Quantifying Reductive Amination in Nonenzymatic Amino Acid Synthesis

Amino acid biosynthesis initiates with the reductive amination of alpha-ketoglutarate with ammonia to produce glutamate. However, the other alpha-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 BH3CN- as a model nucleophile. Biological alpha-keto acids were found to show pronounced nonenzymatic reactivity differences for the formation of amino acids (alpha-ketoglutarate

Automated summary

Only one alpha-keto acid is synthesized into an amino acid via reductive amination, while others are converted by transamination. The reactivity differences of keto acids in nonenzymatic reduction and reductive amination were quantified using BH3CN- as a model nucleophile, revealing pronounced differences among biological alpha-keto acids in the formation of amino acids.