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Cited by 33Chemical Reaction MechanismsAmino Acid Enzymes and MetabolismOrigins and Evolution of Life

Quantifying Reductive Amination in Nonenzymatic Amino Acid Synthesis

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Mayer, Robert J., Moran, Joseph·2022·Angewandte Chemie International Edition
DOI 10.1002/anie.202212237PMC PMC9828492
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Abstract

Amino acid biosynthesis initiates with the reductive amination of α‐ketoglutarate with ammonia to produce glutamate. However, the other α‐keto acids derived from the glyoxylate and Krebs cycles are converted into amino acids by transamination, rather than by reductive amination. Why is only one amino acid synthesized by reductive amination and not the others? To explore this question, we quantified the inherent reactivities of keto acids in nonenzymatic reduction and reductive amination by using BH 3 CN− as a model nucleophile. Biological α‐keto acids were found to show pronounced nonenzymatic reactivity differences for the formation of amino acids (α‐ketoglutarate<oxaloacetate≈pyruvate≪glyoxylate). Accordingly, the flow of ammonia passes through the least reactive α‐keto acid of the Krebs cycle. One possible explanation for this choice is the position of the corresponding amino acid, glutamate, at the top of the thermodynamic landscape for subsequent transamination reactions.

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  • These amino acids could be generated through transamination or reductive amination from the corresponding α-ketoacids.

    “These amino acids could be generated through transamination51 or reductive amination113 from the corresponding α-ketoacids.”

    From The protometabolic nature of prebiotic chemistry (2023) · cites this paper as [113]

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Authors
Mayer, R. J., & Moran, J.
Affiliations
Centre National de la Recherche Scientifique (FR)
Corresponding author
  • Mayer, Robert J.
  • Moran, Joseph
ORCID
Venue
Angewandte Chemie International Edition
Publisher
Wiley
Published
2022-10-21
Volume
61
Issue
48
Pages
e202212237-e202212237
ISSN
  • 1433-7851 (ISSN-L)
  • 1521-3773
DOI
10.1002/anie.202212237
PMC
PMC9828492
OpenAlex
W4296309265
Cited by
33
References
2
Citations by year
2026: 3 · 2025: 7 · 2024: 11 · 2023: 10 · 2022: 2
FWCI
2.85
Type
journal article
Language
en
Open access
Licence
Locations
  • Angewandte Chemie International Edition (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
Funders
  • HORIZON EUROPE European Research Council (101001752)
  • Volkswagen Foundation (96_742)
  • Deutsche Forschungsgemeinschaft (MA 9687/1-1)
Topics
  • Physical Sciences › Chemistry › Organic Chemistry › Chemical Reaction Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
  • Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
Keywords
reductive amination, α-keto acids, alpha-ketoglutarate, glutamate synthesis, transamination, amino acid biosynthesis
MeSH terms
Amination, Amines, Amino Acids, Ammonia, Keto Acids, Ketoglutaric Acids, Glutamic Acid

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