Advances in D-Amino Acids in Neurological Research

Seckler, James M.; Lewis, Stephen J.

doi:10.3390/ijms21197325

Cited by 39 publications

(34 citation statements)

References 170 publications

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“…A more detailed summary of the implications of D-Ala in hosts can be found in the recent review by Lee et al (28). While D-Glu and D-Pro are produced by the gut microbiota strains, the roles of these two D-AAs in animals remain obscure, although recent studies suggest protective roles for D-Glu against Alzheimer's Disease (57)(58)(59)(60)(61), and sedative and hypnotic effects of D-Pro in neonatal chicks (62). We also found low but non-negligible amounts of D-Ser and D-Asp (except for B. cereus) in the gut microbial strains.…”

Section: Discussionmentioning

confidence: 99%

“…We also found low but non-negligible amounts of D-Ser and D-Asp (except for B. cereus) in the gut microbial strains. The physiological roles of D-Ser and D-Asp have been extensively studied in the central nervous system (CNS) (61,63) and endocrine system (63,64). Although the biological roles of gut microbiota-derived D-Ser and D-Asp in the host are equivocal, putative functions of gut microbiota-or diet-derived D-Ser in the CNS (65,66) and acute kidney injury (67) have been reported.…”

Section: Discussionmentioning

confidence: 99%

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Profiling of D-alanine production by the microbial isolates of rat gut microbiota

Lee

Qiu

Zhang

et al. 2021

Preprint

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D-alanine (D-Ala) and several other D-amino acids (D-AAs), unusual amino acids present in mammals, act as hormones and neuromodulators in nervous and endocrine systems. Unlike the endogenously synthesized D-serine in animals, D-Ala may be from exogenous sources, e.g., diet and intestinal microorganisms. However, it is unclear if the capability to produce D-Ala and other D-AAs varies among different microbial strains in the gut. We isolated individual microorganisms of rat gut microbiota and profiled their D-AA secretion in vitro, focusing on D-Ala. Serial dilutions of intestinal content from adult male rats were plated on agar to obtain clonal cultures. Using MALDI-TOF MS for rapid strain typing, we identified 38 unique isolates, grouped into 11 species based on 16S rRNA gene sequences. We then used two-tier screening to profile bacterial D-AA secretion, combining a D-amino acid oxidase-based enzymatic assay for rapid assessment of overall D-AA amount, followed by chiral LC-MS/MS to quantify individual D-AAs, revealing 19 out of the 38 isolated strains as D-AA producers. LC-MS/MS analysis of the eight top D-AA producers showed high levels of D-Ala in all strains tested, with substantial inter- and intra-species variations. Though results from enzymatic assay and LC-MS/MS analysis aligned well, LC-MS/MS further revealed the existence of D-glutamate and D-aspartate, which are poor substrates for enzymatic assay. We observed large inter- and intra-species variation of D-AA secretion profiles from rat gut microbiome species, demonstrating the importance of chemical profiling of gut microbiota in addition to sequencing, furthering the idea that microbial metabolites modulate host physiology.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Profiling of D-alanine production by the microbial isolates of rat gut microbiota

Lee

Qiu

Zhang

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…Thus, the levels of D-amino acids and their synthesis and degradation are linked to cognitive impairment, which is the core feature of schizophrenia and Alzheimer's disease (AD). Indeed, studies show that the enzymes involved in D-amino acids metabolism correlate with AD and schizophrenia [2,3].…”

Section: Introductionmentioning

confidence: 99%

d-Amino Acids and pLG72 in Alzheimer’s Disease and Schizophrenia

Cheng

Lin

Lane

2021

IJMS

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Numerous studies over the last several years have shown that d-amino acids, especially d-serine, have been related to brain and neurological disorders. Acknowledged neurological functions of d-amino acids include neurotransmission and learning and memory functions through modulating N-methyl-d-aspartate type glutamate receptors (NMDARs). Aberrant d-amino acids level and polymorphisms of genes related to d-amino acids metabolism are associated with neurodegenerative brain conditions. This review summarizes the roles of d-amino acids and pLG72, also known as d-amino acid oxidase activator, on two neurodegenerative disorders, schizophrenia and Alzheimer’s disease (AD). The scope includes the changes in d-amino acids levels, gene polymorphisms of G72 genomics, and the role of pLG72 on NMDARs and mitochondria in schizophrenia and AD. The clinical diagnostic value of d-amino acids and pLG72 and the therapeutic importance are also reviewed.

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“…Therefore, each amino acid has two enantiomeric forms, denoted l - and d -amino acids. In mammals, although l -amino acids predominate, the d -enantiomers also exist and have biological functions in certain tissues such as the brain [ 2 ]. In particular, d -serine ( d -Ser) and d -aspartate ( d -Asp) are relatively abundant in the brain and have distinct roles from their l -enantiomers [ 3 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Measurement of Amino Acid Enantiomers in Aged Mouse Brain Samples by LC/MS/MS Combined with Derivatization Using Nα-(5-Fluoro-2,4-dinitrophenyl)-l-leucinamide (l-FDLA)

2021

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d-amino acids have distinct roles from their l-enantiomer. In particular, some d-amino acids function as agonists or antagonists of neuronal receptors and are involved in higher brain functions. Thus, it is important to precisely measure the levels of these amino acid enantiomers in cells and tissues. Various quantification methods have been developed for measurements of chiral amino acids. However, each method has advantages and disadvantages. Additionally, measuring the amino acid enantiomers in crude biological samples requires a higher selectivity. In this study, we developed a quantification method for amino acid enantiomers using derivatization with Nα-(5-Fluoro-2,4-dinitrophenyl)-l-leucinamide (l-FDLA) followed by liquid chromatography–tandem mass spectrometry (LC/MS/MS) with a conventional reversed-phase column. We simultaneously identified 10 chiral amino acids. Furthermore, we applied this method to investigate murine tissue samples and examined the effect of aging on the amino acid levels in aged brain regions. We found that aging decreased the levels of both d-serine and d-aspartate in the hippocampus. In addition, d-Phenylalanine in the thalamus significantly increased with age. In conclusion, our method is suitable for the quantification of the d-amino acids in crude biological samples and may contribute to elucidating the biological roles of chiral amino acids.

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Advances in D-Amino Acids in Neurological Research

Cited by 39 publications

References 170 publications

Profiling of D-alanine production by the microbial isolates of rat gut microbiota

Profiling of D-alanine production by the microbial isolates of rat gut microbiota

d-Amino Acids and pLG72 in Alzheimer’s Disease and Schizophrenia

Simultaneous Measurement of Amino Acid Enantiomers in Aged Mouse Brain Samples by LC/MS/MS Combined with Derivatization Using Nα-(5-Fluoro-2,4-dinitrophenyl)-l-leucinamide (l-FDLA)

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