The Omics, Metabolome and Other Reasons Why Being A Health Nut Is Going To Become Overrated
“The genomics revolution, proteomics and metabolomics, all of these ‘omics’ sound so terrific on grants and on business plans. But, what we are doing is we are seizing control of our evolutionary future. I mean, we’re essentially using technology to jam evolution into fast-forward.”
Says Gregory Stock, a biophysicist and former director of UCLA’s Medicine, Technology and Society program (a program dedicated to researching metabolomics and genomics).
Let’s be honest with each other here:
Gummy bears > Vegetables 🍭
Yes, you can argue that vegetables have more nutrients, but let me propose this; what if we could identify the nutrients your body lacks and push specific amounts of those nutrients. My parents tried to feed me vegetables, whether through raw vegetables, stews or juices. It either ended up on the wall, never eaten or fed to the garbage can. This would be a massive help to both vegetable-haters and agriculture, diseases with no identifiable biomarkers and the field of personalized medicine.
But, we already have so many other ‘omics.’
The puzzle never fit, a piece has always been missing, and that piece is Metabolomics. Since completing the Human Genome Project in 2003, we’ve entered a new post-genomic era of biology. So we now have the blueprint of life composed of DNA called the genome.
But this genetic code will not answer all the questions that we have about human disease and environmental health. Instead, we need to measure the combined effect of the genome, lifestyle, and environment on how we function. This results in what we call the phenotype. So metabolomics provides a direct and sensitive measure of the phenotype at the molecular level.
This sounds great and all, but to know if this is effective, we need a clear definition of precisely what the metabolism is?
Light the Campfire ⛺️
Let’s start a campfire (aka your metabolism)! You’ve got to put the right amount of wood in the proper increments to get a large campfire. If you’re not putting enough wood on or going too long without throwing any wood on the flames, it’s going to die. If you put too much on it at the same time, the fire might be smothered.
The sciencey word for metabolism today has come to have a distinct meaning in popular speech, but metabolism isn’t a singular entity.
People speak about metabolism as primarily how fast your body burns the fuel in your food or how high your personal energy state is. That’s fine to be used by personal trainers and fitness magazines. But physiologically speaking, the term metabolism describes every single biochemical reaction that goes on in your body. More importantly, it reconciles two conflicting chemical processes that are always concurrently underway inside you.
- Anabolism is one of those chemical powers. Anabolic reactions create stuff and absorb energy. These are the processes that take the small monomer building blocks in your food — like monosaccharides and fatty and amino acids — and build them into larger, more complex polymers such as carbs and fats and proteins.
- Then, when you need new building blocks, or when you need some fuel, those polymers in your body, or ones in your food, get broken up by catabolic reactions. Catabolism processes break down larger molecules, and when they break their bonds, release the energy you need to stay warm, move about, and provide fuel to your cells… to build up the polymers again.
Your metabolism is a lot like Sisyphus. It’s always working diligently. But it’s never finished. And the boulder that your inner Sisyphus is still pushing up and making you slide back down? Those are all nutrients — the molecules that your body is forever breaking apart and then repairing, only to break them apart again.
Breaking Down The “Break Down Machine”: 🤖
Metabolomics is a non-biased experimental approach that aims to measure all of the metabolites in the biological sample. Although the approach is designed to be unbiased, no single analytical technique or even a combination of analytical methods can identify all of the metabolites present in complex samples. (Which happen to be quite literally, all of them). Thus, some groups define the approach to identifying biomarkers as metabolomic profiling. In other words, the field requires a way to identify metabolites, even in cases where the sample might seem too complicated.
Let’s take a step back; what even are metabolites?
Metabolites are low molecular weight biochemicals, including carbohydrates, amino acids, nucleotides, and lipids. They are the intermediates and products of metabolism. Think of metabolites as a dinosaur fossil. Through metabolites, we get to understand what exactly happened visually.
Some roles of metabolites include:
- Building blocks for larger biochemicals, including DNA, RNA, and proteins.
- Involvement in the structural components of cells and the regulation of other biochemical processes.
- Regulation of enzyme activity of proteins.
The entire collection of metabolites in the biological sample is called the metabolome. The human body contains many different metabolomes, each represents different biofluids and tissues. Each of these metabolomes have different concentrations of metabolites present. Most commonly, the metabolome involves four classes of metabolites.
- Those involved in the endogenous metabolism, which can be separated into anabolic or catabolic metabolism.
- The metabolites taken up from the external environment through nutrients in a cell’s culture and drugs in the human population.
- Those metabolites involved in exogenous metabolism, including the metabolism of drugs.
- Metabolites derived from symbiosis, for example, metabolites synthesized from the gut microflora in humans.
Metabolomics Is A Network 🚌
Metabolomics is the integration of the chemical and physical processes in which metabolites are broken down or synthesized. A single metabolic reaction converts one metabolite to another metabolite via a reaction. Groups of metabolic reactions can be integrated into a metabolic pathway, and the complete set of metabolic reactions can be seen as a sort of network.
The networks are similar to a map of the BC Transit Map, where bus lines 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 to the synthesis of pyruvate. These groups of reactions are described as the glycolysis pathway.
Timeline of the ‘Omics’ 📖
Metabolomics is usually referred to as the younger sibling of the ‘omics’ sciences. Still, the study of metabolites and metabolism has actually been performed for more than a hundred years. The field of metabolomics is founded on biochemistry, the study of chemical processes with living organisms.
Metabolites were first measured in the pioneering work of the early biochemists, including Sir Hans Krebs.
The expression, metabolomics, was first used in 1998 by Professor Steve Oliver and his colleagues. Over the last 15 years, the area of metabolomics has grown exponentially, with more than 2,400 papers released in 2014, covering a wide variety of fields of application spanning life sciences and medical sciences.
Little Things, Big Image 🖼
A biological system is constructed with biochemical components, including metabolites and genes, and the interactions between components control the biological function or phenotype. For example, metabolism is the interaction of metabolites and enzymes (a set of proteins).
The impact of these interactions on biological function and the phenotype will vary; a small number of interactions may have the same or a more significant effect on the phenotype than a large or global set of interactions between the functional levels. These concepts demonstrate that we must study the system as a whole to understand the whole system.
Picture a Jigsaw puzzle:
A jigsaw puzzle image with (i) pieces not connected, (ii) enough pieces connected to identify most components in the picture and (iii) the complete picture showing all components.
We can’t see the entire picture until the jigsaw pieces are connected. Simply put, the components are essential, but the way the components communicate is more important. Yes, metabolomics is the study of unbelievably small artifacts, but we have to see the holistic portrayal before we dive in.
Gains and Losses: Nuclear Magnetic Resonance (NMR)
No, this isn’t a rocket (I thought the same thing). It’s a way to study metabolites. And although it’s ginormous and unconventional for the study of minuscule particles, it is one of the most popular and widely used technologies.
NMR is well suited to metabolic studies as it can uniquely classify and concurrently measure a wide variety of organic compounds. Unlike Mass Spectrometry (MS), the NMR is non-destructive, so samples can continue to be studied further.
The sample preparation for NMR is easy and mostly automated. However, the study of the NMR spectra of complex mixtures has historically been difficult. NMR has been commonly used for metabolite fingerprinting and profiling. The major drawback of NMR for detailed metabolite sampling is its relatively low sensitivity, rendering it unsuitable for studying many low-abundance metabolites.
- Rapid analysis.
- Low sensitivity.
- Limited use of libraries.
The field of metabolomics has grown rapidly due to advances in analytical methods, computing power and software. Interdisciplinary classes of chemists, biologists and computer scientists have all contributed to the development of metabolomics to its widespread usage in academia and the biotechnology and pharmaceutical industries.
Need an example, time to be mind blown by Metabolon! 🍕
Metabolon deciphers thousands of discrete chemical signals from genetic and non-genetic factors to reveal biological pathways.
“We make connections other ‘omics’ cannot, and provide the definitive representation of the phenotype.” (#metabolomicsissuprerior)
Metabolon is a company that uses metabolic drugs to help you deliver personalized treatments. Metabolon does this by knowing what chemical reactions will happen within your body when a drug is used to give you the right drug to improve your body’s metabolism.
The company allows students, researchers and experts to analyze their data and contribute to the studies through various forms. Metabolon is a research company that uses metabolomics to grave a path to future uses while also accounting for internal and external factors like health, disease, nutrition, microbiome, medication, pollution and more.
Why Give Up Being A Health Nut 🌰
Where are we to go now?
New techniques, such as metabolite imaging, and improved analytical technologies are making metabolomics increasingly useful for a broader range of biomedical and pharmaceutical applications. It has already entered the modern world. We now know that it can answer a wide-spanning set of questions regarding modern science and provide a glimpse of how tomorrow’s world and humans might articulate.
Energy, the source of life, has been studied for an extensive period of time now. Although we’d like to say that we genuinely understood biology’s connection to the phenotype before metabolomics, we never did. The Jigsaw Puzzle never was complete. We never lost the piece. It was always there, just never truly applied. The last part of the puzzle, the study of metabolomics, has only recently started. It’s a journey, and there’s so much more of the trail yet to be paved.
- Metabolomics is the large-scale study of small molecules (metabolites) within cells, tissues or organisms.
- The applications of metabolomics are found within the pharmaceutical, healthcare, and agriculture industries, among others.
- Two of the most commonly used analytical methods in metabolomic studies are Nuclear magnetic resonance (NMR) and mass spectrometry (MS).
- Metabolon is a company currently applying metabolomics to the identification of biomarkers and drug analysis + identification.
- Additionally, Metabolon allows customers to contribute to driving metabolomics research.
- Memorize ½ of the Krebs Cycle. (I’m currently working on this one!)
- Reach out to Metabolon and try out a project.
- Read this research paper’s abstract!