Prebiotic formation of ‘energy-rich’ thioesters from glyceraldehyde and N-acetylcysteine

Abstract

The 'energy-rich' thioester, N-acetyl-S-lactoylcysteine, is formed from low concentrations of glyceraldehyde and N-acetylcysteine under anaerobic conditions at ambient temperature in aqueous solutions of sodium phosphate (pH 7.0). Reactions with 2 mM glyceraldehyde, 2 mM N-acetylcysteine, and 500 mM sodium phosphate (pH 7.0) convert about 3%/day of the glyceraldehyde to lactoyl thioester. The formation of lactoyl thioester in similar reactions with 500 mM imidazole hydrochloride (pH 7.0) is supported by the thiol-dependence of lactate formation, which is 3-fold greater in the presence of thiol (0.11%/day) than in the absence of thiol (0.04%/day). The formation of lactoyl thioester is thought to proceed by the phosphate (or imidazole)-catalyzed dehydration of glyceraldehyde to give pyruvaldehyde, which adds to the thiol to form a hemithioacetal that rearranges to the thioester. A limited amount of a second thioester, N-acetyl-S-glyceroyl-cycsteine, is also formed at the beginning of these reactions. The significance of these reactions to the origin of life is discussed.

The Relative Rates of Thiol–Thioester Exchange and Hydrolysis for Alkyl and Aryl Thioalkanoates in Water

“…Various experimental studies have reported the synthesis of thioesters under possible primordial conditions (Weber 1984(Weber , 1998. S-methyl thioacetate (2) is the simplest example of a thioester, and the kinetics of its hydrolysis are especially pertinent to origin-of-life chemistry.…”

Activity of the Yap1 Transcription Factor in Saccharomyces cerevisiae Is Modulated by Methylglyoxal, a Metabolite Derived from Glycolysis

“…Therefore, arginine and lysine residues in protein may be preferentially modified by MG compared to cysteine residues, and modification of cysteine residues by MG may be labile and/or reversible. The chemical reaction between a thiol group and aldehyde at physiological pH yields hemithioacetal (62). For example, MG nonenzymatically condenses with glutathione to form hemithioacetal reversibly (K d ϭ 1 ϫ 10 Ϫ3 M) (60).…”

The Sugar Model: Autocatalytic Activity of the Triose–Ammonia Reaction

“…Autocatalytic Activity of the Triose-Ammonia Reaction Product Previous investigations have shown that sugar-ammonia reactions yield small molecules (amines and organic acids) that are known from separate studies to catalyze various sugar transformations (Grimmett 1965;Kort 1970;Weber 1984Weber , 1985Weber , 1998Ledl and Schleicher 1990). However, there have been no studies reporting catalysis of a sugar-ammonia reaction by its own chemical product.…”

“…As shown in the figure, the two reactions we measured are the reversible isomerization of glyceraldehyde to dihydroxyacetone (ΔG°′∼ −1 kcal/mol), and the irreversible β-dehydration of glyceraldehyde and dihydroxyacetone to pyruvaldehyde (ΔG°′∼ −11 kcal/mol) (Weber 2002(Weber , 2004. Other likely reactions are: (1) mixed aldol condensations involving trioses and pyruvaldehyde that generate branched and linear hexoses, 3-deoxyhexosuloses, and other dicarbonyl products (Gutsche et al 1967;Konigstein and Fedoronko 1973;Weber 2001), (2) anaerobic intra-and intermolecular redox reactions that convert trioses and pyruvaldehyde to organic acids such as glyoxylic acid, pyruvic acid, and lactic acid (Weber 1984(Weber , 1998, (3) α-ketoaldehyde deformylations that convert pyruvaldehyde to acetaldehyde and formic acid, and 3-deoxyhexosuloses to 2-deoxypentoses (like 2-deoxyribose) and formic acid (Ledl and Schleicher 1990;Weber 2001), and (4) dehydrations involving sugar hemiacetal rings that yield substituted furans (Ledl and Schleicher 1990;Gerrard 2002). Most of these types of sugar transformations are known to be catalyzed by amines, ammonia, and organic acids (Ledl and Schleicher 1990;Weber 2001).…”

“…therein). Sugars spontaneously react in the presence and absence of amines (or ammonia) to give numerous aliphatic and aromatic products, like hydroxy acids, pyruvate, amino acids, furans, imidazoles, pyridines, and pyrroles (Grimmett 1965;Kort 1970;Weber 1984Weber , 1985Weber , 1998Ledl and Schleicher 1990). Sugar transformations also yield melanoidin polymers (Ellis 1959;Cammerer et al 2002;Martins and Van Boekel 2005) that in some cases integrate into growing semi-solid microspherules (Weber 2005).…”