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Quantifying Reductive Amination in Nonenzymatic Amino Acid Synthesis
Robert J Mayer1, Joseph Moran1,2
1Institut de Science et d'Ingénierie Supramoléculaires (ISIS), CNRS UMR 7006, Université de Strasbourg, 8 Allée Gaspard Monge, 67000, Strasbourg, France.
Angewandte Chemie (International Ed. in English)
|September 19, 2022
Summary
Amino acid biosynthesis primarily uses reductive amination for glutamate production. Other amino acids are formed via transamination, due to differing keto acid reactivities and glutamate
Area of Science:
- Biochemistry
- Organic Chemistry
Background:
- Amino acid biosynthesis is crucial for life.
- Glutamate is uniquely synthesized via reductive amination, while other amino acids use transamination.
Purpose of the Study:
- To investigate the chemical basis for the selective use of reductive amination in amino acid biosynthesis.
- To understand why only glutamate is produced via reductive amination.
Main Methods:
- Quantified inherent reactivities of biological alpha-keto acids.
- Utilized nonenzymatic reduction and reductive amination assays.
- Employed borohydride cyanide (BH3CN-) as a model nucleophile.
Main Results:
- Demonstrated significant differences in nonenzymatic reactivity among alpha-keto acids.
- Observed reactivity order: alpha-ketoglutarate < oxaloacetate ≈ pyruvate ≪ glyoxylate.
- Showed that ammonia preferentially reacts with the least reactive Krebs cycle alpha-keto acid.
Conclusions:
- The selective synthesis of glutamate via reductive amination is governed by the inherent chemical reactivity of alpha-keto acids.
- Glutamate's position at the thermodynamic apex of transamination reactions may explain its unique synthesis pathway.
- Chemical principles dictate the initial steps in amino acid biosynthesis pathways.
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