Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 114, Issue 28, Pages 7403-7407Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1702274114
Keywords
origin of metabolism; gluconeogenesis; metabolism; evolution; nonenzymatic reactions
Categories
Funding
- University of Cambridge/Wellcome Trust Interdisciplinary fellowship
- Francis Crick Institute
- Cancer Research UK [FC001134]
- UK Medical Research Council [FC001134]
- Wellcome Trust [FC001134]
- MRC [MC_UP_1202/8, MC_U117533887] Funding Source: UKRI
- Medical Research Council [MC_UP_1202/8, MC_U117533887] Funding Source: researchfish
- The Francis Crick Institute [200829/Z/16/Z, 10029, 10134, 10012] Funding Source: researchfish
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available