Introduction:
Cell proliferation, defense, suppression, and activation are all dependent on the minuscule chemicals or metabolites that are produced, absorbed, and altered by cultured cells, organs, tissues, and organisms. Hence the omics analysis of the small molecules is a dynamic technique in discovering and elucidating an organism's functions and responses. The versatility of metabolites can be seen in the fact that they not only function as the substrates or products of enzymatic processes but also function as regulators of the body's overall metabolism. The metabolome, constituting the complete set of metabolites found in a system and their interactions with the biological system, are the end product of gene expression. It accurately reflects the state of a disease at a given period as the changes in the metabolome occur rapidly. The metabolome provides a thorough and comprehensive picture of the phenotype. A high-throughput analytical technique called metabolomics identifies or evaluates all the metabolites present in the metabolomes of cells, biofluids, tissues, and organs. It has an indispensable role in systems biology. Metabolomics is a significant tool because it considers the fundamental metabolic activity and state of cells and tissues by measuring metabolites and their concentrations. The precise number of metabolites present in a human body is still difficult to determine because of the complexity of the metabolome, which has prevented thorough validation of a wide range of chemically varied molecules such lipids, carbohydrates, amino acids, nucleotides, and steroids. Metabolomics has proved to have a great number of applications in the field of biology specifically health and diseases. These include personalized medicine, oncology, clinical pharmacology, metabolic phenotyping, precision metabolomics, drug discovery, cancer metabolism among others.
History:
In the late 1940s, Roger Williams found out that each person's "metabolic profile" could be determined by the content of their biofluids. By using paper chromatography, he claimed that distinct metabolic patterns in saliva and urine were correlated to disorders like schizophrenia. The ability to quantify metabolic profiles statistically (as opposed to qualitatively) only became practical after the technical advances in 1960s and 1970s. Horning, et al. first employed gas chromatography-mass spectrometry [GS-MS] to analyse chemicals in human urine and tissue extracts in 1971, which led to the coining of the term "metabolic profile." David S. Wishart finished the initial version of the human metabolome on January 23, 2007. The first demonstration of real-time metabolome profiling took place in 2015.
Clinical Implications:
1.Metabolomics as a Biomarker in Oncology
Using conventional metabolomic techniques, it has been found that tumours have increased glycolytic capacity, high glutaminolytic function, and overexpression of the glycolytic isoenzyme pyruvate kinase type M2(M2- PK). They also have high phospholipid levels [characterized by an elevation of total choline-containing compounds (tCho) and phosphocholine], increased phosphocholine levels, and increased glycolytic capacity.
Due to the dominance of its inactive dimeric form in malignancies, M2-PK may be of particular relevance and can also be called as tumour M2-PK. Additionally, using NMR-based metabolomics of blood samples, it has been shown that lipid metabolic profiles are 83% accurate at differentiating between cancer patients and controls.
Notably, in vivo tCho determination by MRSI has successfully identified brain, prostate, and breast tumours and exhibits accordance with dynamic contrast enhanced-MRI diagnosis
2.Preeclampsia
Preeclampsia (PE), an intricate disorder that affects 3-5% of pregnancies, is a major cause of both maternal and foetal morbidity and mortality. Significant advancements in early PE prediction, diagnosis, and treatment have been severely constrained by the heterogeneity of clinical presentation, disease severity, and prognosis. With its ability to quantify identify low molecular weight substances (metabolites) in tissue and biological fluids, the rapidly emerging area of metabolomics holds great potential for improving our understanding of PE.
Conclusion:
The numerous properties and features of metabolomics techniques has made it a powerful tool in the aspects of research, human healthcare, and pharmaceuticals among others and has provided a deeper understanding about the same. Metabolomics has helped to find out informed results and helped tremendously in the decision making in case of biomarkers.
Metabolomics technology holds a lot of promise in ordinary clinical practice to support clinical judgements and to empower patients by providing a greater grasp of the dynamics of underlying disease.
References:
2.Gonzalez-Covarrubias,V.,Martínez-Martínez, E.,& Del Bosque-Plata, L. (2022). The Potential of Metabolomics in Biomedical Applications. Metabolites, 12(2), 194. https://doi.org/10.3390/metabo12020194
4.Spratlin, J. L., Serkova, N. J., & Eckhardt, S. G. (2009). Clinical applications of metabolomics in oncology: a review. Clinical cancer research: an official journal of the American Association for Cancer Research, 15(2), 431–440. https://doi.org/10.1158/1078-0432.CCR-08-1059
5.Benton, S. J., Ly, C., Vukovic, S., & Bainbridge, S. A. (2017). Andrée Gruslin award lecture: Metabolomics as an important modality to better understand preeclampsia. Placenta, 60 Suppl 1, S32–S40. https://doi.org/10.1016/j.placenta.2016.11.006