The Origin of Metabolism and GADV Hypothesis on the Origin of Life

Abstract

Metabolism is a network of chemical reactions that are catalyzed by enzymes encoded by the respective genes. Several ideas for explaining the origin of metabolism are proposed, assuming that the proto-metabolism should be a chemical reaction system, in which the reactions were carried out with minerals, such as pyrites or rocks on hydrothermal vents in a deep sea. In such cases, the activities on minerals must be converted at one time to protein enzymes. However, it would be impossible to transfer the catalytic activities in such a nonprotein reaction system to protein enzymes because of the three-dimensional structures of both catalysts. Therefore, four conditions must be satisfied to explore the origin of metabolism as follows: (1) Chemical reactions, even in the initial metabolism, must be catalyzed by proteins, which might be incomplete and immature because of the absence of genes at that time point. (2) Organic compounds, which were easily synthesized with prebiotic means and accumulated in large amounts on the primitive Earth, should be used as reactants in the metabolism. (3) In addition, organic compounds produced in the initial metabolism must be useful for the emergence of the first life. (4) Catalytic reactions with fewer reaction steps would be favorable for the initial metabolism. Therefore, catalytic reactions incorporated in the initial metabolic system must be driven by proteins, and useful organic compounds must be produced with organic compounds, which accumulated in large amounts on the primitive Earth. From analyses of metabolic reactions under the four conditions, it is concluded that the initial metabolism originated from three organic compounds— glyoxylate, pyruvate, and glyceraldehyde—which also play central roles in modern metabolic pathways. The former two organic compounds lead to syntheses of four [GADV]-amino acids (Gly [G], Ala [A], Asp [D], and Val [V]). The third organic compound is a precursor molecule for synthesis of ribose-1-phosphate, which is necessary to produce nucleotides and RNA. The [GADV]-amino acids could be produced from the precursor molecules in a smaller number of reaction steps than synthesis of the nucleotide, which requires ribose-1-phosphate and nucleobases as precursor molecules. Therefore, the origin of metabolism proposed in this chapter supports the idea that life emerged according not to the “gene/replicator first” theory, but to the “protein/metabolism first” theory on the origin of life. The idea, suggesting that life emerged from the [GADV]-protein world and not the RNA world, is also supported from the viewpoint of the origin of metabolism.