Metal Ions Turn on a Stereoselective Nonenzymatic Reduction of Keto Acids by the Coenzyme NADH DOI Creative Commons
Robert J. Mayer, Joseph Moran

Published: Oct. 10, 2023

The relationship between genetic molecules and metabolism is one of the longest standing problems for origin life. A central molecule within early coenzyme nicotinamide adenine dinucleotide (NAD(H)), a modified ribonucleotide reducing agent. Yet, without enzymes, NADH does not reduce carbonyl compounds, its primary metabolic substrates, leading to an apparent paradox regarding role in evolution metabolism. We now report that abundant metal ions turn on nonenzymatic, stereoselective, potentially primordial reduction reaction keto acids by NADH. Kinetic, mechanistic, computational studies elucidate mechanism way stereochemistry transferred. Complexes metals with RNA-derived coenzymes could have mediated transition from inorganic organic agents propagation chirality

Language: Английский

NADH-mediated primordial synthesis of amino acids DOI Creative Commons
Noemí Nogal, Javier Luis‐Barrera, Sonia Vela

et al.

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(7), P. 1924 - 1932

Published: Jan. 1, 2024

Amino acid formation by hydride transfer from NADH without the need for enzymes connects prebiotic chemistry with metabolic pathways that presumably led to these biomolecules in first autotrophic protocells.

Language: Английский

Citations

9
The molecular landscape of cellular metal ion biology DOI Creative Commons
Simran Kaur Aulakh, Oliver Lemke, Łukasz Szyrwiel

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 3, 2024

Summary Metal ions play crucial roles in cells, yet the broader impact of metal availability on biological networks remains underexplored. We generated genome-wide resources, systematically quantifying yeast cell growth, metallomic, proteomic, and genetic responses upon varying each its essential (Ca, Cu, Fe, K, Mg, Mn, Mo, Na, Zn), over several orders magnitude. find that deeply cellular networks, with 57.6% proteome, including most signalling pathways, responding. While response to is distinct, our data reveals common properties responsiveness, such as concentration interdependencies homeostasis. describe a compendium metal-dependent processes reveal understudied genes can be functionally annotated based their responses. Furthermore, we report metalloenzymes occupy central nodes metabolic network are more likely encoded by isozymes, resulting system-wide responsiveness availability.

Language: Английский

Citations

3
Nonenzymatic Hydration of Phosphoenolpyruvate: General Conditions for Hydration in Protometabolism by Searching Across Pathways DOI Creative Commons

Joris Zimmermann,

Atalay Bora Basar,

Joseph Moran

et al.

Published: June 3, 2024

Numerous reactions within metabolic pathways have been reported to occur nonenzymatically, supporting the hypothesis that life began from a primitive nonenzymatic precursor metabolism. However, most of those studies reproduce individual transformations or segments without providing common set conditions for classes span multiple pathways. In this study, we search across recurring chemical transformation in metabolism: alkene hydration. The mild identify (Fe oxides such as green rust) apply all hydration rTCA cycle and gluconeogenesis, including phosphoenolpyruvate (PEP) 2-phosphoglycerate (2PGA), which had not previously under conditions. Mechanistic insights were obtained by studying analogous substrates through anoxic radical trapping experiments. Searching provides complementary strategy triangulate conducive emergence protometabolism.

Language: Английский

Citations

2
Metal Ions Turn on a Stereoselective Nonenzymatic Reduction of Keto Acids by the Coenzyme NADH DOI Creative Commons
Robert J. Mayer, Joseph Moran

Published: Oct. 10, 2023

The relationship between genetic molecules and metabolism is one of the longest standing problems for origin life. A central molecule within early coenzyme nicotinamide adenine dinucleotide (NAD(H)), a modified ribonucleotide reducing agent. Yet, without enzymes, NADH does not reduce carbonyl compounds, its primary metabolic substrates, leading to an apparent paradox regarding role in evolution metabolism. We now report that abundant metal ions turn on nonenzymatic, stereoselective, potentially primordial reduction reaction keto acids by NADH. Kinetic, mechanistic, computational studies elucidate mechanism way stereochemistry transferred. Complexes metals with RNA-derived coenzymes could have mediated transition from inorganic organic agents propagation chirality

Language: Английский

Citations

4