An overview on d-amino acids

Abstract

More than half a century ago researchers thought that D-amino acids had a minor function compared to L-enantiomers in biological processes. Many evidences have shown that D-amino acids are present in high concentration in microorganisms, plants, mammals and humans and fulfil specific biological functions. In the brain of mammals, D-serine (D-Ser) acts as a co-agonist of the N-methyl-D-aspartate (NMDA)-type glutamate receptors, responsible for learning, memory and behaviour. D-Ser metabolism is relevant for disorders associated with an altered function of the NMDA receptor, such as schizophrenia, ischemia, epilepsy and neurodegenerative disorders. On the other hand, D-aspartate (D-Asp) is one of the major regulators of adult neurogenesis and plays an important role in the development of endocrine function. D-Asp is present in the neuroendocrine and endocrine tissues and testes, and regulates the synthesis and secretion of hormones and spermatogenesis. Also food proteins contain D-amino acids that are naturally originated or processing-induced under conditions such as high temperatures, acid and alkali treatments and fermentation processes. The presence of D-amino acids in dairy products denotes thermal and alkaline treatments and microbial contamination. Two enzymes are involved in the metabolism of D-amino acids: amino acid racemase in the synthesis and D-amino acid oxidase in the degradation.

Amino acids and acylcarnitines as potential metabolomic markers of schizophrenia: new approaches to diagnostics and therapy

“…Ïîìèìî ýòîãî, îáíàðóaeèâàþòñÿ çíà÷èòåëüíî áîëåå âûñîêèå óðîâíè àëàíèíà, ãëèöèíà, ëåéöèíà è ôåíèëàëàíèíà â ñïèííîìîçãîâîé aeèäêîñòè ïàöèåíòîâ ñ øèçîôðåíèåé ïî ñðàâíåíèþ ñ çäîðîâûìè ëþäüìè [31]. Ïîëîaeåíèå, ÷òî íàðóøåííûé ìåòàáîëèçì D-ñåðèíà ìîaeåò ÿâëÿòüñÿ ïðåäèêòîðîì øèçîôðåíèè, íàøëî ïîäòâåðaeäåíèå è â ïîñëåäíèõ ñòàòüÿõ [32,33]. S. Saleem ñ ñîàâò.…”

Chiral Graphs: Reduced Representations of Ligand Scaffolds for Stereoselective Biomolecular Recognition, Drug Design, and Enhanced Exploration of Chemical Structure Space

“…Its relevance extends beyond the chemistry of stereoselective synthesis and chiral separation methods into biology, where natural life (as we know it) depends on molecular workhorses called proteins that are the largest chiral molecules known in nature. These biomolecules are made exclusively from l ‐amino acids, although d ‐amino acids do play specific biological roles in all domains of life . An important aspect of protein function is binding to and recognizing small endogenous ligands (or substrates) to carry out specific signaling tasks.…”

“…These biomolecules are made exclusively from l-amino acids, although d-aminoa cidsd op lay specific biological roles in all domains of life. [2] An important aspecto f protein functioni sb inding to and recognizing small endogenous ligands (or substrates) to carry out specific signaling tasks. The chirality of proteinsm akes this molecular recognition process inherently stereoselective, because most protein binding sites are chiral.…”

Lineage-specific diversification in the usage of D-glutamate and D-aspartate in early-branching metazoans

“…Life is primarily based on L-amino acids, but the growing data from different disciplines stress the recruitments and importance of D-amino acids in various signaling and structural functions at all levels of biological organization [1][2][3]. With thousands of publications, the chemical biology of D-amino acids is transforming from scattered observations during the 1960-90s [4][5][6] into a rapidly growing field with many promises for therapeutic and bioengineering [3,7]. For example, since bacteria are known sources of D-amino acids, there are specific enzymes and mechanisms, which recognize these enantiomers as a part of the immune response in mammals [8].…”