Formation of methylglyoxal (CH3C(O)CHO) in interstellar analog ices - a key intermediate in cellular metabolism.

Ketoaldehydes are key intermediates in biochemical processes including carbohydrate, lipid, and amino acid metabolism. Despite their crucial role in the interstellar synthesis of essential biomolecules necessary for the Origins of Life, their formation mechanisms have largely remained elusive. Here, we report the first bottom-up formation of methylglyoxal (CH3C(O)CHO)-the simplest ketoaldehyde-through the barrierless recombination of the formyl (HCO) radical with the acetyl (CH3CO) radical in low-temperature interstellar ice analogs upon exposure to energetic irradiation as proxies of galactic cosmic rays. Utilizing vacuum ultraviolet photoionization reflectron time-of-flight mass spectrometry and isotopic substitution studies, methylglyoxal and its enol tautomer 2-hydroxypropenone (CH3C(OH)CO) were identified in the gas phase during the temperature-programmed desorption of irradiated carbon monoxide-acetaldehyde (CO-CH3CHO) ices, suggesting their potential as promising candidates for future astronomical searches. Once synthesized in cold molecular clouds, methylglyoxal can serve as a key precursor to sugars, sugar acids, and amino acids. Furthermore, this work provides the first experimental evidence for tautomerization of a ketoaldehyde in interstellar ice analogs, advancing our fundamental knowledge of how ketoaldehydes and their enol tautomers can be synthesized in deep space.

The action of coenzyme B12-dependent diol dehydratase on 3,3,3-trifluoro-1,2-propanediol results in elimination of all the fluorides with formation of acetaldehyde.

3,3,3-Trifluoro-1,2-propanediol undergoes complete defluorination in two distinct steps: first, the conversion into 3,3,3-trifluoropropionaldehyde catalyzed by adenosylcobalamin (coenzyme B12)-dependent diol dehydratase; second, non-enzymatic elimination of all three fluorides from this aldehyde to afford malonic semialdehyde (3-oxopropanoic acid), which is decarboxylated to acetaldehyde. Diol dehydratase accepts 3,3,3-trifluoro-1,2-propanediol as a relatively poor substrate, albeit without significant mechanism-based inactivation of the enzyme during catalysis. Optical and electron paramagnetic resonance (EPR) spectra revealed the steady-state formation of cob(II)alamin and a substrate-derived intermediate organic radical (3,3,3-trifluoro-1,2-dihydroxyprop-1-yl). The coenzyme undergoes Co-C bond homolysis initiating a sequence of reaction by the generally accepted pathway via intermediate radicals. However, the greater steric size of trifluoromethyl and especially its negative impact on the stability of an adjacent radical centre compared to a methyl group has implications for the mechanism of the diol dehydratase reaction. Nevertheless, 3,3,3-trifluoropropionaldehyde is formed by the normal diol dehydratase pathway, but then undergoes non-enzymatic conversion into acetaldehyde, probably via 3,3-difluoropropenal and malonic semialdehyde.

Structure of the iminium reaction intermediate in an engineered aldolase explains the carboligation activity toward arylated ketones and aldehydes.

Two structures of fructose 6-phosphate aldolase, the wild-type and an engineered variant containing five active-site mutations, have been solved by cryoelectron microscopy (cryo-EM). The engineered variant affords production of aldols from aryl substituted ketones and aldehydes. This structure was solved to a resolution of 3.1 Å and contains the critical iminium reaction intermediate trapped in the active site. This provides new information that rationalizes the acquired substrate scope and aids in formulating hypotheses of the chemical mechanism. A Tyr residue (Y131) is positioned for a role as catalytic acid/base during the aldol reaction and the different structures demonstrate mobility of this amino acid residue. Further engineering of this fructose 6-phosphate aldolase (FSA) variant, guided by this new structure, identified additional FSA variants that display improved carboligation activities with 2-hydroxyacetophenone and phenylacetaldehyde.

Comprehensive analysis of risk factors (methanol, acetaldehyde and higher alcohols) in alcoholic beverages and their reduction strategies: GC-MS analysis and modified activated carbon adsorption and characterization.

This study endeavors to examine the levels of risk factors in alcoholic beverages and propose mitigation strategies. GC-MS analysis was utilized to assess risk factors in various distilled-spirits. The content of such risk factors in spirits ranked as follows: vodka ≈ gin < baijiu < whiskey < brandy, and all were adhering to the Chinese national standard. Additionally, a method was refined to alleviate these risks, employing various reagents for activated carbon modification and evaluating their adsorption efficiency for risk factors reduction. Oxalic acid-modified activated carbon exhibited promising adsorption rates for risk factors with acceptable flavor compounds loss, rendering it a prospective solution for health hazard reduction. Characterization via SEM and nitrogen-adsorption-desorption was conducted on the optimal material, complemented by sensory experiments to optimize its application. This study offers valuable insights into the content of risk factors in alcoholic beverages, aiding in improving quality and safety of alcoholic beverages.

Nano zero valent iron stimulated acetaldehyde oxidation, electron transfer, and RBO pathway for enhanced medium-chain carboxylic acids production.

Nano zero-valent iron (NZVI) has been shown to effectively enhance the chain elongation (CE) process, addressing the issue of limited yield of medium-chain carboxylic acids (MCCA) from organic wastewater. However, the specific impact of NZVI on the metabolism of CE bacteria (CEB) is not well understood. In this study, it was aimed to investigate the mechanism by which an optimal concentration of NZVI influences CE metabolism, particularly in relation to ethanol oxidation, electron transfer, and MCCA synthesis. This was achieved through single-factor influence experiments and metagenomic analysis. The results showed that the addition of 1 g/gVSS NZVI achieved the highest MCCA yield (n-caproic acid + n-octanoic acid) at 2.02 g COD/L, which was 4.9 times higher than the control. This improvement in MCCA production induced by NZVI was attributed to several factors. Firstly, NZVI facilitated the oxidation of acetaldehyde, leading to its reduced accumulation in the system (from 18.4 % to 5.8 %), due to the optimized chemical environment created by NZVI corrosion, including near-neutral pH and a more reductive oxidation-reduction potential (ORP). Additionally, the inherent conductivity property of NZVI and the additional Fe ions released during corrosion improved the electron transfer efficiency between CEB. Lastly, both the composition of microbial communities and the abundance of unique enzyme genes confirmed the selective stimulation of NZVI on the reverse ß-oxidation (RBO) pathway. These findings provide valuable insights into the role of NZVI in CEB metabolism and its potential application for enhancing MCCA production in CE bioreactors.

A Prebiotic Pathway to Nicotinamide Adenine Dinucleotide.

Enzymes play a fundamental role in cellular metabolism. A wide range of enzymes require the presence of complementary coenzymes and cofactors to function properly. While coenzymes are believed to have been part of the last universal ancestor (LUCA) or have been present even earlier, the syntheses of crucial coenzymes like the redox-active coenzymes flavin adenine dinucleotide (FAD) or nicotinamide adenine dinucleotide (NAD+) remain challenging. Here, we present a pathway to NAD+ under prebiotic conditions starting with ammonia, cyanoacetaldehyde, prop-2-ynal and sugar-forming precursors, yielding in situ the nicotinamide riboside. Regioselective phosphorylation and water stable light activated adenosine monophosphate derivatives allow for topographically and irradiation-controlled formation of NAD+. Our findings indicate that NAD+, a coenzyme vital to life, can be formed non-enzymatically from simple organic feedstock molecules via photocatalytic activation under prebiotically plausible early Earth conditions in a continuous process under aqueous conditions.

Pitfalls in the Detection of Volatiles Associated with Heated Tobacco and e-Vapor Products When Using PTR-TOF-MS.

We investigated the applicability of proton transfer reaction-time-of-flight mass spectrometry (PTR-TOF-MS) for quantitative analysis of mixtures comprising glycerin, acetol, glycidol, acetaldehyde, acetone, and propylene glycol. While PTR-TOF-MS offers real-time simultaneous determination, the method selectivity is limited when analyzing compounds with identical elemental compositions or when labile compounds present in the mixture produce fragments that generate overlapping ions with other matrix components. In this study, we observed significant fragmentation of glycerin, acetol, glycidol, and propylene glycol during protonation via hydronium ions (H3O+). Nevertheless, specific ions generated by glycerin (m/z 93.055) and propylene glycol (m/z 77.060) enabled their selective detection. To thoroughly investigate the selectivity of the method, various mixtures containing both isotope-labeled and unlabeled compounds were utilized. The experimental findings demonstrated that when samples contained high levels of glycerin, it was not feasible to perform time-resolved analysis in H3O+ mode for acetaldehyde, acetol, and glycidol. To overcome the observed selectivity limitations associated with the H3O+ reagent ions, alternative ionization modes were investigated. The ammonium ion mode proved appropriate for analyzing propylene glycol (m/z 94.086) and acetone (m/z 76.076) mixtures. Concerning the nitric oxide mode, specific m/z were identified for acetaldehyde (m/z 43.018), acetone (m/z 88.039), glycidol (m/z 73.028), and propylene glycol (m/z 75.044). It was concluded that considering the presence of multiple product ions and the potential influence of other compounds, it is crucial to conduct a thorough selectivity assessment when employing PTR-TOF-MS as the sole method for analyzing compounds in complex matrices of unknown composition.

Abiotic Ribose Synthesis Under Aqueous Environments with Various Chemical Conditions.

Ribose is the defining sugar in ribonucleic acid (RNA), which is often proposed to have carried the genetic information and catalyzed the biological reactions of the first life on Earth. Thus, abiological processes that yield ribose under prebiotic conditions have been studied for decades. However, aqueous environments required for the formation of ribose from materials available in quantity under geologically reasonable models, where the ribose formed is not immediately destroyed, remain unclear. This is due in large part to the challenge of analysis of carbohydrates formed under a wide range of aqueous conditions. Thus, the formation of ribose on prebiotic Earth has sometimes been questioned. We investigated the quantitative effects of pH, temperature, cation, and the concentrations of formaldehyde and glycolaldehyde on the synthesis of diverse sugars, including ribose. The results suggest a range of conditions that produce ribose and that ribose could have formed in constrained aquifers on prebiotic Earth.

Substitution of both histidines in the active site of yeast alcohol dehydrogenase 1 exposes underlying pH dependencies.

Histidine residues 44 and 48 in yeast alcohol dehydrogenase (ADH) bind to the coenzymes NAD(H) and contribute to catalysis. The individual H44R and H48Q substitutions alter the kinetics and pH dependencies, and now the roles of other ionizable groups in the enzyme were studied in the doubly substituted H44R/H48Q ADH. The substitutions make the enzyme more resistant to inactivation by diethyl pyrocarbonate, modestly improve affinity for coenzymes, and substantially decrease catalytic efficiencies for ethanol oxidation and acetaldehyde reduction. The pH dependencies for several kinetic parameters are shifted from pK values for wild-type ADH of 7.3-8.1 to values for H44R/H48Q ADH of 8.0-9.6, and are assigned to the water or alcohol bound to the catalytic zinc. It appears that the rate of binding of NAD+ is electrostatically favored with zinc-hydroxide whereas binding of NADH is faster with neutral zinc-water. The pH dependencies of catalytic efficiencies (V/EtKm) for ethanol oxidation and acetaldehyde reduction are similarly controlled by deprotonation and protonation, respectively. The substitutions make an enzyme that resembles the homologous horse liver H51Q ADH, which has Arg-47 and Gln-51 and exhibits similar pK values. In the wild-type ADHs, it appears that His-48 (or His-51) in the proton relay systems linked to the catalytic zinc ligands modulate catalytic efficiencies.

Preparation, assay, and application of 4-fluorothreonine transaldolase from Streptomyces sp. MA37 for ß-hydroxyl amino acid derivatives.

ß-Hydroxy-α-amino acids (ßHAAs) are an essential class of building blocks of therapeutically important compounds and complex natural products. They contain two chiral centers at Cα and Cß positions, resulting in four possible diastereoisomers. Many innovative asymmetric syntheses have been developed to access structurally diverse ßHAAs. The main challenge, however, is the control of the relative and absolute stereochemistry of the asymmetric carbons in a sustainable way. In this respect, there has been considerable attention focused on the chemoenzymatic synthesis of ßHAAs via a one-step process. Nature has evolved different enzymatic routes to produce these valuable ßHAAs. Among these naturally occurring transformations, L-threonine transaldolases present potential biocatalysts to generate ßHAAs in situ. 4-Fluorothreonine transaldolase from Streptomyces sp. MA37 (FTaseMA) catalyzes the cross-over transaldolation reaction between L-Thr and fluoroacetaldehyde to give 4-fluorothreonine and acetaldehyde (Ad). It has been demonstrated that FTaseMA displays considerable substrate plasticity toward structurally diverse aldehyde acceptors, leading to the production of various ßHAAs. In this chapter, we describe methods for the preparation of FTaseMA, and the chemoenzymatic synthesis of ßHAAs from various aldehydes and L-Thr using FTaseMA.

Novel kinetic modeling of photocatalytic degradation of ethanol and acetaldehyde in air by commercial and reduced ZnO: Effect of oxygen vacancies and humidity.

A comprehensive kinetic model has been developed to address the factors and processes governing the photocatalytic removal of gaseous ethanol by using ZnO loaded in a prototype air purifier. This model simultaneously tracks the concentrations of ethanol and acetaldehyde (as its primary oxidation product) in both gas phase and on the catalyst surface. It accounts for reversible adsorption of both compounds to assign kinetic reaction parameters for different degradation pathways. The effects of oxygen vacancies on the catalyst have been validated through the comparative assessment on the catalytic performance of commercial ZnO before and after the reduction pre-treatment (10% H2/Ar gas at 500 °C). The influence of humidity has also been assessed by partitioning the concentrations of water molecules across the gas phase and catalyst surface interface. Given the significant impact of adsorption on photocatalytic processes, the beginning phases of all experiments (15 min in the dark) are integrated into the model. Results showcase a notable decrease in the adsorption removal of ethanol and acetaldehyde with an increase in relative humidity from 5% to 75%. The estimated number of active sites, as determined by the model, increases from 7.34 10-6 in commercial ZnO to 8.86 10-6 mol gcat-1 in reduced ZnO. Furthermore, the model predicts that the reaction occurs predominantly on the catalyst surface while only 14% in the gas phase. By using quantum yield calculations, the optimal humidity level for photocatalytic degradation is identified as 25% with the highest quantum yield of 6.98 10-3 (commercial ZnO) and 10.41 10-3 molecules photon-1 (reduced ZnO) catalysts.

1H NMR based sulfonation reaction kinetics of wine relevant thiols in comparison with known carbonyls.

Sulfite addition is a common tool for ensuring wines' oxidative stability via the activity of its free and weakly bound molecular fraction. As a nucleophile, bisulfite forms covalent adducts with wine's most relevant electrophiles, such as carbonyls, polyphenols, and thiols. The equilibrium in these reactions is often represented as dissociation rather than formation. Recent studies from our laboratory demonstrate, first, the acetaldehyde sulfonate dissociation, and second, the chemical stability of cysteine and epicatechin sulfonates under wine aging conditions. Thus, the objective of this study was to monitor by 1H NMR the binding specificity of known carbonyl-derived SO2 binders (acetaldehyde and pyruvic acid) in the presence of S-containing compounds (cysteine and glutathione). We report that during simulated wine aging, the sulfur dioxide that is rapidly bound to carbonyl compounds will be released and will bind to cysteine and glutathione, demonstrating the long-term sulfur dioxide binding potential of S-containing compounds. These results are meant to serve as a complement to existing literature reviews focused on molecular markers related to wines' oxidative stability and emphasize once more the importance of S-containing compounds in wine aging chemical mechanisms.

Optimized enantioselective (S)-2-hydroxypropiophenone synthesis by free- and encapsulated-resting cells of Pseudomonas putida.

BACKGROUND: Aromatic α-hydroxy ketones, such as S-2-hydroxypropiophenone (2-HPP), are highly valuable chiral building blocks useful for the synthesis of various pharmaceuticals and natural products. In the present study, enantioselective synthesis of 2-HPP was investigated by free and immobilized whole cells of Pseudomonas putida ATCC 12633 starting from readily-available aldehyde substrates. Whole resting cells of P. putida, previously grown in a culture medium containing ammonium mandelate, are a source of native benzoylformate decarboxylase (BFD) activity. BFD produced by induced P. putida resting cells is a highly active biocatalyst without any further treatment in comparison with partially purified enzyme preparations. These cells can convert benzaldehyde and acetaldehyde into the acyloin compound 2-HPP by BFD-catalyzed enantioselective cross-coupling reaction. RESULTS: The reaction was carried out in the presence of exogenous benzaldehyde (20 mM) and acetaldehyde (600 mM) as substrates in 6 mL of 200 mM phosphate buffer (pH 7) for 3 h. The optimal biomass concentration was assessed to be 0.006 g dry cell weight (DCW) mL- 1. 2-HPP titer, yield and productivity using the free cells were 1.2 g L- 1, 0.56 g 2-HPP/g benzaldehyde (0.4 mol 2-HPP/mol benzaldehyde), 0.067 g 2-HPP g- 1 DCW h- 1, respectively, under optimized biotransformation conditions (30 °C, 200 rpm). Calcium alginate (CA)-polyvinyl alcohol (PVA)-boric acid (BA)-beads were used for cell entrapment. Encapsulated whole-cells were successfully employed in four consecutive cycles for 2-HPP production under aerobic conditions without any noticeable beads degradation. Moreover, there was no production of benzyl alcohol as an unwanted by-product. CONCLUSIONS: Bioconversion by whole P. putida resting cells is an efficient strategy for the production of 2-HPP and other α-hydroxyketones.

Highly Enhanced Photocatalytic NO Removal and Inhibited Peroxyacetyl Nitrate Formation in Synergistic Acetaldehyde Degradation.

The coexistence of NO and CH3CHO in the air is considered to produce secondary peroxyacetyl nitrate (PAN) under sunlight irradiation, threatening the ecological environment and public health. Herein, we provide a simple strategy for the photocatalytic removal of NO and acetaldehyde (CH3CHO) on Sr2Sb2O7. In comparison with the single removal, the nearly complete removal of NO is reached by deep oxidation to NO3- with the assistance of CH3CHO. The underlying mechanism is revealed by GC-MS, in situ DRIFTS, and density functional theory calculations. The intermediates •CH3 from CH3CHO and NO2- from NO tend to bond and further oxidize to CH3ONO2, thus promoting NO removal. CH3NO2 and CH3ONO2 are the key products instead of PAN on Sr2Sb2O7 from the synergistic degradation of NO and CH3CHO. This work brings new insights into reaction pathway regulation for promoting performance and suppressing byproducts during synergistic air pollutant removal.

Malondialdehyde trapping by food phenolics.

The reactions between malondialdehyde and 2,5-dimethylresorcinol, orcinol, olivetol, and alkylresocinols were studied in an attempt to investigate both if this lipid oxidation product is trapped by phenolics analogously to other reactive carbonyls and to elucidate the chemical structures of the produced adducts. After being formed, malondialdehyde is both partially fractionated to acetaldehyde and oligomerized into dimers and trimers. All these compounds react with phenolics producing three main kinds of derivatives: 5(or 7)-alkyl-7(or 5)-hydroxy-4-methyl-4H-chromene-3-carbaldehydes, 7-alkyl-9-hydroxy-6H-2,6-methanobenzo[d][1,3]dioxocine-5-carbaldehydes, and 4-(3-formylphenyl)-7-hydroxy-4H-chromene-3-carbaldehydes. A total of twenty-four adducts were isolated by semipreparative high-performance liquid chromatography (HPLC) and characterized by mono- and bi-dimensional nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). Reaction pathways to explain the formation of all these compounds are proposed. Obtained results show that phenolics can trap malondialdehyde producing stable derivatives. The function(s) that such derivatives can play in foods remain(s) to be elucidated.

Acetaldehyde makes a distinct mutation signature in single-stranded DNA.

Acetaldehyde (AA), a by-product of ethanol metabolism, is acutely toxic due to its ability to react with various biological molecules including DNA and proteins, which can greatly impede key processes such as replication and transcription and lead to DNA damage. As such AA is classified as a group 1 carcinogen by the International Agency for Research on Cancer (IARC). Previous in vitro studies have shown that AA generates bulky adducts on DNA, with signature guanine-centered (GG→TT) mutations. However, due to its weak mutagenicity, short chemical half-life, and the absence of powerful genetic assays, there is considerable variability in reporting the mutagenic effects of AA in vivo. Here, we used an established yeast genetic reporter system and demonstrate that AA treatment is highly mutagenic to cells and leads to strand-biased mutations on guanines (G→T) at a high frequency on single stranded DNA (ssDNA). We further demonstrate that AA-derived mutations occur through lesion bypass on ssDNA by the translesion polymerase Polζ. Finally, we describe a unique mutation signature for AA, which we then identify in several whole-genome and -exome sequenced cancers, particularly those associated with alcohol consumption. Our study proposes a key mechanism underlying carcinogenesis by acetaldehyde-mutagenesis of single-stranded DNA.

Malondialdehyde Acetaldehyde-Adduction Changes Surfactant Protein D Structure and Function.

Alcohol consumption with concurrent cigarette smoking produces malondialdehyde acetaldehyde (MAA)-adducted lung proteins. Lung surfactant protein D (SPD) supports innate immunity via bacterial aggregation and lysis, as well as by enhancing macrophage-binding and phagocytosis. MAA-adducted SPD (SPD-MAA) has negative effects on lung cilia beating, macrophage function, and epithelial cell injury repair. Because changes in SPD multimer structure are known to impact SPD function, we hypothesized that MAA-adduction changes both SPD structure and function. Purified human SPD and SPD-MAA (1 mg/mL) were resolved by gel filtration using Sephadex G-200 and protein concentration of each fraction determined by Bradford assay. Fractions were immobilized onto nitrocellulose by slot blot and assayed by Western blot using antibodies to SPD and to MAA. Binding of SPD and SPD-MAA was determined fluorometrically using GFP-labeled Streptococcus pneumoniae (GFP-SP). Anti-bacterial aggregation of GFP-SP and macrophage bacterial phagocytosis were assayed by microscopy and permeability determined by bacterial phosphatase release. Viral injury was measured as LDH release in RSV-treated airway epithelial cells. Three sizes of SPD were resolved by gel chromatography as monomeric, trimeric, and multimeric forms. SPD multimer was the most prevalent, while the majority of SPD-MAA eluted as trimer and monomer. SPD dose-dependently bound to GFP-SP, but SPD-MAA binding to bacteria was significantly reduced. SPD enhanced, but MAA adduction of SPD prevented, both aggregation and macrophage phagocytosis of GFP-SP. Likewise, SPD increased bacterial permeability while SPD-MAA did not. In the presence of RSV, BEAS-2B cell viability was enhanced by SPD, but not protected by SPD-MAA. Our results demonstrate that MAA adduction changes the quaternary structure of SPD from multimer to trimer and monomer leading to a decrease in the native anti-microbial function of SPD. These findings suggest one mechanism for increased pneumonia observed in alcohol use disorders.

The reaction of acetaldehyde, glyoxal, and ammonia to yield 2-methylimidazole: thermodynamic and kinetic analyses of the mechanism.

The most thermodynamically and kinetically favorable pathways for the formation of 2-methylimidazole (2MI) in the reaction of glyoxal and acetaldehyde with ammonia in aqueous solution have been determined. The formation of 2MI proceeds through a number of successive intermediates of acyclic and cyclic structures, and the most favorable route (thermodynamically and kinetically) for the formation of the imidazole ring is the condensation of amine intermediates, in contrast to the existing concepts of imine structures. The limiting stage is the stage of cyclization involving the intramolecular attack by the amino group of the precyclic intermediate on the carbon atom bound to the hydroxyl group with the simultaneous release of a water molecule according to the SN2 mechanism. Further stages of stepwise dehydration lead to the formation of a cyclic diazine, the intramolecular migration of the proton of the tertiary carbon atom to the nitrogen atom of which completes the formation of 2MI. Experimental studies on the effect of the order of mixing of initial reagents on the 2MI yield confirmed the quantum-chemically substantiated favorable pathway for the formation of 2MI during the interaction of amine intermediates, and also revealed that the selectivity of the 2MI formation is achieved by successive mixing of acetaldehyde with ammonia until the formation of hydroxyamine products and their further interaction with glyoxal.