Our cells are constantly orchestrating a complicated dance of atoms and molecules inside our bodies, using energy to manufacture, distribute, and deploy the chemicals on which our lives rely.
And it’s not just in human bodies: all creatures perform this metabolic dance, and it turns out that none of them do it exactly the same way.
In a new study published in Science Advances, we examined individual carbon atoms in amino acids, the building blocks of proteins, to identify distinct fingerprints of each species’ metabolism.
These fingerprints explain how various animals manage the demands of survival, development, and reproduction – and provide an entirely new method to comprehend metabolism in unparalleled depth.
We’ve created a new approach for studying metabolism – the chemical processes inside your body that keep you alive and functioning – that yields far more information than prior methods. Our novel method examines isotopes inside amino acids to determine how metabolism works.
Isotopes are distinct mass variants of the same chemical element. For example, carbon-12 is the most common type of carbon, but there is also a heavier isotope called carbon-13. We can learn about the creatures that produced biological compounds like proteins by measuring the ratio of heavy to light isotopes.
Traditionally, scientists would examine the protein’s total isotope ratio. This can give some information, particularly about what an animal consumes, but it’s like averaging out a complicated TV image into a single pixel of light – you lose all the complexity.
Scientists have lately been able to quantify isotopes in each of the 20 different amino acids that comprise proteins. This is equivalent to having 20 dots of light – better, but still lacking in nuance.
Our new technology goes even further, measuring isotopes in each amino acid’s carbon atom. It’s like viewing every pixel in a TV display, and it provides us with incredibly specific metabolic data.
Finding the right carbon: We utilized a chemical called ninhydrin to remove and isolate the desired carbon atom from each amino acid. We next ran these carbon atoms, which came from a particularly metabolically active component of the amino acid called the carboxyl group, through a mass spectrometer to determine their isotopic fingerprints.
This study began more than a decade ago and has since evolved into a collaboration between Griffith University and Queensland Health. Working with colleagues in Japan, we demonstrated in 2018 that we could actually use nihydrin to separate the carbon atoms we want from amino acids.
The next step was to combine our nihydrin approach with a method known as high-performance liquid chromatography, which can separate different types of amino acids.
We were able to publish position-specific isotope analyses for numerous mammals in 2019. We discovered a distinct metabolic “fingerprint” for each species.
The four phases of metabolism: In our most recent study, we evaluated a wider variety of creatures, including oysters, scallops, prawns, squid, and fish. We discovered that isotope patterns in amino acids could be traced back to the biology of mitochondria, the tiny energy-producing powerhouses found in the cells of all animals, plants, and many other creatures.
We discovered four unique phases of metabolism: fat creation, fat destruction, protein creation, and protein destruction. Animals combine these stages in various ways to achieve growth and reproduction.
Adult mammals, for example, use fats as a storehouse to regulate their body temperature, but adult prawns cannibalize their own proteins to produce the fats required for reproduction.
We also discovered that the humans we tested had a relatively balanced, steady-state metabolism, which may come as no surprise given our generally consistent and nutritious diets. Surprisingly, this was very similar to what we discovered in an oyster sample.
In this study, we looked at people who had generally normal metabolisms. Future uses could involve research into metabolic disorders such as cancer, obesity, and hunger.
We will be able to study eukaryote metabolism in animals, plants, and fungi like never before by gazing deep into amino acid isotopes.
