Chemical Constraints Governing the Origin of Metabolism: The Thermodynamic Landscape of Carbon Group Transformations under Mild Aqueous Conditions

The thermodynamics of organic chemistry under mildaqueous conditions was examined in order to begin to understand itsinfluence on the structure and operation of metabolism and itsantecedents. Free energies (G) were estimated for four types ofreactions of biochemical importance – carbon-carbon bond cleavage andsynthesis, hydrogen transfer between carbon groups, dehydration ofalcohol groups, and aldo-keto isomerization. The energies werecalculated for mainly aliphatic groups composed of carbon, hydrogen,and oxygen. The energy values showed (1) that generally when carbon-carbon bond cleavage involves groups from different functional groupclasses (i.e., carboxylic acids, carbonyl groups, alcohols, andhydrocarbons), the transfer of the shared electron-pair to the morereduced carbon group is energetically favored over transfer to themore oxidized carbon group, and (2) that the energy of carbon-carbonbond transformation is primarily determined by the functional groupclass of the group that changes oxidation state in the reaction (i.e., the functional group class of the group that donates the sharedelectron-pair during cleavage, or that accepts the incipient sharedelectron-pair during synthesis). In contrast, the energy of hydrogentransfer between carbon groups is determined by the functional groupclass of both the hydrogen-donor group and the hydrogen-acceptorgroup. From these and other observations we concluded that thechemistry involved in the origin of metabolism (and to a lesser degreemodern metabolism) was strongly constrained by (1) the limited redox-based transformation energy of organic substrates that is readilydissipated in a few energetically favorable irreversible reactions;(2) the energy dominance of a few transformation half-reactions thatdetermines whether carbon-carbon bond transformation (cleavage orsynthesis) is energetically favorable (G < –3.5 kcal/mol), reversible(G between ±3.5 kcal/mol), or unfavorable (G > +3.5 kcal/mol);and (3) the dependence of carbon group transformation energy on thefunctional group class (i.e., oxidation state) of participatinggroups that in turn is contingent on prior reactions and precursors inthe synthetic pathway.