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.
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Metabolomics- concepts and applications
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. 2nd Semester
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.
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.
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.
19. 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.
20. 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.
21. 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
28. 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.
29. 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.
30. 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
31. 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
32. 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.
33. 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
34. 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.
37. 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.
38. 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.
40. 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
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41. Wei, C., Li, Y., Yao, H., Liu, H., Zhang, X. and Guo, R., 2012. A
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Hamid, A., Khoo, W.C., Mushtaq, M.Y., Abas, F., Ismail, I.S. and Ismail,
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in streptozotocin induced diabetic rats using metabolomics approach.
42. 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
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https://en.wikipedia.org/wiki/Metabolomics