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The implausibility of metabolic cycles on the prebiotic Earth.

Orgel LE - PLoS Biol. (2008)

View Article: PubMed Central - PubMed

Affiliation: The Salk Institute for BiologicalStudies, San Diego, California, United States ofAmerica. gjoyce@scripps.edu

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The reaction sequence in Figure 1, if one ignores the steps implied by the open arrows, results in the synthesis of acetic acid from CO2 and H2: It is a catalytic cycle in which a complicated sequence of enzymatic reactions is used to bring about indirectly a reaction that looks simple on paper, but is not easily achieved in practice... It has not been suggested that the nonautocatalytic cycle alone was a source of prebiotic self-organization on the primitive Earth... This is a relatively easy reduction reaction, and it is reasonable to assume that it could proceed quickly in the presence of a mineral catalyst... A similar reduction occurs in the second step of reaction 7... Similarly, the splitting of malic acid to glyoxylic acid and acetic acid would return acetic acid to the cycle, but only at a cost in efficiency... A possibly more serious problem is posed by the difficult reductive carboxylation reactions... So far, I have treated autocatalytic chemical cycles as particularly sophisticated prebiotic reaction sequences that result in the amplified production of potentially useful organic molecules... In practice, this would not happen... The mistaken conclusion arises in part from assuming a value of 1.2 kcal/mol for the free energy of hydrolysis of a peptide bond, rather than a value of about 2.4 kcal/mol, as suggested by recent experiments... A more serious misunderstanding concerns the effect on peptide bond formation of replacing a 1 M solution of a single amino acid by a solution of a mixture of amino acids... Kaufmann's conclusions would only be true if each amino acid in the mixture was present at a concentration of 1 M... These findings, however, cannot support Kauffman's theory unless the prebiotic synthesis of the specific 15mer and 17mer input peptides from monomeric amino acids can be explained... Would one expect similar discrimination in the catalytic potential of peptides of length ten or less? The answer is clearly “no,” and it is this conclusion that ultimately undermines the peptide cycle theory... One must therefore consider the discrimination that would be needed to make the cycle theory plausible and then explain why short peptides are extremely unlikely to exhibit the necessary catalytic specificities.

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The Reverse (Reductive) Citric Acid CycleOnly the carbon species are shown, but the cycle also consumes four molecules of H2 and generates two molecules of H2O per turn. The main cycle (reactions 1–9) becomes autocatalytic if coupled to an epicycle that returns acetate to oxaloacetate (reactions 10 and 11).
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pbio-0060018-g001: The Reverse (Reductive) Citric Acid CycleOnly the carbon species are shown, but the cycle also consumes four molecules of H2 and generates two molecules of H2O per turn. The main cycle (reactions 1–9) becomes autocatalytic if coupled to an epicycle that returns acetate to oxaloacetate (reactions 10 and 11).

Mentions: The metabolic cycles that have been identified by biochemists are of two kinds: simple cycles and autocatalytic cycles. The citric acid cycle, which brings about the oxidation of acetate to CO2 with the concomitant synthesis of ATP, and the urea cycle that results in the conversion of toxic NH3 to relatively harmless urea, are both examples of simple cycles. The initial step of the former cycle is the synthesis of citric acid from oxaloacetic acid and acetyl-CoA. After one turn of the cycle, acetate is completely “burned” to CO2 as one molecule of oxaloacetate is regenerated. The Calvin dark cycle and the reverse citric acid cycle, both of which result in the fixation of CO2 into important biochemical intermediates, are examples of autocatalytic cycles. The reverse (reductive) citric acid cycle (Figure 1) is initiated by the splitting of citric acid to give oxaloacetic acid and acetyl-CoA. After one turn of the cycle, two molecules of citric acid are formed, so long as no material is diverted from the cycle. That is why the cycle is described as autocatalytic—each molecule of citric acid introduced into the cycle results, after a turn of the cycle, in the generation of two molecules of citric acid. The proposal that the reverse citric acid cycle operated nonenzymatically on the primitive Earth has been a prominent feature of some scenarios for the origin of life [6–8].


The implausibility of metabolic cycles on the prebiotic Earth.

Orgel LE - PLoS Biol. (2008)

The Reverse (Reductive) Citric Acid CycleOnly the carbon species are shown, but the cycle also consumes four molecules of H2 and generates two molecules of H2O per turn. The main cycle (reactions 1–9) becomes autocatalytic if coupled to an epicycle that returns acetate to oxaloacetate (reactions 10 and 11).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2211548&req=5

pbio-0060018-g001: The Reverse (Reductive) Citric Acid CycleOnly the carbon species are shown, but the cycle also consumes four molecules of H2 and generates two molecules of H2O per turn. The main cycle (reactions 1–9) becomes autocatalytic if coupled to an epicycle that returns acetate to oxaloacetate (reactions 10 and 11).
Mentions: The metabolic cycles that have been identified by biochemists are of two kinds: simple cycles and autocatalytic cycles. The citric acid cycle, which brings about the oxidation of acetate to CO2 with the concomitant synthesis of ATP, and the urea cycle that results in the conversion of toxic NH3 to relatively harmless urea, are both examples of simple cycles. The initial step of the former cycle is the synthesis of citric acid from oxaloacetic acid and acetyl-CoA. After one turn of the cycle, acetate is completely “burned” to CO2 as one molecule of oxaloacetate is regenerated. The Calvin dark cycle and the reverse citric acid cycle, both of which result in the fixation of CO2 into important biochemical intermediates, are examples of autocatalytic cycles. The reverse (reductive) citric acid cycle (Figure 1) is initiated by the splitting of citric acid to give oxaloacetic acid and acetyl-CoA. After one turn of the cycle, two molecules of citric acid are formed, so long as no material is diverted from the cycle. That is why the cycle is described as autocatalytic—each molecule of citric acid introduced into the cycle results, after a turn of the cycle, in the generation of two molecules of citric acid. The proposal that the reverse citric acid cycle operated nonenzymatically on the primitive Earth has been a prominent feature of some scenarios for the origin of life [6–8].

View Article: PubMed Central - PubMed

Affiliation: The Salk Institute for BiologicalStudies, San Diego, California, United States ofAmerica. gjoyce@scripps.edu

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

The reaction sequence in Figure 1, if one ignores the steps implied by the open arrows, results in the synthesis of acetic acid from CO2 and H2: It is a catalytic cycle in which a complicated sequence of enzymatic reactions is used to bring about indirectly a reaction that looks simple on paper, but is not easily achieved in practice... It has not been suggested that the nonautocatalytic cycle alone was a source of prebiotic self-organization on the primitive Earth... This is a relatively easy reduction reaction, and it is reasonable to assume that it could proceed quickly in the presence of a mineral catalyst... A similar reduction occurs in the second step of reaction 7... Similarly, the splitting of malic acid to glyoxylic acid and acetic acid would return acetic acid to the cycle, but only at a cost in efficiency... A possibly more serious problem is posed by the difficult reductive carboxylation reactions... So far, I have treated autocatalytic chemical cycles as particularly sophisticated prebiotic reaction sequences that result in the amplified production of potentially useful organic molecules... In practice, this would not happen... The mistaken conclusion arises in part from assuming a value of 1.2 kcal/mol for the free energy of hydrolysis of a peptide bond, rather than a value of about 2.4 kcal/mol, as suggested by recent experiments... A more serious misunderstanding concerns the effect on peptide bond formation of replacing a 1 M solution of a single amino acid by a solution of a mixture of amino acids... Kaufmann's conclusions would only be true if each amino acid in the mixture was present at a concentration of 1 M... These findings, however, cannot support Kauffman's theory unless the prebiotic synthesis of the specific 15mer and 17mer input peptides from monomeric amino acids can be explained... Would one expect similar discrimination in the catalytic potential of peptides of length ten or less? The answer is clearly “no,” and it is this conclusion that ultimately undermines the peptide cycle theory... One must therefore consider the discrimination that would be needed to make the cycle theory plausible and then explain why short peptides are extremely unlikely to exhibit the necessary catalytic specificities.

Show MeSH