One of the greatest mysteries in biology is how biology itself began. How on your Earth, life's meta turned into living organisms. You probably heard of the Miller-Uri experiment, conducted by Stanley Miller and Herrert Uri. It was performed in 1952. It is seen as evidence that amino acids, organic molecules necessary for modern life, can emerge from inorganic compounds and conditions the early Earth provided. Therefore, hydrogen, methane, ammonia and water were used to simulate the atmosphere of the early Earth. Energy was delivered into the system by firing electrical sparks, imitating lightenings in the ancient Earth's atmosphere. After a reaction time of one week, five different amino acids have been produced. Three of them, glycine, alpha-alternine and aspartic acid are protein or genic. They are fundamental building blocks of proteins, biopalamus, without which life as we know it, wouldn't be possible. But a few amino acids aren't life, and since 1952, a lot of research has been done on this topic. Living organisms have a complex set of metabolic reactions, and one key question is how this metabolism developed. One very old metabolic pathway was found to be the acetal co-a pathway in the methanogens and acetylchons. Methhanogens are a key of producing methane as a product of the energy metabolism by reduction of CO2. Acetytotions, however, are a group of bacteria and archaea that produce acetate out of CO2. Both methanogens and acetytotions are anaerobic. They don't need oxygen, and both have the ability to use this acetal co-a pathway for carbon fixation. These are already the first arguments for the pathway's age. It appears in only distantly related organisms and has therefore evolved very early. It also appears exclusively in anaerobic organisms, since life emerged before the atmosphere contained much oxygen. Other hints for its age are that it has no stereochemically defined intermediates and does overall release energy. Via the acetal co-a pathway, microorganisms can generate acetate or acetal co-a after which it is named, methane and pyruvate through reduction of carbon dioxide. As a reducing agent, NADH and NADPH, reduced ferroduxin and F420 are used, but ultimately the environmentally available source of electrons is molecular hydrogen. These reactions are catalyzed by a total of 10 enzymes. You now may think, one moment, 10 highly specialized enzymes seem a bit complex for a pathway advertised to be this old. But it seems like this pathway could even be older than the enzymes it is catalyzed by, because all of these reactions can be performed with one rather simple mineral as a catalyst. This mineral is called a varuite and consists of metallic iron and nickel. The reaction needs alkaline hydrothermal conditions, like very frequently occur around submarine hydrothermal vents. And when we take a closer look on many of the enzymes of the acetal co-a pathway, we'll find that many of them contain iron, nickel or both of them, either for transition metal catalysis or in transition metal sulfide clusters. All of this is pretty good evidence that this particular pathway has been around longer than the enzymes catalyzing it, and has evolved from prebiotic reactions with only one simple inorganic catalyst. Recently, a paper on thermodynamics of early metabolic pathways was published, trying to answer the question which biosynthetic reactions evolved first, and which energy source fueled with ancient reactions. The authors used a set of reactions that are known to appear in both bacteria and archaea. The form of network and are responsible for the synthesis of basic cell constituents such as amino acids, nucleotides and cofactors. Because of their universal appearance, these reactions trace all the way back to Luca. Luca's name given to the last universal common ancestor of all living organisms, because biologists, like all other scientists, have a weakness for mediocre naming puns. Of course, this set of reactions also includes the acetal co-a pathway. I want to begin with just a few definitions. The second question is about the reaction that the reaction does happen spontaneously. More technically spoken, it is a reaction with negative change of Gibbs free energy. This Gibbs free energy, delta G, is a parameter used to describe a change of entropy in a closed system and its surroundings through a reversible reaction. A system tries to reach a minimal absolute value of Gibbs energy until it reaches an equilibrium with a delta G of 0 and no net change in concentrations of substrates and products. Required for a change in concentrations is a negative delta G. The investigated reactions build up cell mass out of hydrogen, carbon dioxide, hydrogen sulfide and phosphate. Gibbs energies of only individual reactions of the network were calculated. Modern organisms use redox reactions to acquire energy and store energy in the reactive phosphonhydride bond of ATP. Just a few of Luca's biosynthetic reactions use ATP hydrolysis to harness energy. The office therefore concentrated on exogonic ATP independent reactions. But there are some things that had to be considered. The Gibbs energy couldn't simply be calculated using standard conditions. The metabolic reactions happen under non-equilibrium conditions because products of one reaction can be used to substrates for other reactions, excreted out of the cell or used to build up proteins, sugars or nucleic acids, creating a steady state equilibrium. The substrates however are provided in constant amounts. Under equilibrium conditions 78% of the metabolic reactions are exogonic, but with 100 fault more substrate than product 98% of them are exogonic. This means that nearly all reactions of Luca's metabolism could sustain themselves. Maybe, unlike in the Miller-Uri experiment with a simulated lightning, no external energy source was needed and the energy came from Luca's metabolism itself. Something else that needed to be considered was that a variety of organic covectors we are used to today probably didn't exist back at the beginning of metabolism. So all biological reducing agents were replaced with molecular hydrogen. That wasn't done without president because there are even modern microbes using hydrogen as a reducing agent. In these organisms, reductions are usually carried out by reduced iron sulfide centers, which in turn get themselves reduced by hydrogen. Most of the reactions turned out to be exogonic at a pH of 9, 80 degrees Celsius and a low concentration of environmental hydrogen. These conditions are usually observed at submarine hydrothermal vents. This is the exact same environment, where modern methanogenic and the cytogenic organisms live and it's very likely that this kind of environment already existed on the early earth. Also, as we already discussed, hydrothermal vents are where substances like pyrovate, formate or acetate get generated geochemically with metacatalysts. Overall, the metabolic network of Luca provides its own energy without any other energy source when it substrates themselves. The energy comes from the exogonic reaction of hydrogen and carbon dioxide to pyrovate, energy-releasing reactions of carbon like reductions, the formation of rings and aromatic systems, alkyl transfers and so on. Only a 3% of Luca's metabolic reactions are endogonic. The total flow of energy goes from the highly energetic elemental hydrogen and low energy CO2 to reactive carbon compounds to more stable products. If you enjoyed the video, please consider giving it a like or subscribing to the channel. And if you want to discuss the topic further, leave a comment down below. Thanks for watching!