An article by Leslie Orgel (2008) entitled “The Implausibility of Metabolic Cycles on the Prebiotic Earth” investigates whether biochemical pathways could have occurred in simplified ways without the catalysing function of complex enzymes. Could autocatalytic cycles have occurred in protocells on the primitive Earth?
Biochemical research on reactions has shown that although mineral catalysts can catalyse biochemical pathways, they are not specific enough to avoid disruptive side reactions. (Side reactions produce the wrong product). Orgel writes,
“While enzymes discriminate readily between very similar substrates, such discrimination is rare, but not impossible, in reactions catalyzed by small molecules or mineral surfaces.” (Orgel 2008, page 4 of 10)
“Lack of specificity rather than inadequate efficiency may be the predominant barrier to the existence of complex autocatalytic cycles of almost any kind.” (Orgel 2008, page 5 of 10)
Experimental evidence shows that a very important aspect of enzymes in the building of the organic molecules of life is their ability to discriminate between very similar substrates. The highly specific catalytic activity of enzymes is due to their stable three-dimensional structure. This ensures that only the correct ligations are made in the joining of peptide monomers.
Orgel gives an analysis of a paper presented by Kauffman entitled “Autocatalytic Sets of Proteins”. Kauffman presents a theory of peptide self-organization in which he assumes that a mixture of monomer (short) peptides will condense spontaneously into a mixture of long peptides. Orgel shows that Kauffman has misunderstood the initial conditions that would give any chance of this happening.
Orgel, who has dedicated much of his life to investigating how cells and biochemistry could have originated by natural means, concludes that molecular evolution involving prebiotic amino acids and hypothetical complex nonenzymatic metabolic cycles must show chemical plausibility. He states that one autocatalytic cycle – the core of the formose reaction is understood reasonably well, and one or two other simple cycles may exist. However, three decades after Orgel’s original work his tone seems generally pessimistic; he ends the article with the comment,
“However, solutions offered by supporters of geneticist or metabolist scenarios that are dependent on “if pigs could fly” hypothetical chemistry are unlikely to help.” (Orgel 2008, page 9 of 10).
The conclusion that we may draw is that a natural origin to biochemistry has not been found despite large amounts of effort and imagination.
 Kauffman, S. A. (1986) Journal of Theoretical Biology Vol. 119, pages 1-24.