CHAPTER 3 - Molecular basis of clinical metabolomics

GOMEZ CASATI, DIEGO F.; BUSI, MARÍA V.

Clinical Molecular Medicine: Principles and Practice

ELSEVIER

Año: 2020; p. 47 - 55

Metabolomics, the comprehensive high-throughput analysis in which all the metabolites in a biological system are identified and quantified [1,2], has emerged as a functional genomics methodology which helps to better understand the complex molecular interactions in biological systems [3]. Metabolomics strategies are closely related to other omics, such as genomics, transcriptomics, and proteomics, because it represents the logical progressionfrom large-scale analysis of nucleic acids and proteins at the systems level [4,5]. Recently, metabolomics became essential as a tool in medicine, with an important role in the diagnosis and prevention of numerous diseases and in the design of strategies to carry out an adequate treatment for each pathological condition [6]. Metabolomics allows us to evaluate the physiological state of a cell in the context of its environment and considering the modification of enzyme kinetics and changes in metabolic reaction rates [79]. Thus compared withgenomics or proteomics, metabolomics reflects changes in phenotype and therefore function. The “omic” sciences are, however, complementary as “upstream” changes in genes and proteins are measured “downstream” as changes in cellular metabolism [7,10,11]. Other features of metabolomics are similar to those of proteomics and transcriptomics, including the ability to assay biofluids or tumor samples and the relatively inexpensive, rapid, and automated techniques once start-up costs are taken into account. Metabolites are the end products of the different cellular processes. Metabolite levels are related to the response of biological systems to changes in genetic and/or physiological conditions or environmental changes. On the other hand, the metabolome refers to the complete set of metabolites that are present in a biological system which participates in biochemical pathways required for its normal function [1,12]. Thus metabolomics is considered the ultimate level of postgenomic analysis because it can reveal changes in metabolite levels that are controlled by only minor changes in gene expression measured using transcriptomics techniques and/or by analyzing the proteome that could reveal posttranslational control mechanisms on enzyme activity [13]. In the last years, metabolomics has not only been used for medical applications but also an extensive research on metabolomics was carried out in many organisms, such as bacteria, fungi, parasites, and plants, because they produce a vast chemical diversity of compounds that may be beneficial for humans, including food, pharmaceuticals, and industrial raw materials [14]. This chapter describes different applications of metabolomics in clinical and medical practice, such as the identification and use of markers related to genetic inborn errors, the use of markers for the diagnosis, prevention, prognosis, and treatment of different human diseases, such as cancer, heart diseases, and neurological pathologies, and for the study and diagnosis of mitochondrial diseases.