How Prebiotic Chemistry and Early Life Chose Phosphate

Abstract

The very specific thermodynamic instability and kinetic stability of phosphate esters and anhydrides impart them invaluable properties in living organisms in which highly efficient enzyme catalysts compensate for their low intrinsic reactivity. Considering their role in protein biosynthesis, these properties raise a paradox about early stages: How could these species be selected in the absence of enzymes? This review is aimed at demonstrating that considering mixed anhydrides or other species more reactive than esters and anhydrides can help in solving the paradox. The consequences of this approach for chemical evolution and early stages of life are analysed.

Keywords: energy currency; metabolism; mixed anhydride; phosphoryl transfer.

Figure 1

Hydrolysis of phosphate diesters. Nucleophilic attack can take place at carbon or phosphorus depending on the degree of substitution at carbon.

Figure 2

The dissociative pathway of phosphoryl transfer in the hydrolysis of phosphate monoesters. A metaphosphate ion (PO₃⁻) intermediate or at least resonance stabilization at the transition state is involved in the reaction.

Figure 3

ATP and pyrophosphate have been proposed as prebiotic energy currencies, in spite of the kinetic barrier hindering their reactions with nucleophiles at moderate pH values at which they are negatively charged.

Figure 4

Amino acyl phosphates and aminoacyl adenylates are highly activated biochemicals.

Figure 5

Phosphate esters mixed anhydrides suffer from stabilization against reaction with nucleophiles as other phosphate derivatives. The pathway involving N-carboxyanhydrides (NCAs) as intermediates must be taken into consideration as soon as CO₂ is present in the atmosphere, even at low levels.

Figure 6

Phosphoramidate derivatives of amino acids and the ester- and phosphoramidate-based structures constituting the basis of prebiotically plausible copolymers.

Figure 7

An energy currency (activated form EC*) formed from a currency precursor (CP) requires a high free energy potential and pathways available to transfer energy between different processes faster than the dissipation of energy. Energy currencies must therefore comply with kinetic and thermodynamic requirements.

Figure 8

Phosphorylation can by promoted by electrophilic activating agent capable of generation an intermediate capable of transferring the phosphoryl group to an acceptor nucleophile through a metaphosphate or, at least, resonance-stabilized intermediate.

Figure 9

Cyanate-promoted phosphorylation through a carbamyl phosphate intermediate.