How my insane workout sparked my venture in metabolomics! 💪🏋️‍♂️

Ayaan Esmail
10 min readFeb 1, 2019

The other day I was at the gym, and you know I was doing the usual, easy workout of:

  • 400 lbs single-arm dumbbell bench press x 0 reps. (5 sets)
  • 710 lbs dumbbell flyes x 0 reps. (5 sets)
  • 1,000 lbs dumbbell pull-over x 0 reps. (8 sets)

And after that effortless workout, I got hungry, when I came out of the change room I could literally hear my belly grumble. Not only that, there was a McDonald’s nearby. So, just like any bodybuilder would do, I decided to eat super healthy and ordered the McDonald’s Angus burger, with large fries and a kid-sized diet coke. For some random reason, I felt much better! My dying hunger and belly grumble went away, and I felt 10 times more energized and ready to take on the day. Now, maybe this was because of my insanely amazing workout or the very healthy food that I ate, but bottom line is - I felt hungry, ate food and felt energized.

But why did that happen? How did my energy levels just shoot up right after eating food? I got super curious and figured that it was because of my metabolomics.

So you might be thinking “what is metabolomics?!” that’s what I thought at first too. So I researched even deeper, reached out to a few people in the field, and to be honest it’s what’s been occupying my time these past few months.

No not exams, not the number of likes or followers I have, my knowledge base in metabolomics is what’s been occupying most of my time. And so I thought, hmmm, why not write an article about what I learned/am learning, and here you are reading that very article that I was thinking about.

Oh, and if I blow your mind don’t blame it on me, blame it on the insane potential of metabolomics, seriously this technology is amazing.

In this article, I’ll be exploring how this new field dictates everything we do on a daily basis, including generating energy for our bodies. But overall. How we can use it to discover biomarkers, prevent cancer, and personalize medicine.

An introduction to the world of metabolomics

Metabolomics is the large-scale study of the metabolites within cells, biofluids, tissues or organisms. Metabolites are small molecules that help with interactions in the body and are continuously being absorbed, synthesized, degraded and are always in contact with other molecules both within and between biological systems, as well as with the environment.

The different metabolite functions.

While sleeping, eating, working or engaging in anything, you need energy. Energy is supplied from your diet in the form of calories and then broken down and used in your cells, tissue, etc. So those burger and fries did come in handy 😉.

If it wasn’t for our metabolites, we wouldn’t be able to break down the foods we eat into energy to interact with our environment and stay healthy.

But let’s dive a little deeper into this, energy generation definitely isn’t something simple. It requires a bit more knowledge about metabolites.

Just to give you a general sense of how important metabolites are - not only us but most of the structures that make up animals, plants and other living organisms also use metabolites, and they’re all made from three basic classes of them: amino acids, carbohydrates, and lipids. All metabolic reactions focus on making or breaking these molecules. They can then be joined together to make DNA and proteins, essential macro molecules of life.

But then again, how does this all contribute to generating energy and me feeling better after my amazing workout? Well, that’s where our metabolome plays a role. You can think of it like this - the metabolome is the commander and the metabolites are its army. Understanding its armies capabilities, the metabolome basically tells the metabolites what to do to maximize the outcome, and instead of giving them really complex tactics and strategies, it gives them 2 commands, either:

a.) Help build energy via catabolism.

Or

b.) Help build energy via anabolism.

When the metabolome tells the metabolites to help build energy via catabolism, it’s basically asking them to break down complex molecules to release energy. Whereas with anabolism, it tells the metabolites to do the opposite, generate complex molecules using energy and simple molecules. Both of these types of metabolic activity are interconnected through metabolic pathways, which I’ll talk more about later on.

Each metabolomic reaction that occurs (including catabolism and anabolism) is organized into metabolic pathways. In this process, one chemical is transformed into another through a series of steps, each facilitated by enzymes. Enzymes are crucial in metabolism because they allow organisms to get to their end goal by providing them with energy. In most living organisms the process of energy generation also needs a little bit of energy to start with. These enzymes are also catalysts, which means that they help to speed up the reactions as well.

How we can use metabolites to generate energy

There are two main types of metabolic pathways: catabolic and anabolic.

Catabolic pathways break down large molecules into smaller units. The cells use the monomers released from breaking down polymers, to degrade the monomers into simple waste products, which end up releasing energy. The creation of these wastes is usually an oxidation process which releases free energy, some of which is heat, but the rest of which is used to drive the synthesis of ATP.

ATP is the gateway to energy. This molecule acts as a gate for the cell to transfer the energy released by catabolism to the energy-requiring reactions that make up anabolism. Overall the catabolic processes provide the chemical energy necessary for the maintenance and growth of cells, which ties right into anabolism.

Anabolic pathways work to synthesize complex molecules by using the energy released by catabolism. These complex molecules are then used to form cellular structures that act as building blocks in our body. These processes are powered by the cleavage of ATP.

If there’s one thing important, it’s that the cleavage of ATP is what powers the process of anabolism, this is done through something called ATP hydrolysis.

The chemical structure of ATP - our bodies currency of energy.

During anabolism, we need to do the cleavage of ATP. This can be done through ATP hydrolysis and is how cells break down ATP to use its energy, and the way it works is right in the word itself. Hydro is Greek for“water” and lysis is Greek for “to split”. In ATP hydrolysis we use water to break apart ATP to convert it into adenosine diphosphate (ADP).

Our inputs and outputs for ATP hydrolysis.

There are 4 steps to ATP hydrolysis:

1.) ATP is produced through catabolism, it then starts to hydrolyze, which means that it starts to be broken down into its individual amino acids by water. The first water molecule will willingly give one of its extra pairs of electrons to the hydrogen and eventually, it will end up stealing this hydrogen molecule forming a hydronium ion. This, in turn, causes the second water molecule into an unstable hydroxyl group.

2.) As a result of making the hydronium ion, the oxygen in the second water molecule now has a third lone-pair of electrons. It donates this third lone pair to the oxygen of the robbed molecule and the robbed molecule becomes an unstable hydroxyl group, that will make it work even harder to get other electrons to create a full octet.

3.) Because of the instability of the hydroxyl group, it decides to form a bond with the phosphorus of the first phosphate group in the ATP molecule.

4.) The phosphate group that made a bond with the hydroxyl group, is now called a phosphoryl group. It breaks off from the ATP molecule and the electrons that formed the bond that attached that phosphate group to ATP, move onto the neighboring oxygen.

These actions cause the oxygen molecule to become negatively charged, produce ADP, and produce energy. The bonds of the phosphate group contained high energy electrons. When the phosphate is broken off, the high energy electrons come down to a lower energy state.

When an electron jumps from one state level to another, it releases energy. This energy is then used to help repair tissues, cells and help the body interact with the biological system within itself and in the environment around it!

A sort of accurate visualization of the 3rd and 4th step. (Watch till the end)

Applications of metabolomics

We talked about why we need metabolomics, but what else can we use it for other than keeping ourselves alive. Well, it can also help us understand the body better, provide personalized medicine, exponentially improve the agricultural industry, and diagnose cancer!

Metabolomics can be used to understand the body better through the analysis of biomarkers. Biomarkers are observations of a patient’s medical condition from the outside that can be measured accurately and reproducibly. In metabolomics, the biomarkers we analyze are the individual metabolites. We usually split these up into two groups; a control group, and a disease group. For example, a metabolite that is present in disease samples, but not in healthy samples would be classed as a biomarker. Urine, saliva, bile, or seminal fluid contain highly informative metabolites, which is why when you go to the doctor, they will ask you to pee into a bottle.

Also, since we know that metabolites control what the DNA will code for, if we can understand what metabolites will help in the construction of nucleotides, we can see what the DNA will code for before its even made! Basically, we can see reactions that might occur in the body months or years, before they even occur.

Example, if we can see what metabolites are forming to code for certain DNA that might allow cancer cells to form, we can take steps towards preventing it from now, so that it doesn’t even occur in the first place. Below is a diagram which shows how we do metabolic profiling via two approaches, untargeted and targeted:

We can also use metabolites to provide personalized medications. If we can see how a medication might react with the patient by simulating the metabolic reactions, we can personalize medications towards specific patients metabolite groups.

Right now we give everyone the same medication, but we don’t take into consideration that we all have different compositions of metabolites. Meaning the medication will react differently for different people. If we are able to categorize medications based on a patient’s metabolites, we will be able to create medication that is more precise and effective. So yes, you can throw out all your medications since they’re not effective and not personalized. Just kidding.

Metabolomics can also revolutionize the agricultural industry. In short - we can improve the understanding of metabolic networks and the biochemical composition of plants and other biological organisms related to agriculture. Analytical tools in metabolomics including mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (NMR), can tell us the impact of time, stress, nutritional status, and environment on hundreds of metabolites simultaneously, which just gives us loads of data that we can then use to decode the composition of an organism. This information, in combination with transcriptomics and proteomics, has the potential to generate a more complete picture of the of the food we eat, help optimize crop development, help us know certain functions of organisms we did not know before, simulate how certain pesticides or products in the environment surrounding them could help or degrade plant growth, and enhance diet and health.

I want you to imagine a world where cancer is a prevalent problem, and that hundreds of people die due to it every day. Sadly, that’s the world we live in today. Yea I know, it sucks. We still haven’t found a cure for this deadly disease and one of the reasons why is because we haven’t cracked a way to detect it.

Right now our approach to curing cancer is reactive, but what if we made it proactive, and eliminated the disease before it occurs. This is the mindset behind cancer metabolic scientist and researchers from Qatar, Georgetown, and California University. They have actually teamed up to create a metabolic test that will allow early detection of pancreatic cancer (PC).

In their study, they attempted to externally replicate metabolite biomarkers of PC reported by several other groups. They used mass spectrometry to detect these metabolite markers and identified a biomarker panel that differentiates between normal patients and PC patients, with high accuracy. So basically detecting cancer-based on your metabolites to help diagnose you way in advance!

Key Takeaways

Now that was probably a lot to take in, so just like your grandma bakes you cookies in the kitchen, I whipped up some key takeaways for you 😉.

  1. Metabolism is the key to life and is the study of small metabolites within cells, biofluids, tissues, or organisms, without it our bodies would not be able to produce heat and energy which are literally the most important molecules we need to stay alive.
  2. Energy is produced through a process called ATP hydrolysis in which we break off a phosphate group from ATP to form ADP. We do this by adding water into the equation, hence the name hydrolysis.
  3. There are two types of metabolic pathways that we use to generate heat and energy: anabolic pathways, which generate complex molecules from simple ones with the help of energy, and catabolic pathways break down complex compounds and molecules to release energy.
  4. Metabolomics has immense potential and we can use it to help gain a better understanding of humans, provide personalized medicine, exponentially improve the agricultural industry, and detect cancer!

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