d-Leucine: Evaluation in an epilepsy model

Holden, Kylie; Hartman, Adam L.

doi:10.1016/j.yebeh.2017.09.003

Cited by 8 publications

(6 citation statements)

References 57 publications

(72 reference statements)

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“…D-Leucine is an understudied amino-acid which until recently had had no known activity in eukaryotic cells [ 19 , 52 , 53 , 54 ]. In spite of this, it has long been known that D-leucine is tightly regulated in the brain by DAAO [ 52 ], and that it is present in food and produced by bacteria [ 52 , 53 ].…”

Section: Neuroactive D-isomers Without Direct Nmda Receptor Interamentioning

confidence: 99%

“…In spite of this, it has long been known that D-leucine is tightly regulated in the brain by DAAO [ 52 ], and that it is present in food and produced by bacteria [ 52 , 53 ]. Recently, it has been found that D-leucine is a potent anti-seizure drug that works against induced seizures but fails to prevent chronic epileptic seizures [ 19 , 122 ]. This seems to be because D-leucine is metabolized too quickly in the brain [ 52 ].…”

Section: Neuroactive D-isomers Without Direct Nmda Receptor Interamentioning

confidence: 99%

“…This was a good candidate due to previous work showing that other ligands of this receptor have anti-seizure properties [ 122 ]. However, TAS1R2/R3 knockout mice were found to be partially protected from induced seizures [ 19 ], suggesting a more complex role for this receptor and that the anti-seizure effects of D-leucine act through a yet undiscovered receptor in the mammalian brain.…”

Section: Neuroactive D-isomers Without Direct Nmda Receptor Interamentioning

confidence: 99%

“…These are the most studied amino acids, and they are focused on a number of well-established disease models such as Alzheimer’s disease and schizophrenia [ 15 ]. The second are D-amino acids, which have NMDA receptor independent activities in the brain [ 18 , 19 , 20 , 21 , 22 ]. In many cases, these effects have only been recently discovered and they work through no unified mechanism or disease model [ 19 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…The second are D-amino acids, which have NMDA receptor independent activities in the brain [ 18 , 19 , 20 , 21 , 22 ]. In many cases, these effects have only been recently discovered and they work through no unified mechanism or disease model [ 19 , 21 , 22 ]. Finally, the third group consists of D-amino acids that are inert within the brain but have interesting derivative molecules or metabolites in the brain [ 23 , 24 , 25 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Advances in D-Amino Acids in Neurological Research

Seckler

Lewis

2020

IJMS

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D-amino acids have been known to exist in the human brain for nearly 40 years, and they continue to be a field of active study to today. This review article aims to give a concise overview of the recent advances in D-amino acid research as they relate to the brain and neurological disorders. This work has largely been focused on modulation of the N-methyl-D-aspartate (NMDA) receptor and its relationship to Alzheimer’s disease and Schizophrenia, but there has been a wealth of novel research which has elucidated a novel role for several D-amino acids in altering brain chemistry in a neuroprotective manner. D-amino acids which have no currently known activity in the brain but which have active derivatives will also be reviewed.

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Section: Neuroactive D-isomers Without Direct Nmda Receptor Interamentioning

confidence: 99%

Section: Neuroactive D-isomers Without Direct Nmda Receptor Interamentioning

confidence: 99%

Section: Neuroactive D-isomers Without Direct Nmda Receptor Interamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Advances in D-Amino Acids in Neurological Research

Seckler

Lewis

2020

IJMS

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Synthesis of L‐[5‐¹¹C]Leucine and L‐α‐[5‐¹¹C]Methylleucine via Pd⁰‐mediated ¹¹C‐Methylation and Microfluidic Hydrogenation: Potentiality of Leucine PET Probes for Tumor Imaging

Takatani

Tahara

Tsuji³

et al. 2021

ChemMedChem

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The efficient synthesis of L-[5-11 C]leucine and L-α-[5-11 C] methylleucine has been investigated using a continuous twostep sequence of rapid reactions consisting of Pd 0 -mediated 11 C-methylation and microfluidic hydrogenation. The synthesis of L-[5-11 C]leucine and L-α-[5-11 C]methylleucine was accomplished within 40 min with a decay-corrected radiochemical yield of 15-38 % based on [ 11 C]CH 3 I, radiochemical purity of 95-99 %, and chemical purity of 95-99 %. The Pd impurities in the injectable solution measured using inductively coupled plasma mass spectrometry met the international criteria for human use. Positron emission tomography scanning after an intravenous injection of L-[5-11 C]leucine or L-α-[5-11 C]methyl leucine in A431 tumor-bearing mice was performed. As a result, L-α-[5-11 C] methylleucine was found to be a potentially useful probe for visualizing the tumor. Tissue distribution analysis showed that the accumulation value of L-α-[5-11 C]methylleucine in tumor tissue was high [12 � 3% injected dose/g tissue (%ID/g)].

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Variations of l- and d-amino acid levels in the brain of wild-type and mutant mice lacking d-amino acid oxidase activity

Wang

Weatherly

et al. 2018

Anal Bioanal Chem

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D-amino acids are now recognized to be widely present in organisms and play essential roles in biological processes. Some D-amino acids are metabolized by D-amino acid oxidase (DAO), while D-Asp and D-Glu are metabolized by D-aspartate oxidase (DDO). In this study, levels of 22 amino acids and the enantiomeric compositions of the 19 chiral proteogenic entities have been determined in the whole brain of wild-type ddY mice (ddY/DAO), mutant mice lacking DAO activity (ddY/DAO), and the heterozygous mice (ddY/DAO) using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). No significant differences were observed for L-amino acid levels among the three strains except for L-Trp which was markedly elevated in the DAO and DAO mice. The question arises as to whether this is an unknown effect of DAO inactivity. The three highest levels of L-amino acids were L-Glu, L-Asp, and L-Gln in all the three strains. The lowest L-amino acid level was L-Cys in ddY/DAO and ddY/DAO mice, while L-Trp showed the lowest level in ddY/DAOmice. The highest concentration of D-amino acid was found to be D-Ser, which also had the highest % D value (~ 25%). D-Glu had the lowest % D value (~ 0.01%) in all the three strains. Significant differences of D-Leu, D-Ala, D-Ser, D-Arg, and D-Ile were observed in ddY/DAO and ddY/DAO mice compared to ddY/DAO mice. This work provides the most complete baseline analysis of L- and D-amino acids in the brains of ddY/DAO, ddY/DAO, and ddY/DAO mice yet reported. It also provides the most effective and efficient analytical approach for measuring these analytes in biological samples. This study provides fundamental information on the role of DAO in the brain and may be relevant for future development involving novel drugs for DAO regulation.

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d-Leucine: Evaluation in an epilepsy model

Cited by 8 publications

References 57 publications

Advances in D-Amino Acids in Neurological Research

Advances in D-Amino Acids in Neurological Research

Synthesis of L‐[5‐¹¹C]Leucine and L‐α‐[5‐¹¹C]Methylleucine via Pd⁰‐mediated ¹¹C‐Methylation and Microfluidic Hydrogenation: Potentiality of Leucine PET Probes for Tumor Imaging

Variations of l- and d-amino acid levels in the brain of wild-type and mutant mice lacking d-amino acid oxidase activity

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d-Leucine: Evaluation in an epilepsy model

Cited by 8 publications

References 57 publications

Advances in D-Amino Acids in Neurological Research

Advances in D-Amino Acids in Neurological Research

Synthesis of L‐[5‐11C]Leucine and L‐α‐[5‐11C]Methylleucine via Pd0‐mediated 11C‐Methylation and Microfluidic Hydrogenation: Potentiality of Leucine PET Probes for Tumor Imaging

Variations of l- and d-amino acid levels in the brain of wild-type and mutant mice lacking d-amino acid oxidase activity

Contact Info

Product

Resources

About

Synthesis of L‐[5‐¹¹C]Leucine and L‐α‐[5‐¹¹C]Methylleucine via Pd⁰‐mediated ¹¹C‐Methylation and Microfluidic Hydrogenation: Potentiality of Leucine PET Probes for Tumor Imaging