Cellular Metabolism And Techniques For Metabolomics Analysis

Metabolic Reactions and Their Regulation

1. A cell consists of various molecules or substances used during metabolic activity, known as metabolites catalyzed by various enzymes. Several factors explain the relationship between metabolites and the activity of enzymes as enzymes act as catalysts that control or regulate the rate of reaction or metabolic activity (Fernie, et al, 2012).This chemical transformation of one metabolite into another is also associated with the law of conservation and thermodynamics. Another factor is the kinetic property of enzymes that also affects the speed of metabolic activity. The nature of metabolic pathways can be understood through fluxes and how these fluxes affect the metabolite level (Fernie, et al, 2012). The theory explained by (Fell 2004) suggested that the small change in the activity of the enzyme and its effect on flux and metabolite concentration are predicted by the enzyme’s control coefficients. It explained that more than one flux value could be altered by the change in enzyme activity in the complicated or complex metabolic networks and cycle. Other control coefficients can be implied while there is an increase in enzyme activity in the metabolic network and directly decrease the flux elsewhere in the network. The theory suggested that a metabolomics study is a good option for detecting the effects of change in enzyme activity over the metabolite concentration ( 2004).

A large number of metabolic reactions involved in converting carbon sources into building blocks needed for macromolecular biosynthesis in the cellular body is known as cellular metabolism. Another simple explanation is that an increase in enzyme concentration will speed up the metabolic reaction as long as the substrate is available to bind and reaction velocity reaches the maximum. The metabolic fluxes change carbon sources by glycolysis and glycogenesis.  (Nielsen, 2003). A feedback loop maintains the variables in any reaction in the body; metabolic activities aid in regulating and maintaining the stable internal environment or homeostasis. When the enzyme activity increases, homeostasis fluxes the excess enzyme and maintains the metabolites' concentration. This procedure works as a feedback loop to keep the metabolic activities on the ideal level.

References

Fell, D. A. (2004) Enzyme s, metabolities and fluxes. Journal of Experimental Botany, Vol. 56, 267-272 

https://watermark.silverchair.com/eri011.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAsEwggK9BgkqhkiG9w0BBwagggKuMIICqgIBADCCAqMGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMtDY5xgJ2O7Dc1LDXAgEQgIICdKJ2QZKKUwbQ39i_C80qgQCwU4g6YGRwvpytsX4l6d3cjTd72bM3z3fXAMLsWukLnED_NirlBxFIxSuMdHLNd7qZmnCDuUiyzwRZ07QTfGnlLhCwDGUH-EmxojlwbzWGzdft0kOg19UM8Reg0CJcgG25elrM6RNL3uRnwVdiAw62gWnEQ9VBDVxx4dK0sJAlmU7QNP_N8MOgpXdnfKsthQn6-6j28hAMBOxHmwe3cWeK9NbxIOvNrw_1ch5AR4QzUovwwvEAMqHHr04LGYzah6qV689PLSKjfrl1Dwj14ht-9sE9oMBGwMrcgBHBLGx1F9LRxh85Hfhfg5DELDycFwBRp3y6YT0soUCB-hSMmm_gLQWzz0exF8CpKqDOh6jpnRIGvKoLGwfhBI2Q7AX0FvuK6VkD8a9TKi2BeZ39nU0FKEHOQcU0Q8L77kBZuZfodAClupbqr_Qa9B0WaxChXuT1PEM-Kkk2tNkihKzhE4gAmbt15TN3SXIQx__zCBluvfMcCPOi9GoRmgHWbZgoQ5jiLh_P-AVcD-KceOXZWZho9TU9d0tcf-LHq9Ywf7rBPH02GvNT5DzZFQzfWsCCXFiRHZJ6pDKaYjJjc69bXreDYy12MEG6ScAZiND0YFsnrpixoou6z9BmctqX4sXwJFQs1aPtwcMVNrDmK-jVpprIod2lYaMn6yWopd06u7-iQ3h17Mbbe9MNm0ik2x7jX66RRL_gG7-N82mkECkjzkxhh_EJUGOEci9n0PA9HDzVlbztS3e3BFLrg_XQZWiB0UiWHYlLT2b4BAijpZ7t0UvVxc0wNPPTyPreN40Hgwj6VWJ7Coc

Fernie, A.R., Stitt, M. (2012). On the Discordance of Metabolomics with Proteomics and Transcriptomics: Coping with Increasing Complexity in Logic, Chemistry, and Network Interactions Scientific Correspondence, Plant Physiology, Volume 158,(3),1139–1145. 

https://academic.oup.com/plphys/article/158/3/1139/6109138

Nielsen J. (2003). It is all about metabolic fluxes. Journal of bacteriology, 185(24), 7031–7035. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC296266/

The wide study of the metabolites that are commonly detected in an organisms bodily fluids, cell or tissue samples are known as metabolomics. Metabolites are the final product of genomic, transcriptomic, and proteomic perturbations, and global metabolomics analysis has developed new aspects in various scientific research (Johnson & Gonzalez 2012). The various advantages of using models bring a potential improvement in diagnosis treatment, and aftercare of the disease as the research can never be directly done on human beings. Thus, using model organisms that have similar genomes can be helpful in the treatment. Using models like the transgenic mouse, new technology, and experimental design is quite helpful in predicting the treatment response and survival (Johnson & Gonzalez 2012). The field of metabolomics has potential applications in the evolution of healthcare and biomedical sciences, the emerging field of drug discovery and personalized medicine in health care.

The various challenges of metabolomics analysis are interindividual variations, instrumentation choice, identification of biomarkers, and developing an appropriate model for experimental studies. In the preclinical phase, the most important challenge that the researcher faces is to analyse a large number of genetic interindividal variations. It has been found that the metabolomes are influenced by various environmental factors like diet, stress, and lifestyle and genetic factors like gender and gene polymorphisms (Kosmides, et al., 2013). The concept of metabolic fingerprinting is used to identify the variation in an individual, as it is found that there is a great genetic difference between mice and humans; thus transgenic mouse model was created to develop and establish a human microbiome within the mouse to overcome interindividual variations. The other challenge is choosing effective instrumentation as there are various common metabolomics analysis tools like NMR spectroscopy, Mass spectroscopy, GC-MS and UHPLC-MS. Choosing a single analysis tool to reveal whole metabolites (Kosmides, et al., 2013). The third challenge is identifying biomarkers and conformation of these markers, which is the most important step of metabolomics investigation. Various databases provide identification of metabolites, but there is an essential need to standardize the personal and professional methodology for metabolomics application; thus, authentic reports and data can be stored in the databases and metabolomics laboratories (Kosmides et al. 2013).

References

Johnson, C. H., & Gonzalez, F. J. (2012). Challenges and opportunities of metabolomics. Journal of cellular physiology, 227(8), 2975–2981. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309313/

Kosmides, A. K., Kamisoglu, K., Calvano, S. E., Corbett, S. A., & Androulakis, I. P. (2013). Metabolomic fingerprinting: challenges and opportunities. Critical reviews in biomedical engineering, 41(3), 205–221. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096240/