The Messy Alkaline Formose Reaction and Its Link to Metabolism

Abstract

Sugars are essential for the formation of genetic elements such as RNA and as an energy/food source. Thus, the formose reaction, which autocatalytically generates a multitude of sugars from formaldehyde, has been viewed as a potentially important prebiotic source of biomolecules at the origins of life. When analyzing our formose solutions we find that many of the chemical species are simple carboxylic acids, including α-hydroxy acids, associated with metabolism. In this work we posit that the study of the formose reaction, under alkaline conditions and moderate hydrothermal temperatures, should not be solely focused on sugars for genetic materials, but should focus on the origins of metabolism (via metabolic molecules) as well.

Prebiotic Pathway from Ribose to RNA Formation

“…Intermediary steps of the formose reaction involved aldol condensations, aldose-ketose isomerizations producing glycolaldehyde, glyceraldehyde, dihydroxyacetone, tetrose, pentose, and hexose. In agreement with Omran et al [ 9 ], the study of the formose reaction, under alkaline conditions and moderate hydrothermal temperatures, should not solely focus on sugars, particularly ribose as part of the genetic material, but also on the origins of metabolism via other metabolic molecules. An increasing number of scientists think that the generation of the genetic material developed from the formose reaction to ribose and RNA [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ].…”

Cysteine and iron accelerate the formation of ribose-5-phosphate, providing insights into the evolutionary origins of the metabolic network structure

“…Although the exact chemistry behind the nonoxidative reactions remains to be fully elaborated, the described system is thought to establish the upper intermediates of the PPP and EMP pathways via a series of reactions observed in Maillard reactions as well as thiol-mediated oxidation reactions [ 77 ]. In addition, several of the 6-carbon phosphate carbohydrates could have formed recursively from condensation reactions in freeze-thaw cycles under plausible prebiotic conditions [ 22 , 78 ]. Cysteine sulfur condenses with a carbonyl functionality allowing for the facile dehydrogenation of glucose 6-phosphate.…”

Thermodynamics of Potential CHO Metabolites in a Reducing Environment

“…This similarity in energy between the acid and aldehyde may be an important feature in proto-metabolism by allowing essentially energy-neutral and thus thermodynamically reversible redox transformations, possibly aided by primitive redox catalysts. We previously alluded to this feature: acids, aldehydes and ketones potentially form an equilibrating pool of molecules that may exert some control and regulation [36,37]. To this, we might add esters and anhydrides that might allow for the sequestering of acid metabolites.…”

“…(2) Because the C 2 "recycling" species (GA) and the C 1 "food" species (CH 2 O) are both at oxidation state zero, additional redox reactions are not required, thereby simplifying the situation. (3) Cannizzaro reactions (such as 2 CH 2 O + H 2 O → HCO 2 H + CH 3 OH) can be parasitic on the cycle, but also provide access to compounds with a wider range of oxidation states; and experimentally the formose reaction generates a range of carboxylic acids [37], including those found in extant biochemistry.…”

“…Glycolic acid is produced in measurable quantities in formose reactions [37], Miller spark-discharge experiments [38], and plays a potential role as a scaffold in oligopeptideforming chemistry [39]. Could it play a role as the recycling C 2 compound instead of ACE?…”