biostudies-literatureMayer RJEuropean Research CouncilDeutsche ForschungsgemeinschaftVolkswagen Foundatione202212237https://www.ebi.ac.uk/biostudies/studies/S-EPMC9828492biostudies-literatureUnknown61(48)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 BH₃ 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-kAngewandte Chemie (International ed. in English)Quantifying Reductive Amination in Nonenzymatic Amino Acid Synthesis.PMC9828492101001752MA 9687/1-196_742Mayer RJMoran JfalseQuantifying Reductive Amination in Nonenzymatic Amino Acid Synthesis.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 BH₃ 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-k2022-01-01T00:00:00Z2022 Nov2026-03-27T15:39:57.668Z2025-04-05T17:02:52.762ZS-EPMC98284923612119810.1002/anie.202212237