Kinetics of the hydrolysis of arsenate(V) triesters

Baer, Carl D.; Edwards, John O.; Rieger, Philip H.

doi:10.1021/ic50217a052

Cited by 32 publications

(44 citation statements)

References 2 publications

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“…Even though (a) has been shown to be feasible in a number of recent reports, 6,7 in the case of (b), there are many verified studies that argue arsenate ester is kinetically unstable in regard to hydrolysis. [3][4][5]11,12 In the present communication, we will show that the involved thermodynamics is also a great obstacle toward utilizing ATA or arsenate esters as energy carriers in biological systems.In this work, the energetics of adenosine mono/di/triphosphates, AnP (n = M, D, T), and their As-substituents were computationally studied. The computational details are described in the Supporting Information.…”

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confidence: 82%

“…3,5,11,12 Thus, we can infer that adopting ATA will likely suffer from two disadvantages, both kinetically and thermodynamically. This situation can be pictorially represented with phosphate/arsenate hydrolysis energetics as shown in Figure 1.…”

Section: 5mentioning

confidence: 99%

“…Even if environment in biological system such as enzymatic protein structure is optimized to stabilize arsenate esters, the hydrolysis energies of the As-analogs will likely limit their role as energy carriers. When this aspect is considered in combination with the already reported kinetic instability of arsenate esters and As-DNA, 3,5,11,12 it is unlikely that Assubstituted analogs will be functional as replacements of conventional phosphorylated adenosine compounds. If Asbased life should exist, they will have to survive with a new mechanism and/or different chemical species other than ATA as an energy carrier.…”

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Can Adenosine Triarsenate Role as an Energy Carrier?

Park¹,

Rhee²,

Kim³

2013

Bulletin of the Korean Chemical Society

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Recently, Wolfe-Simon et al. reported the existence of a bacterium species, GFAJ-1, which can grow using arsenic (As) instead of phosphorus (P).1,2 If this is true, despite many objections that have risen, 3-5 it will revolutionize our knowledge of biochemistry and may even open a new door to the search for the existence of extraterrestrial life. However, before getting thrilled by this new discovery, we will have to investigate various aspects of many essential biomolecules when their P contents are replaced with As. In the case of DNA, which is definitely one of the core molecules in life, Denning et al. 6 and Mládek et al. 7 investigated the effect of the As-substitution and concluded that it induces no critical effect on the DNA backbone structure, although hydrolysis of this backbone will likely be quite rapid. 3,5One additional core biomolecule is adenosine triphosphate (ATP), which takes the role of an energy carrier of essentially all life forms. Many biochemical reactions are coupled with hydrolysis of ATP and phosphorylation, as ATP has high-energy phosphate bonds and releases a large amount of free energy (ΔG o = −7.3 kcal/mol 8 ) upon the reaction. If Asbased organism is possible, they will possess adenosine triarsenate (ATA) instead of ATP since there will be no or little P content to form ATP. Even forming the formerly discovered adenosine diphosphate arsenate (ADP-Asi) 2,9,10 will be unlikely under a harsh condition without any P in the environment. If the organism has adopted As as a brick of forming various biomolecules and/or as mortar for gluing them, ATA should (a) be structurally similar with ATP so that the relevant enzymes can adopt a similar mechanism as in the ATP case, (b) be stable enough to function regularly in biochemical systems, and (c) release a large enough amount of free energy during the hydrolysis reaction. Even though (a) has been shown to be feasible in a number of recent reports, 6,7 in the case of (b), there are many verified studies that argue arsenate ester is kinetically unstable in regard to hydrolysis. [3][4][5]11,12 In the present communication, we will show that the involved thermodynamics is also a great obstacle toward utilizing ATA or arsenate esters as energy carriers in biological systems.In this work, the energetics of adenosine mono/di/triphosphates, AnP (n = M, D, T), and their As-substituents were computationally studied. The computational details are described in the Supporting Information. Ideally, for exact comparisons, we need to calculate free energy changes of the relevant reactions, which are computationally too demanding in many cases especially for quantum chemical approaches. However, because conformations of As-substituted compounds are close to the P-containing biological analogs, 6,7 we can assume that the contributions from the internal degrees of freedom toward the reaction entropies will be similar for both P and As-containing compounds. By additionally assuming that the solvent-related contributions will be mostly recovered from the implic...

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Can Adenosine Triarsenate Role as an Energy Carrier?

Park¹,

Rhee²,

Kim³

2013

Bulletin of the Korean Chemical Society

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“…The arguments by Benner and others about the stability of arsenate esters (3,5,7), based on the rapidity of hydrolysis of small model compounds (23)(24)(25), challenge the plausibility of As-substituted biomolecules and biosynthetic pathways (26). However, we note that arsenate esters of large biomolecules are likely to be more sterically hindered, leading to slower rates of hydrolysis than occurs in small compounds, which are relatively flexible and can adopt a geometry that allows water to attack the arseno-ester bond.…”

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confidence: 99%

“…However, we note that arsenate esters of large biomolecules are likely to be more sterically hindered, leading to slower rates of hydrolysis than occurs in small compounds, which are relatively flexible and can adopt a geometry that allows water to attack the arseno-ester bond. There is little literature on the stability of arsenate bound in long chain polyesters or nucleotide di-or triesters, which are more relevant to our studies, but there is evidence that the hydrolysis rates for simple alkyl triesters of arsenate decrease with increasing complexity of the alkyl substituent (methyl > ethyl > n-pentyl > isopropyl) (23). It is therefore conceivable that arsenate-linked biopolymers are more resistant to hydrolysis than generally assumed, perhaps sufficiently so for an As-adapted organism to cope with some degree of As substitution.…”

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Response to Comments on “A Bacterium That Can Grow Using Arsenic Instead of Phosphorus”

Wolfe-Simon

Blum

Kulp

et al. 2011

Science

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Concerns have been raised about our recent study suggesting that arsenic (As) substitutes for phosphorus in major biomolecules of a bacterium that tolerates extreme As concentrations. We welcome the opportunity to better explain our methods and results and to consider alternative interpretations. We maintain that our interpretation of As substitution, based on multiple congruent lines of evidence, is viable. O ur study (1) described the ability of a known microbe, a member of the Gammaproteobacteria (strain GFAJ-1), to survive and grow in the presence of 40 mM arsenate (As) when cultured without deliberately added phosphate (P). We hypothesized that GFAJ-1 incorporates As into biomolecules in place of P, based on evidence ranging from mass spectrometry and x-ray spectroscopy to classical techniques in microbiology. Here, we address specific concerns raised about our procedures and interpretation (2-9).The foundation of our study was a suite of microbial growth experiments demonstrating extreme As tolerance and enhanced growth in +As/-P media as compared with -As/-P controls (1). These experiments have been criticized because of the presence of trace P in the experimental media. Benner (3) suggests that this contamination came as an impurity with the As added to +As/-P experiments and that the level of contamination is unknown. If this were so, the experiments would be fundamentally flawed; however, to clarify the methods described in the Supporting Online Material (SOM) accompanying our original study (1), medium mineral salts were initially made up as -As/-P, without added vitamins or glucose. The P content of the batch of this mixture used in all experiments was 3.7 T 0.8 mM (T2 SD; table S1, 5 April 2010 batch) (1). For every experiment, vitamins, glucose, and either P or As were added to this mixture, as described in "Materials and Methods" in the SOM (1). In the two batches of medium to which we added As along with glucose and vitamins, we measured P contents of 2.9 T 0.6 and 2.7 T 0.6 mM (table S1) (1). These values are statistically indistinguishable from the P content of the -As/-P mineral salt medium. Therefore, the P background presumably came from the mineral salts, not from the added As, and was effectively identical in all treatments (~3 mM).Several comments suggest or imply that this background P was sufficient to sustain growth in the +As/-P experiments (2,3,5,6,8,9). We do not find these arguments compelling given the poor growth in the control experiment compared with the +As/-P experiment, both of which contained the same P background. Any alternative hypothesis must account for this basic observation.Foster (9) hypothesizes that the enhanced growth we observed upon addition of As compared with the -As/-P control can be explained if we inadvertently selected for a microbe that retains a high-affinity P uptake mechanism (Pst) that is stimulated by arsenate. If operational, we would expect evidence of arsenate detoxification processes, such as arsenate reduction or methylation, because all phosph...

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