Metabolomics and metabolism

It is a complete set of small-molecule of less than 1.5 k/Da metabolites such as metabolic intermediates, hormones, other signaling molecules and secondary metabolites to be found within a biological sample, as a individual organism. The first metabolite database called METLIN for searching fragmentation data from tandem mass spectrometry experiments was conducted by the members of Gary Siuzdak’s lab at The Scripps Research Institute located in united states of America in 2005.

In biochemistry, a metabolite is an breakdown or end product of metabolism and makes energy and are usually used for small molecules, which are combined to form a large molecule in a cell. It may have functions like fuel, structure, signaling, restorative and inhibitory actions on enzymes. A co-factor to an enzyme are pigments, odorants, and pheromones. Generally Metabolites are of two types such as primary metabolite and secondary metabolite. Primary metabolite helps in growth, development and reproduction of a cell whereas secondary metabolite is not involved directly in those process but shows ecological balance. Ethylene exemplifies a primary metabolite; Antibiotics and Pigments such as Resins and Terpenes exemplifies a secondary metabolite.

It  is defined as "the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification". The word originated from the Greek language which shows “meta” meaning change and “Nomo”  meaning a rule set or set of laws. It provides detailed information on the procedures involved in nuclear magnetic resonance (NMR) spectroscopy, gas chromatography-mass spectrometry (GS-MS), liquid chromatography-mass spectrometry (LC-MS), and capillary electrophoresis-mass spectrometry (CE-MS).

It is the study of extracellular metabolites and   use many techniques from other subfields of metabolomics, and has applications in biofuel development, bioprocessing, determining drugs mechanism of action, and studying intercellular interactions so It is also called as metabolic foot-printing.

It is defined as the identification and quantification of a selected number of predefined metabolites in a specific metabolic pathway and is the measurement in biological systems of the components with low molecular weight metabolites and their intermediates or end products is called Metabolic profiling.

It is a rapid and noninvasive analysis, representing a powerful approach for the characterization of phenotypes and the distinction of specific metabolic states due to environmental alterations. Research of unbiased, rapid, global analysis of samples to provide sample classification is oriented towards deriving clinically relevant differences rather than identifying all the molecules present in a sample. The physiological and metabolic modifications in the acute liver damage rat were investigated by performing a metabolic analysis in metabolic fingerprinting.

The metabolomics which deals with an essentially comprehensive, nonbiased, high-throughput analyses of complex metabolite mixtures typical of plant extracts is called Plant Metabolomics. The First International conference on Plant Metabolomics was held at Wageningen, The Netherlands, in April 2002. The Resources for plant metabolomics are segregating populations like DHs, RILs, etc and Genetic stocks and Mutant lines. They show some maps from molecular genetic maps to physical maps and then to Genome Sequencing. QTL analysis Is used foe molecular genetic mapping only whereas Functional genomics in genome sequencing for discovery of genes and markers.

Metabolomics is novel platform that offers huge potential for the diagnosis and prognosis of neurodegenerative disorders  as an individual metabolome reflects alterations in genetic, transcript, and protein profiles and effects from the environment. Analysis may also be able to align the choice of therapy, identify responders and predict toxicity, paving the way to a customized therapy. It classify some diseases in human metabolism and affects the system of the body such as

• Metabolomics in Neuropsychiatric Disorders
• Metabolomics in Metabolic Disorders:
• Metabolomics studies in Rheumatoid Arthritis:
• Metabolomics in Cardiovascular Diseases
• Metabolomics in Nephrology
• Metabolomics studies in Osteoarthritis:
• Metabolomics studies in Gouty Arthritis

It is a technique used to collect the samples from tissue, plasma, saliva, urine, etc. after that sample undergone preparation with the metabolites and their components. Sample analysis is analyzed and quantified by either NMR Spectroscopy or MS Spectroscopy are coupled with Liquid chromatography or Gas chromatography. Then the raw output data undergone Data Acquisition and further followed by data analysis and interpretation E.g.: Multivariate analysis – PCA with score plot and loading plot. Analytical techniques involves two types of methods, they are a) Separation Methods   b) Detection Methods.

NMR Spectroscopy based Metabolomics provides an  intend to classify progression of toxicological actions, monitor the onset of action and organ-specific toxicity, and identify prodrugs of toxicity. The relative ease of sample preparation, its ability to quantify metabolite levels, the high level of experimental reproducibility, and the inherently nondestructive nature of NMR spectroscopy have made the platform for large-scale clinical studies. It will also explore some of the specific strengths of NMR-based metabolomics, particularly consider about isotope selection or detection, mixture of de-convolution via 2D spectroscopy, automation, and the ability to non-invasively analyze vernacular tissue specimens. It can be used for both targeted and untargeted analyses, but it is not commonly used for targeted analyses.

This metabolomics offers quantitative analysis with a high selectivity and sensitivity with a  potential to identify the metabolites. Different ionization techniques are obtained to maximize the number of detected metabolites. Both (GC)-MS and (LC)-MS are superior for targeted analyses. In in-vivo studies , desorption electrospray ionization (DESI) may be a useful way to analyze tissue samples during surgery, MS is not used for in vivo metabolomics studies. The main chromatography techniques that are specifically coupled with MS are HPLC, gas chromatography, and capillary electrophoresis (CE). For example, investigations detailing a number of diseases including breast cancer, colorectal cancer, prostate cancer, esophageal and gastric cancer, cardiovascular diseases, kidney diseases , inborn errors of metabolism.

It is an progressing field of scientific endeavor that merges immunology and metabolism and has provided valuable context when evaluating the influence of dietary interventions on exercise-induced immune dysfunction

It can be categorized into two types based on their analytical approaches are Targeted and  Untargeted groups.  It is having a segmentation on the metabolic profiling, identification, quantification on the metabolic substrates either by targeted or untargeted approaches. 

A)Targeted metabolomics

• It is a type of metabolomics which defines absolute metabolite concentrations and identification of specific metabolites by association between their state of condition.                                             

B)Untargeted   Metabolomics

• ​It is also a type of metabolomics analytical approach associated with a disease state between samples don’t require any prior knowledge in between   metabolite concentration and disease states.

It is stated that the chemical reactions in the body's cells that change food into energy in which the above described set of reactions within the cells is called intermediary metabolism or intermediate metabolism These enzyme-catalyzed reactions allow organisms to grow and reproduce, maintain their structures, and respond to their environments. The major elements are available  in the form of carbohydrates, lipids, and proteins. In addition, vitamins, minerals, fatty acids and water are necessary to a living organism. It is further classified into two categories i.e.; Catabolism and Anabolism. The conversion of the energy from food into ATP form of energy. The conversion of food to constructive blocks of carbs, proteins, nucleic acids, lipids and finally the elimination of metabolic wastes are the three main purposes of metabolism.

It is a biochemical processes responsible for the metabolic formation, breakdown, and inter-conversion of energy in ATP form of a human beings. The constant supply of energy by carbohydrate is only Glucose which can be broken down via glycolysis, enter into the Krebs’s cycle and oxidative phosphorylation to generate ATP. Carbohydrates are available in three forms such as sugar, starch, cellulose. Starches and sugars form  essential sources of energy for humans whereas Fibers or cellulose contribute to bulk in diet. Body tissues depend on glucose for all activities in a day to day life. Foods such as rice, wheat, bread, potatoes are mostly having high content of sugar. The overall reaction after food intake is in the form of a chemical reaction is   C₆H₁₂O₆  + 6O₂→6 CO₂  +  6 H₂O + energy

Protein metabolism is a biochemical processes responsible for the catabolism of proteins and anabolism  of proteins from amino acids (breakdown and formed). Proteins are the main tissue builders in the body. It helps in structure, functions, hemoglobin formation to carry oxygen, enzymes to carry out vital reactions of a cell and innumerable functions in the body. It helps in maintenance of proper PH and fluid balance. The best quality protein foods are eggs, milk, soybeans, meats, vegetables, and grains. They are necessary for nutrition because they contain amino acids. Among the 20 amino acids, the human body is unable to synthesize  8 and these are called essential aminoacids. The essential aminoacids include: Isoleucine, Lysine, Threonine, Phenylalanine, Leucine, Tryptophan, Methionine, Valine.

Fat metabolism is a biological metabolic process that breaks down ingested fats into fatty acids and glycerol after that a simple compound is derived, which can be used in cells of the body. Fats are the sources of energy. They produce double energy as either carbohydrates or protein on a weight basis. The end products of fat metabolism is carbon-dioxide, water and ATP.

The functions of fats include:

• It helps to form a cellular structure
• It provides a protective cushion and insulation around organs which are vital.
• Helps to absorb fat-soluble vitamins
• Providing a reserve storage for energy

Essential fatty acids include saturated fatty acids like   myristoleic acid, palmitoleic acid, sapienic acid, oleic acid, and unsaturated fatty acids like linoleic, linolenic, and arachidonic acids and need to be taken in diet.

A)MINERALS

The minerals in food we taken  do not release  energy directly in the body  but are important as body regulators and plays a role in metabolic pathways of the body. More than 50 elements are found in the human body in that about 25 elements have been found to be as  essential for the human body. Important minerals include: Calcium, Phosphorus, Iron, Sodium, Potassium, Chloride ions, Copper, Cobalt, Manganese.

B)VITAMINS

Vitamins are functional parts of enzymes involved in energy release and storage. The liver is mostly involved in vitamin metabolism and it produces bile for absorption of fat-soluble vitamins (A, D, E, K), and used for vitamin storage. Vitamins are important in metabolism include: Vitamin A, Vit-B2 (riboflavin), Niacin or nicotinic acid, Pantothenic Acid, Thiamine, Folate, Cyanacobalamine.

The regulation of metabolic reactions in the cancer cell or the surrounding  stroma  generate intermediates that are at the key of cancer pathogenesis, progression, and therapy resistance. Tumours exhibit a wide range of  varieties in molecular alterations that merge in metabolic reprogramming. Warburg’s work focused on the metabolic reprogramming of cancer cells, which is now consider as one of the hallmarks of cancer as put forward by Douglas Hanahan and Robert Weinberg in Hallmarks of Cancer. The metabolic profile observed in cancer cells often shows increased consumption of glucose and glutamine, increased glycolysis, alterations in the use of metabolic enzyme isoforms, and increased secretion of lactate. The hallmarks of cancer are Deregulated cellular energetics, sustaining proliferative signaling, Evading growth suppressors, Avoiding immune destruction, Enabling replicative immortality, Tumour promoting inflammation, Resisting cell death.

It is the sequence of enzyme catalyzed reactions that lead to the conversion of a substance into a final product is called as Metabolic Pathways. These allow some enzymes for conversion of energy by different chemicals in a pathway. Enzymes are vital to metabolism because they allow organisms to operate desirable reactions that require energy for growth, production and maintenance. These reactions also are coupled with those that release energy may be in the form of ATP. As enzymes act as catalysts they allow these reactions to proceed rapidly and effectively. Enzymes also allow the regulation of metabolic pathways in response to changes in the cell's environment and signals to other cells. Metabolism introduces some major properties, they are:

• Carbon fixation
• Folic acid metabolism and human embryopathy
• Nutrient utilization in humans
• Metabolism Pathways
• Energy metabolism
• Oxidative Phosphorylation: mechanism of ATP synthesis.   

This syndrome is a combination of conditions that occur together by increasing your risk of heart disease, stroke and Type 2 diabetes and worsen the situation. These conditions may increases blood pressure, high blood sugar levels, excess body fat content around the waist, and abnormal cholesterol or triglyceride levels in the body.

Types of disorders:  It leads to variety of disorders by their physical and chemical nature, onset of action, physiological effects, pathophysiology.

•  Original metabolic disorder
•  Silent metabolic disorder
•  Acute metabolic disorder
•  Neurological disorder
•  Inherited disorder

It is distinguished by elevated levels of the amino acid valine in the blood and urine caused by deficit of the enzyme valine transaminase. This enzyme is needed in the breakdown of valine, this condition is called as Valinemia  which is a very rare metabolic disorder.

The metabolic disorders are affected due to abnormal level of substrates present in the body and leads to different disorders and it is treated with the help of some below mentioned characters.

• Self-care
• Physical exercise
• Primary care Provider (PCP)
• Anti-diabetic medication
• Cardiologist
• Nutritionist