Metabolomics

Metabolomics

ιατρική ακριβείας

What is Metabolomics Analysis?

Metabolism is inextricably linked to health and human disease.

The high-quality representation of metabolism at the genome scale, i.e. in a way that captures the interaction between metabolites, is for systems biology the key to understanding the entire network of metabolic reactions presented by an organism.

Metabolomics represents the revolutionary approach to research, since it focuses beyond simple pathways, to holistic investigation that tries to capture the complexity of metabolic networks.

We often hear about metabolism and its importance to our health, but how much do we really know what that importance is?

If we want to give a definition of metabolism, we should start from the  cell . The cell is a complex biological system, consisting of various subsystems which we call  organelles . The function of the cell is based on chemical reactions which we call  cellular biochemistry . These take place in all parts of the cell, either in the cytoplasm or in the nucleus, and make up the process we call  metabolism  (Figure 1, catabolism and anabolism).

Figure 1.  Map of the metabolic pathways known to date in the human cell while demonstrating the complexity of the chemical reactions that take place inside the cell to form metabolites (Harvard Health Magazine, May – June 2011).

But why is metabolism so important? Because understanding metabolism is fundamental to understanding the phenotypic behavior (i.e. morphological, productive, ethological, etc. characteristics)  of all living organisms, including humans, where  metabolism is inextricably linked to health and human diseases .

The high-quality representation of metabolism at the genome scale, i.e. in a way that captures the interaction between metabolites, is for systems biology the key to understanding the entire network of  metabolic reactions  presented by an organism. These reactions are divided into  catabolic ones , which involve the  breakdown of complex substances into simpler ones with a parallel, usually, energy yield (exothermic) and  anabolic ones , which involve the synthesis of complex chemical substances, for the realization of which energy is usually consumed  ( endothermic). To achieve this, each cell works with  catalysis  and  cofactors , which are metabolites, which are formed during the process of catabolism and anabolism.

The  catalytic  activity of many  enzymes  depends on the presence of small molecules called  cofactors , although the exact role varies, depending on the cofactor and the enzyme. An enzyme without its cofactor is called an apoenzyme. The fully catalytically active enzyme is called holoenzyme.

Cofactors can be subdivided into two categories:  metals  and  small organic molecules .

The scientific term “omics” refers to a group of analytical methodologies that aim to characterize and quantify biological molecules. These are genes (DNA), the various forms of RNA (called transcripts), proteins and metabolites. The combination of all the above are translated and give the structure, function and dynamics of cells, tissues or organisms.

Genomics  , for example , is described as the analysis of the structure and function of DNA. Accordingly,  proteomics  includes the systematic study of proteins to investigate the structure, function and regulation of biological systems.

Metabolomics represents the revolutionary approach to research, since it focuses beyond simple pathways, to holistic investigation that tries to capture the complexity of metabolic networks.

From gene expression to phenotype: What the ‘omics’ tell us and how they interact with each other.

More specifically, metabolomics is the study of the metabolic profile of small molecules within a biological organism. The term  metabolome  defines the entire set of metabolites present in a cell, tissue, organ or organism and represents all the end products of cellular processes.

That is, metabolomics provides a functional view of an organism, as it is determined by the set of its genes, its RNA, its proteins and environmental factors, such as e.g. diet, and medications. For this reason it is often used by systems biology as a tool for the development of new drugs.

This analysis aims to reveal how micronutrient deficiencies and sufficiency can affect multiple biological processes, leading to health maintenance or disease progression.

Representing this knowledge as a network is key to understanding the multiple and broad interactions between cofactors and proteins. The relationships between interacting cofactors and proteins (and by extension genes) and diseases may provide strategies for targeted nutritional intervention in various phenotypes.

A look at the diagram below (Figure 3) is probably confusing to a non-expert. However, this image, reminiscent of a tangled tangle, is perfectly representative of the work that metabolomics does! He tries to untangle the “entanglement”, which is the connection of the co-factors with the various diseases and by catching the… end of the thread, lead to the treatment of the diseases.

Figure 3 . Cofactors (shown in the image as the circles on the right and left sides) are associated with a GWAS (genome wide association study) disease (the squares in the center of the image) if the protein associated with the given disease interacts with the cofactors -goals. Diseases are color-coded according to the percentage of GWAS proteins interacting with cofactors and ranked according to their relevance (ascending order from top to bottom). Edges are weighted according to the number of GWAS proteins that require that particular cofactor.

It is important to note that many more interacting protein cofactors than proteins are expressed in many tissue types. Proteins that interact with specific factors, mainly organic vitamins, tend to be co-expressed in all human tissues, which could lead to the conclusion that they are controlled by a similar system of absorption, distribution, metabolism and excretion processes.