Nonenzymatic gluconeogenesis-like formation of fructose 1,6-bisphosphate in ice

The evolutionary origins of metabolism, in particular the emergence of the sugar phosphates that constitute glycolysis, the pentose phosphate pathway, and the RNA and DNA backbone, are largely unknown. In cells, a major source of glucose and the large sugar phosphates is gluconeogenesis. This ancient anabolic pathway (re-)builds carbon bonds as cleaved in glycolysis in an aldol condensation of the unstable catabolites glyceraldehyde 3-phosphate and dihydroxyacetone phosphate, forming the much more stable fructose 1,6-bisphosphate. We here report the discovery of a nonenzymatic counterpart to this reaction. The in-ice nonenzymatic aldol addition leads to the continuous accumulation of fructose 1,6-bisphosphate in a permanently frozen solution as followed over months. Moreover, the in-ice reaction is accelerated by simple amino acids, in particular glycine and lysine. Revealing that gluconeogenesis may be of nonenzymatic origin, our results shed light on how glucose anabolism could have emerged in early life forms. Furthermore, the amino acid acceleration of a key cellular anabolic reaction may indicate a link between prebiotic chemistry and the nature of the first metabolic enzymes.This work was supported by a University of Cambridge/Wellcome Trust Interdisciplinary fellowship (to C.B.M.). Further support was provided by the Francis Crick Institute, which receives its core funding from Cancer Research UK (Award FC001134), the UK Medical Research Council (Award FC001134), and the Wellcome Trust (Award FC001134)

Nonenzymatic gluconeogenesis-like formation of fructose 1,6-bisphosphate in ice

The evolutionary origins of metabolism, in particular the emergence of the sugar phosphates that constitute glycolysis, the pentose phosphate pathway, and the RNA and DNA backbone, are largely unknown. In cells, a major source of glucose and the large sugar phosphates is gluconeogenesis. This ancient anabolic pathway (re-)builds carbon bonds as cleaved in glycolysis in an aldol condensation of the unstable catabolites glyceraldehyde 3-phosphate and dihydroxyacetone phosphate, forming the much more stable fructose 1,6-bisphosphate. We here report the discovery of a nonenzymatic counterpart to this reaction. The in-ice nonenzymatic aldol addition leads to the continuous accumulation of fructose 1,6-bisphosphate in a permanently frozen solution as followed over months. Moreover, the in-ice reaction is accelerated by simple amino acids, in particular glycine and lysine. Revealing that gluconeogenesis may be of nonenzymatic origin, our results shed light on how glucose anabolism could have emerged in early life forms. Furthermore, the amino acid acceleration of a key cellular anabolic reaction may indicate a link between prebiotic chemistry and the nature of the first metabolic enzymes

Gravity modeling of the Muertos Trough and tectonic implications (north-eastern Caribbean)

The Muertos Trough in the northeast Caribbean has been interpreted as a subduction zone from seismicity, leading to infer a possible reversal subduction polarity. However, the distribution of the seismicity is very diffuse and makes definition of the plate geometry difficult. In addition, the compressive deformational features observed in the upper crust and sandbox kinematic modeling do not necessarily suggest a subduction process. We tested the hypothesized subduction of the Caribbean plate’s interior beneath the eastern Greater Antilles island arc using gravity modeling. Gravity models simulating a subduction process yield a regional mass deficit beneath the island arc independently of the geometry and depth of the subducted slab used in the models. This mass deficit results from sinking of the less dense Caribbean slab beneath the lithospheric mantle replacing denser mantle materials and suggests that there is not a subducted Caribbean plateau beneath the island arc. The geologically more realistic gravity model which would explain the N–S shortening observed in the upper crust requires an overthrusted Caribbean slab extending at least 60 km northward from the deformation front, a progressive increase in the thrusting angle from 8 to 30 reaching a maximum depth of 22 km beneath the insular slope. This new tectonic model for the Muertos Margin, defined as a retroarc thrusting, will help to assess the seismic and tsunami hazard in the region. The use of gravity modeling has provided targets for future wide-angle seismic surveys in the Muertos Margin