactate, creatine, creatinine, urea and phenylacetylglycine) to normal level. Hence, this extract demonstrated to be potential anti-type 1 diabetic agent, as it able to alter the main pathway leading to diabetic condition in treated rats although not all metabolites were shifted to normal level.

33. R E C E N T E S T A B L I S H M E N T

34. SUMMARY Early detection and effective treatment of severe COVID-19 patients remain major challenges. Here, they performed proteomic and metabolomic profiling of sera from 46 COVID-19 and 53 control individuals. They, then trained a machine learning model using proteomic and metabolomic measurements from a training cohort of 18 non-severe and 13 severe patients. The model was validated using 10 independent patients, 7 of which were correctly classified.

35. Targeted proteomics and metabolomics assays were employed to further validate this molecular classifier in a second test cohort of 19 COVID-19 patients, leading to 16 correct assignments. They identified molecular changes in the sera of COVID-19 patients compared to other groups implicating dysregulation of macrophage, platelet degranulation , complement system pathways, and massive metabolic suppression. This study revealed characteristic protein and metabolite changes in the sera of severe COVID-19 patients, which might be used in selection of potential blood biomarkers for severity evaluation.

36. REFERENCES

37. Salem, M.A., Perez de Souza, L., Serag , A., Fernie , A.R., Farag , M.A., Ezzat , S.M. and Alseekh , S., 2020. Metabolomics in the Context of Plant Natural Products Research: From Sample Preparation to Metabolite Analysis.  Metabolites ,  10 (1), p.37. Shen , B., Yi, X., Sun, Y., Bi, X., Du, J., Zhang, C., Quan , S., Zhang, F., Sun, R., Qian , L. and Ge , W., 2020. Proteomic and Metabolomic Characterization of COVID-19 Patient Sera. Tianjiao , L., Shuai , W., Xiansheng , M., Yongrui , B., Shanshan , G., Bo, L., Lu, C., Lei, W. and Xiaorong , R., 2014. Metabolomics coupled with multivariate data and pathway analysis on potential biomarkers in gastric ulcer and intervention effects of Corydalis yanhusuo alkaloid.  PloS one ,  9 (1).

38. Wei, C., Li, Y., Yao, H., Liu, H., Zhang, X. and Guo , R., 2012. A metabonomics study of epilepsy in patients using gas chromatography coupled with mass spectrometry.  Molecular Biosystems ,  8 (8), pp.2197-2204. Tyagi , S., Raghvendra , S.U., Kalra , T. and Munjal , K., 2010. Applications of metabolomics-a systematic study of the unique chemical fingerprints: an overview.  Int. J. Pharm. Sci. Rev. Res ,  3 (1), pp.83-86. Perumal , V., Murugesu , S., Lajis , N.H., Khatib , A., Saari , K., Abdul- Hamid , A., Khoo , W.C., Mushtaq , M.Y., Abas , F., Ismail, I.S. and Ismail, A., 2015. Evaluation of antidiabetic properties of Momordica charantia in streptozotocin induced diabetic rats using metabolomics approach.

39. Bino , R.J., Hall, R.D., Fiehn , O., Kopka , J., Saito, K., Draper, J., Nikolau , B.J., Mendes, P., Roessner-Tunali , U., Beale, M.H. and Trethewey , R.N., 2004. Potential of metabolomics as a functional genomics tool.  Trends in plant science ,  9 (9), pp.418-425. Hong, J., Yang, L., Zhang, D. and Shi, J., 2016. Plant metabolomics: an indispensable system biology tool for plant science.  International journal of molecular sciences ,  17 (6), p.767. Tan, S.Z., Begley, P., Mullard , G., Hollywood, K.A. and Bishop, P.N., 2016. Introduction to metabolomics and its applications in ophthalmology.  Eye ,  30 (6), pp.773-783. https://en.wikipedia.org/wiki/Metabolomics

40. T h a n k Y o u