The Implausibility of Metabolic Cycles on the Prebiotic Earth

0005 C ycles occur widely in all branches of chemistry. The definition of a catalyst as an agent that facilitates the conversion of reactants to products without itself being changed almost guarantees that a catalyst can initiate successive " cycles " of the same reaction. Metabolic cycles are different. Strictly, they are by definition restricted to biochemistry. Like catalytic cycles, they too result in repeated conversions of substrates into products, but they involve much more complex sequences of chemical reactions. As far as I am aware, the formose reaction, which converts formaldehyde to a complicated mixture of products, including various sugars [1], is the only known nonenzymatic reaction sequence that is at all similar to a metabolic cycle, although the existence of one or two much simpler cycles has been established or made probable in the literature of prebiotic chemistry [2,3]. The possibility that reactions of hydrogen cyanide (HCN) might form the basis for a complex cyclic organization has been proposed [4], but there is as yet no experimental evidence to support this proposal. If complex cycles analogous to metabolic cycles could have operated on the primitive Earth, before the appearance of enzymes or other informational polymers, many of the obstacles to the construction of a plausible scenario for the origin of life would disappear. If, for example, a complex system of nonenzymatic cycles could have made nucleotides available for RNA synthesis, many of the problems of prebiotic chemistry would become irrelevant. Perhaps a simpler polymer preceded RNA as the genetic material—for example, a polymer based on a glycerol-phosphate backbone [5] or a phosphoglyceric acid backbone. Could a nonenzymatic " metabolic cycle " have made such compounds available in sufficient purity to facilitate the appearance of a replicating informational polymer? It must be recognized that assessment of the feasibility of any particular proposed prebiotic cycle must depend on arguments about chemical plausibility, rather than on a decision about logical possibility. Any reaction sequence that is allowed by thermodynamics could, in principle, be realized, given a sufficiently active and specific family of catalysts. Plants synthesize complex alkaloids, such as strychnine, from CO 2 , NH 3 , and reducing equivalents, so it must, in principle, be possible to achieve these syntheses starting from CO 2 , NH 3 , and H 2 , given a family of sufficiently active and specific prebiotic catalysts. However, few would believe that any assembly of …