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Amino acid fermentation at the origin of the genetic code.

de Vladar HP - Biol. Direct (2012)

Bottom Line: This redox reaction results in two keto acids that are employed to synthesise ATP via substrate-level phosphorylation.In all cases, donor amino acids are assigned to anticodons composed of U+G, and have low redundancy (1-2 codons), whereas acceptor amino acids are assigned to the the remaining codons.These bioenergetic and structural constraints allow for a metabolic role for amino acids before their co-option as catalyst cofactors.

View Article: PubMed Central - HTML - PubMed

Affiliation: hpvladar@ist.ac.at

ABSTRACT
There is evidence that the genetic code was established prior to the existence of proteins, when metabolism was powered by ribozymes. Also, early proto-organisms had to rely on simple anaerobic bioenergetic processes. In this work I propose that amino acid fermentation powered metabolism in the RNA world, and that this was facilitated by proto-adapters, the precursors of the tRNAs. Amino acids were used as carbon sources rather than as catalytic or structural elements. In modern bacteria, amino acid fermentation is known as the Stickland reaction. This pathway involves two amino acids: the first undergoes oxidative deamination, and the second acts as an electron acceptor through reductive deamination. This redox reaction results in two keto acids that are employed to synthesise ATP via substrate-level phosphorylation. The Stickland reaction is the basic bioenergetic pathway of some bacteria of the genus Clostridium. Two other facts support Stickland fermentation in the RNA world. First, several Stickland amino acid pairs are synthesised in abiotic amino acid synthesis. This suggests that amino acids that could be used as an energy substrate were freely available. Second, anticodons that have complementary sequences often correspond to amino acids that form Stickland pairs. The main hypothesis of this paper is that pairs of complementary proto-adapters were assigned to Stickland amino acids pairs. There are signatures of this hypothesis in the genetic code. Furthermore, it is argued that the proto-adapters formed double strands that brought amino acid pairs into proximity to facilitate their mutual redox reaction, structurally constraining the anticodon pairs that are assigned to these amino acid pairs. Significance tests which randomise the code are performed to study the extent of the variability of the energetic (ATP) yield. Random assignments can lead to a substantial yield of ATP and maintain enough variability, thus selection can act and refine the assignments into a proto-code that optimises the energetic yield. Monte Carlo simulations are performed to evaluate the establishment of these simple proto-codes, based on amino acid substitutions and codon swapping. In all cases, donor amino acids are assigned to anticodons composed of U+G, and have low redundancy (1-2 codons), whereas acceptor amino acids are assigned to the the remaining codons. These bioenergetic and structural constraints allow for a metabolic role for amino acids before their co-option as catalyst cofactors.

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The Stickland reaction. In the genus Clostridium, amino acid fermentation requires two steps. (A) Oxidative deamination of the amino acid with the higher oxidation state yields an α-keto acid, ammonium, and two protons. For example, if R1 is a methyl group (-CH3), then the donor amino acid is an alanine, and the product of the oxidative deamination would be pyruvate, a central compounds of the intermediary metabolism. (B) Inorganic phosphate attaches at the carboxyl terminus. The second proton takes the place of the amino radical. The product of this reaction is an acyl-phosphate. For example when R2 is a hydrogen (thus the acceptor amino acid is a glycine) this product corresponds to acetyl-phosphate. The two phosphate compounds from A and B are substrates for the synthesis of ATP from ADP. Naturally, in Clostridium spp. all these reactions occur with the aid of hydrogenases (for the electron donors) and reductases (for the electron acceptors). ATP synthesis is catalysed by kinases. However, in chemo-autotrophic systems, the acetyl-phosphate is readily the energy carrier (see text).
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Figure 3: The Stickland reaction. In the genus Clostridium, amino acid fermentation requires two steps. (A) Oxidative deamination of the amino acid with the higher oxidation state yields an α-keto acid, ammonium, and two protons. For example, if R1 is a methyl group (-CH3), then the donor amino acid is an alanine, and the product of the oxidative deamination would be pyruvate, a central compounds of the intermediary metabolism. (B) Inorganic phosphate attaches at the carboxyl terminus. The second proton takes the place of the amino radical. The product of this reaction is an acyl-phosphate. For example when R2 is a hydrogen (thus the acceptor amino acid is a glycine) this product corresponds to acetyl-phosphate. The two phosphate compounds from A and B are substrates for the synthesis of ATP from ADP. Naturally, in Clostridium spp. all these reactions occur with the aid of hydrogenases (for the electron donors) and reductases (for the electron acceptors). ATP synthesis is catalysed by kinases. However, in chemo-autotrophic systems, the acetyl-phosphate is readily the energy carrier (see text).

Mentions: My argument follows from three observations. First, amino acids are catabolised to obtain energy, and the metabolites are used as precursors for other biomolecules, a role often overlooked due to the prominent and central position of proteins in metabolism. This suggests that the amino acids could have originally had a bioenergetic, rather than catalytic role, with the latter appearing later. In particular, bacteria of the genus Clostridium are known to directly use amino acids to harvest metabolic energy. Some of these obligate anaerobes do not employ glucose as a carbon source, but rather ferment a pair of molecules; one amino acid acts as an electron donor and another acts as an electron acceptor. The overall reaction, termed Stickland fermentation releases energy the that powers the production of ATP (Figure 3). The substrates for the Stickland reaction are specific pairs of amino acids. That is, the reactants need to include one amino acid that can be oxidised (typically alanine, valine, leucine, serine, isoleucine or threonine), and another amino acid that can be reduced (typically glycine, proline, or aspartic acid; see Table 1) [8,9].


Amino acid fermentation at the origin of the genetic code.

de Vladar HP - Biol. Direct (2012)

The Stickland reaction. In the genus Clostridium, amino acid fermentation requires two steps. (A) Oxidative deamination of the amino acid with the higher oxidation state yields an α-keto acid, ammonium, and two protons. For example, if R1 is a methyl group (-CH3), then the donor amino acid is an alanine, and the product of the oxidative deamination would be pyruvate, a central compounds of the intermediary metabolism. (B) Inorganic phosphate attaches at the carboxyl terminus. The second proton takes the place of the amino radical. The product of this reaction is an acyl-phosphate. For example when R2 is a hydrogen (thus the acceptor amino acid is a glycine) this product corresponds to acetyl-phosphate. The two phosphate compounds from A and B are substrates for the synthesis of ATP from ADP. Naturally, in Clostridium spp. all these reactions occur with the aid of hydrogenases (for the electron donors) and reductases (for the electron acceptors). ATP synthesis is catalysed by kinases. However, in chemo-autotrophic systems, the acetyl-phosphate is readily the energy carrier (see text).
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Related In: Results  -  Collection

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Figure 3: The Stickland reaction. In the genus Clostridium, amino acid fermentation requires two steps. (A) Oxidative deamination of the amino acid with the higher oxidation state yields an α-keto acid, ammonium, and two protons. For example, if R1 is a methyl group (-CH3), then the donor amino acid is an alanine, and the product of the oxidative deamination would be pyruvate, a central compounds of the intermediary metabolism. (B) Inorganic phosphate attaches at the carboxyl terminus. The second proton takes the place of the amino radical. The product of this reaction is an acyl-phosphate. For example when R2 is a hydrogen (thus the acceptor amino acid is a glycine) this product corresponds to acetyl-phosphate. The two phosphate compounds from A and B are substrates for the synthesis of ATP from ADP. Naturally, in Clostridium spp. all these reactions occur with the aid of hydrogenases (for the electron donors) and reductases (for the electron acceptors). ATP synthesis is catalysed by kinases. However, in chemo-autotrophic systems, the acetyl-phosphate is readily the energy carrier (see text).
Mentions: My argument follows from three observations. First, amino acids are catabolised to obtain energy, and the metabolites are used as precursors for other biomolecules, a role often overlooked due to the prominent and central position of proteins in metabolism. This suggests that the amino acids could have originally had a bioenergetic, rather than catalytic role, with the latter appearing later. In particular, bacteria of the genus Clostridium are known to directly use amino acids to harvest metabolic energy. Some of these obligate anaerobes do not employ glucose as a carbon source, but rather ferment a pair of molecules; one amino acid acts as an electron donor and another acts as an electron acceptor. The overall reaction, termed Stickland fermentation releases energy the that powers the production of ATP (Figure 3). The substrates for the Stickland reaction are specific pairs of amino acids. That is, the reactants need to include one amino acid that can be oxidised (typically alanine, valine, leucine, serine, isoleucine or threonine), and another amino acid that can be reduced (typically glycine, proline, or aspartic acid; see Table 1) [8,9].

Bottom Line: This redox reaction results in two keto acids that are employed to synthesise ATP via substrate-level phosphorylation.In all cases, donor amino acids are assigned to anticodons composed of U+G, and have low redundancy (1-2 codons), whereas acceptor amino acids are assigned to the the remaining codons.These bioenergetic and structural constraints allow for a metabolic role for amino acids before their co-option as catalyst cofactors.

View Article: PubMed Central - HTML - PubMed

Affiliation: hpvladar@ist.ac.at

ABSTRACT
There is evidence that the genetic code was established prior to the existence of proteins, when metabolism was powered by ribozymes. Also, early proto-organisms had to rely on simple anaerobic bioenergetic processes. In this work I propose that amino acid fermentation powered metabolism in the RNA world, and that this was facilitated by proto-adapters, the precursors of the tRNAs. Amino acids were used as carbon sources rather than as catalytic or structural elements. In modern bacteria, amino acid fermentation is known as the Stickland reaction. This pathway involves two amino acids: the first undergoes oxidative deamination, and the second acts as an electron acceptor through reductive deamination. This redox reaction results in two keto acids that are employed to synthesise ATP via substrate-level phosphorylation. The Stickland reaction is the basic bioenergetic pathway of some bacteria of the genus Clostridium. Two other facts support Stickland fermentation in the RNA world. First, several Stickland amino acid pairs are synthesised in abiotic amino acid synthesis. This suggests that amino acids that could be used as an energy substrate were freely available. Second, anticodons that have complementary sequences often correspond to amino acids that form Stickland pairs. The main hypothesis of this paper is that pairs of complementary proto-adapters were assigned to Stickland amino acids pairs. There are signatures of this hypothesis in the genetic code. Furthermore, it is argued that the proto-adapters formed double strands that brought amino acid pairs into proximity to facilitate their mutual redox reaction, structurally constraining the anticodon pairs that are assigned to these amino acid pairs. Significance tests which randomise the code are performed to study the extent of the variability of the energetic (ATP) yield. Random assignments can lead to a substantial yield of ATP and maintain enough variability, thus selection can act and refine the assignments into a proto-code that optimises the energetic yield. Monte Carlo simulations are performed to evaluate the establishment of these simple proto-codes, based on amino acid substitutions and codon swapping. In all cases, donor amino acids are assigned to anticodons composed of U+G, and have low redundancy (1-2 codons), whereas acceptor amino acids are assigned to the the remaining codons. These bioenergetic and structural constraints allow for a metabolic role for amino acids before their co-option as catalyst cofactors.

Show MeSH