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The reductive citric acid cycle is incapable of self-organization



Professor Orgel has given a detailed critique (Orgel L. Proceedings of the National Academy of Sciences USA, 2000, 97, 12503-12507) of the theories of Professors Wächtershäuser and Morowitz. Professor Wächtershäuser has put forward the theory that the reductive citric acid cycle and other organized chemistry took place on the surface of  iron sulfide minerals. But the reductive citric acid cycle is a complex cycle involving a family of disparate reactions, and there is no evidence that a family of disparate reactions self-organizes on the surface of iron sulfide or any other mineral. There is no evidence that a particular mineral catalyzes a family of disparate reactions. A suite of minerals has also been proposed, but: “Any suite of minerals that included catalysts for each step of the cycle would be likely to include, in addition, catalysts for reactions that disrupt the cycle. Efficient transport of the intermediates from one catalytic mineral to another would also present severe problems” (Orgel L. Proceedings of the National Academy of Sciences USA, 2000, 97, 12503-12507).

This critique by Professor Orgel was written three years ago. In the last three years Professor Wächtershäuser has published several papers on various aspects of prebiotic chemistry but, as far as I could determine, he has not addressed Orgel’s critique. This suggests that Wächtershäuser admits that his theory lacks experimental support. I wrote to Wächtershäuser recently about this, but I have not yet received a reply.

Professor Morowitz has proposed that the entries in Beilstein’s Handbook of Organic Chemistry  support the theory that the reductive citric acid cycle did in fact self-organize. The Beilstein handbook is a  database of millions of organic compounds studied in detail by chemists. Morowitz is impressed by his discovery of a set of pruning rules that reduce these millions of entries to only 153 compounds, which happen to include all of the citric acid cycle intermediates. But these pruning rules are formulated to include these intermediates and exclude many of the other molecules listed in the Beilstein handbook: “Compounds are included only if they contain no more than six carbon atoms, contain only carbon, hydrogen, and oxygen in certain composition ranges, include a ‘carbonyl’ group, etc. Equally plausible rules that would occur to an organic chemist seem not to have been considered. Many would either exclude citric acid cycle intermediates or permit the inclusion of a much wider range of other compounds. Why restrict the number of carbon atoms to six rather than five or seven? The choice of five would have led to the exclusion of many of the citric acid intermediates, whereas the choice of seven would have led to the inclusion of a large number of unrelated compounds. …We see, therefore, that all of the citric acid cycle intermediates appear in Beilstein because they are important biochemicals and of interest to organic chemists, and that they are not excluded by the pruning rules because the pruning rules are formulated in a way that allows their inclusion” (Orgel L. Proceedings of the National Academy of Sciences USA, 2000, 97, 12503-12507).

Evolution requires more than just self-replication. Evolution requires self-replication with mutations to generate variation. Without variation, all of the copies are identical with the original, and hence there is no possibility of evolution. Could proteins have achieved the power of self-replication with mutations? Although proteins have been described that catalyze the ligation (binding together) of two peptides (short proteins) to form copies of themselves (Paul N, Joyce G. Proceedings of the National Academy of Sciences USA, 2002, 99, 12733–12740),  evolution can not occur because the copies are identical with the original. Some of these proteins catalyze the ligation of peptides with different amino-acid sequences, thereby forming new proteins. What would have been the fate of these proteins? Unless proteins and nucleic acids are regularly replicated, they decompose under the conditions existing four billion years ago (Joyce, G. Nature, 2002, 418, 214–221). Replication of the particular sequence of amino acids in a protein requires a team of sophisticated molecules that did not exist four billion years ago (Page 1319 of Johnston W, Unrau P, Lawrence M, Glasner M, Bartel D. Science, 2001, 292, 1319–1325). No one has demonstrated a collection of proteins arising under the conditions existing four billion years ago that does anything other than decompose. Thus, unaided proteins could not have achieved the power of self-replication with mutations.



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SUBTITLES

Introduction
The RNA Dream World a), b)
Nucleic Acids are Incapable of Self-replication
The Reductive Citric Acid Cycle is Incapable of Self-organization
A System Composed of Nothing Other Than Proteins is Incapable of Evolution