β-(8-Quinoyl)-L-alanine

Plants catalyze the biosynthesis of a large number of non-protein amino acids, which are usually toxic for other organisms. In this review, the chemistry and metabolism of N-heterocyclic non-protein amino acids from plants are described. These N-heterocyclic non-protein amino acids are composed of β-substituted alanines and include mimosine, β-pyrazol-1-yl-L-alanine, willardiine, isowillardiine, and lathyrine. These β-substituted alanines consisted of an N-heterocyclic moiety and an alanyl side chain. This review explains how these individual moieties are derived from their precursors and how they are used as the substrate for biosynthesizing the respective N-heterocyclic non-protein amino acids. In addition, known catabolism and possible role of these non-protein amino acids in the actual host is explained.

Theoretical conformational analysis of N-formyl-L-serine-L-alanine-NH2 dipeptide model was investigated using B3LYP/6-311+G(d,p) and M06-2X/6-311+G(d,p) calculations. In this research, 243 total possible conformations of the dipeptide model were optimized including 87 stable conformers and the other disappeared ones migrated to more stable geometries. Migration pattern suggests more stability of the dipeptide model with the serine (ser) in βL, γL, and γD and the alanine (ala) in γD and γL configurations, along with 26 of the found conformers having β-turn structures. Our calculations reveal that the most stable conformer, γL+γD, is in β-turn region of Ramachandran map; therefore, serine-alanine (ser-ala) dipeptide model should be adopted with a β-turn conformation. The atoms in molecules (AIM) topological analysis was carried out to characterize the nature of the intramolecular hydrogen bonding in β-turn structures. The γL+γD, including three hydrogen bonds, has the highest stability, while αLaγL as the most unstable β-turn conformer bears two and one hydrogen bonds at the B3LYP/6-311+G(d,p) and M06-2X/6-311+G(d,p) levels of theory, respectively. Graphical abstract.

Background: Interventions that induce ketosis simultaneously lower blood glucose and the explanation for this phenomenon is unknown. Additionally, the glucose-lowering effect of acute ketosis is greater in people with type 2 diabetes (T2D). On the contrary, L-alanine is a gluconeogenic substrate secreted by skeletal muscle at higher levels in people with T2D and infusing of ketones lower circulating L-alanine blood levels. In this study, we sought to determine whether supplementation with L-alanine would attenuate the glucose-lowering effect of exogenous ketosis using a ketone ester (KE). Methods: This crossover study involved 10 healthy human volunteers who fasted for 24 h prior to the ingestion of 25 g of d-β-hydroxybutyrate (βHB) in the form of a KE drink (ΔG® ) on two separate visits. During one of the visits, participants additionally ingested 2 g of L-alanine to see whether L-alanine supplementation would attenuate the glucose-lowering effect of the KE drink. Blood L-alanine, L-glutamine, glucose, βHB, free fatty acids (FFA), lactate and C-peptide were measured for 120 min after ingestion of the KE, with or without L-alanine. Findings: The KE drinks elevated blood βHB concentrations from negligible levels to 4.52 ± 1.23 mmol/L, lowered glucose from 4.97 ± SD 0.39 to 3.77 ± SD 0.40 mmol/L, and lowered and L-alanine from 0.56 ± SD 0.88 to 0.41 ± SD 0.91 mmol/L. L-alanine in the KE drink elevated blood L-Alanine by 0.68 ± SD 0.15 mmol/L, but had no significant effect on blood βHB, L-glutamine, FFA, lactate, nor C-peptide concentrations. By contrast, L-alanine supplementation significantly attenuated the ketosis-induced drop in glucose from 28% ± SD 8% to 16% ± SD 7% (p < .01). Conclusions: The glucose-lowering effect of acutely elevated βHB is partially due to βHB decreasing L-alanine availability as a substrate for gluconeogenesis.