Metabolism is a key process in living things that enables fuel to be turned into energy, but its evolutionary origin is a long-standing enigma.
Now, a study by US researchers has found a simple reaction between two chemicals, called glyoxylate and pyruvate, in Earth’s primordial soup billions of years ago may have led to the first form of metabolism as we know it.
Today, most living things use a process called the Krebs cycle – a convoluted eight-step process which turns glucose into cellular energy – to metabolise food.
It is a highly complex and delicate process which is closely controlled by various enzymes.
However, the team of scientists found that when glyoxylate and pyruvate simply react in water, they make all the chemicals needed for a version of the Krebs cycle.
Researchers say it is possible these two innocuous chemicals may therefore have driven a primitive, inefficient and uncontrolled version of the Krebs cycle.
As a result, emerging life on Earth may have been able to utilise this process and start creating energy.
A study by US researchers has found a simple reaction between two chemicals, called glyoxylate and pyruvate, in Earth’s primordial soup billions of years ago may have led to the first form of metabolism as we know it (stock)
Glucose from food is broken down in a cell and its derivative, pyruvate, is the key chemical which starts the Krebs cycle. This eight-step process is what gives the mitochondria organelle the nickname ‘powerhouse of the cell’. Researchers now understand how it works, but have no idea how it evolved in the first place
Previous research into this conundrum tried to find metals which would act as primitive replacements for each enzyme that controls a stage of the cycle.
However, finding eight such metallic catalysts proved impossible, and research ground to a halt.
Professor Greg Springsteen at Furman University and Dr Ramanarayanan Krishnamurthy at the Scripps Research Institute were part of a team which took a different approach.
Instead of looking for what researchers thought should be there, the new study, published in the journal Nature Chemistry, looks at what they already knew was present.
‘Basically, we looked at what small molecules would have been available and what would be their chemistry,’ Dr Krishnamurthy told Quanta Magazine.
They settled on glyoxylate and pyruvate as ideal test subjects, and put them in warm water in a beaker to replicate how they would have mixed in Earth’s primitive stages.
What they found was astonishing, as the reaction produced myriad chemicals including various analogues for the ones seen today in the Krebs cycle.
The simple experiment and its results astounded the authors of the paper, with Dr Krishnamurthy calling it ’embarrassingly easy’.
Normally, chemical reactions are finickety, temperamental and hard to master, requiring constant surveillance and precise procedures.
However, this reaction was so simple, it could be done by a school child.
Academics from the US believe two chemicals, called glyoxylate (right) and pyruvate (left), may have been the chemicals to create the first ever version of the Krebs cycle. When they react together in warm water, as they would have done ion a primitibe Earth, they form various chemicals, including analogues to chemicals found in the Krebs cycle. Grey= carbon, red = oxygen, blue = hydrogen
Professor Springsteen said: ‘All you really needed to do to get the pathway started was [to] drop two stable reactants into buffered water and stick it on a warm hotplate.’
The research did not decipher the entire cycle, mechanism or route, instead revealing how the raw materials for a primitive Krebs cycle can be produced.
These two chemicals may have laid the foundations for the emergence of what we would come to know as the Krebs cycle.
In their study, the researchers say the emerging sequence could have led to ‘the advent of increasingly sophisticated pathways operating under catalytic control’.
Next, the researchers want to learn more about how the intermediary compounds form, interact and fit into the wider picture of metabolism as a whole.
The origin of metabolism, a critical process which must be understood in order to learn how life first evolved, is the holy grail for many biochemists.
It is just as important as knowing how DNA and RNA came to exist and form the genetic code interwoven into every living thing.
WHAT IS THE KREBS CYCLE?
Pictured, Hans Krebs, the man who won the Nobel prize for medicine in 1953
The Krebs cycle process got its name from the man who discovered it, Hans Adolf Krebs.
As a German man who was the son of a Jewish doctor, he fled Nazi German in 1933 to avoid persecution and spent his life understanding metabolism.
In 1937 he discovered a cycle that went on within cells, and in 1953 was awarded the Nobel Prize in Physiology or Medicine for his work.
It is an eight-step process which relies on eight different enzymes to force reactions to occur rapidly.
As well as the eponymous moniker, it is also known as the citric acid cycle or the tricarboxylic acid (TCA) cycle, based on two of its key components.
It occurs in the matrix of cellular mitochondria, a large organelle. The mitochondria are known as the ‘powerhouse of the cell’ and this process is why as it creates energy from fuel.
It begins with a chemical called pyruvate which is a simple is effectively half a glucose molecule. Glucose is a sugar regularly found in food.
Pyruvate is oxidised and turned into a chemical called acetyl co-enzyme A (acetyl CoA).
Pyruvate is also the chemical which is used in anaerobic respiration, leading to the inefficient production of energy and creating lactic acid during strenuous exercise.
It then reacts with a chemical called oxaloacetate, a compound with four carbons, to form citrate.
This is the first metaphorical domino to fall and triggers a series of reactions, each releasing energy from the bonds attaching atoms together.
This goes into molecules such as ATP (adenoside triphosphate) which is the universal energy currency of cells.
The cycle is regulated by eight enzymes which control each and every step, ensuring not too much or too little energy is produced at any one time.
The Krebs cycle (pictured, its individual stages in detail) is an eight-step process which relies on eight different enzymes to force reactions to occur rapidly