Skip to 0 minutes and 5 secondsWARWICK DUNN: Metabolomics is a non-biased experimental approach that attempts to measure all of the metabolites in the biological sample. Although the approach is designed to be non-biased, no single analytical technique or even combination of analytical techniques can detect all of the metabolites present in complex samples. Therefore, some groups define the approach as metabolic profiling. We will discuss this further, later in the course. Metabolites are low molecular weight biochemicals, including carbohydrates, amino acids, nucleotides, and lipids. They are the intermediates and products of metabolism. They are the building blocks for larger biochemicals, including DNA, RNA, and proteins.
Skip to 0 minutes and 49 secondsThey are involved in the structural components of cells and in the regulation of other biochemical processes, including the regulation of enzyme activity of proteins through allosteric and post-translational modifications. The entire qualitative collection of metabolites in the biological sample is called the metabolome. The human body contains many different metabolomes representing different biofluids and tissues. And each of these metabolomes is unique in which metabolites are present and the concentrations of each metabolite. The metabolome typically involves four classes of metabolites.
Skip to 1 minute and 29 secondsThose metabolites involved in endogenous metabolism, which can be separated into anabolic or catabolic metabolism; the metabolites taken up from the external environment through nutrients in a cell culture and drugs in the human population; those metabolites involved in exogenous metabolism, including the metabolism of drugs; and, finally, metabolites derived from symbiosis, for example, metabolites synthesised from the gut microflora in humans. Metabolism is the integration of the chemical and physical processes in which metabolites are broken down or synthesised. A single metabolic reaction converts one metabolite to another metabolite via an enzymatic reaction. Groups of metabolic reactions can be integrated into a metabolic pathway, and the complete set of metabolic reactions can be visualised as a metabolic network.
Skip to 2 minutes and 23 secondsThe networks are similar to a map of the London Underground where tube stations are metabolites and train lines and the metabolic reactions. To give an example, glucose is converted to glucose-6-phosphate by the enzyme hexokinase, which is then converted to fructose-6-phosphate by the enzyme phosphoglucose isomerase. Eight other reactions follow to lead onto the synthesis of pyruvate. These groups of reactions are described as the glycolysis pathway. Metabolomics is regarded as the younger sibling of the omics sciences, but the study of metabolites and metabolism has actually been performed for more than a hundred years. The metabolics field is strongly founded within biochemistry. That is the study of chemical processes within living organisms.
Skip to 3 minutes and 10 secondsMetabolites were first measured in the pioneering work of the early biochemists, including Sir Hans Krebs, who discovered the citric acid and urea cycles, and Eduard Buchner, who discovered that glucose was converted to carbon dioxide and ethanol by yeast juice. This "juice" is now known to have contained the collection of enzymes that we associate with the metabolic pathway, glycolysis. These discoveries occurred more than a hundred years ago. This pioneering work, investigating one or few metabolites at a time, helped re-construct many different metabolic pathways that were then integrated into metabolic networks. The term, metabolomics, was first used in 1998 by Professor Steve Oliver and colleagues.
Skip to 3 minutes and 54 secondsAnd, in the same year, the term metabonomics was defined by Professor Jeremy Nicholson at Imperial College London. The terms are often used interchangeably. However, the definitions are different. Metabolomics is a comprehensive study to quantify and identify all of the metabolites in a biological system while metabonomics is the quantitative measurement of the dynamic, multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification. A few years after the definition of these terms was proposed, a number of studies were published showing the application of metabolomics to study microbes, plants, and animals.
Skip to 4 minutes and 38 secondsThe metabolomics field has rapidly expanded over the past 15 years with more than 2,400 papers published in 2014, across a wide range of application areas across the life and medical sciences. The metabolomics field has rapidly develop due to improvements in analytical instruments, compute power, and software. Interdisciplinary groups of chemists, biologists, and computer scientists have all helped drive forward metabolomics to its widespread use today in diverse areas in academia, as well as the biotechnology and pharmaceutical industries. Metabolomics is applied in a wide range of biological and clinical applications. One example which I am interested in is stratified medicine.
Skip to 5 minutes and 23 secondsCurrently, it is assumed that we are all the same, and we are all at the same risk of developing a disease, and that we will all respond in the same way when prescribed a drug. However, we are all different. We develop different diseases and respond differently when given a drug. As metabolomics measures dynamics in the phenotype, it is a powerful tool to separate or stratify patients into different groups based on low or high risk of developing the disease or whether a patient will respond or not respond to a specific drug.
Skip to 5 minutes and 55 secondsPrescribing the correct drug to use first time, rather than assessing different drugs one at a time, will increase survival rates in diseases, including cancer, as well as say the healthcare services millions of pounds.
What is Metabolomics?
Dr Warwick Dunn provides an introduction to metabolomics, a definition of the commonly used terminology and an overview of the history and development of metabolomics.
© University of Birmingham and the Birmingham Metabolomics Training Centre