title: d-Amino Acid Levels in Perfused Mouse Brain Tissue and Blood: A Comparative Study.
abstract: The l-enantiomer is the predominant type of amino acid in all living systems. However, d-amino acids, once thought to be "unnatural", have been found to be indigenous even in mammalian systems and increasingly appear to be functioning in essential biological and neurological roles. Both d- and l-amino acid levels in the hippocampus, cortex, and blood samples from NIH Swiss mice are reported. Perfused brain tissues were analyzed for the first time, thereby eliminating artifacts due to endogenous blood, and decreased the mouse-to-mouse variability in amino acid levels. Total amino acid levels (l- plus d-enantiomers) in brain tissue are up to 10 times higher than in blood. However, all measured d-amino acid levels in brain tissue are typically ∼10 to 2000 times higher than blood levels. There was a 13% reduction in almost all measured d-amino acid levels in the cortex compared to those in the hippocampus. There is an approximate inverse relationship between the prevalence of an amino acid and the percentage of its d-enantiomeric form. Interestingly, glutamic acid, unlike all other amino acids, had no quantifiable level of its d-antipode. The bioneurological reason for the unique and conspicuous absence/removal of this d-amino acid is yet unknown. However, results suggest that d-glutamate metabolism is likely a unidirectional process and not a cycle, as per the l-glutamate/glutamine cycle. The results suggest that there might be unreported d-amino acid racemases in mammalian brains. The regulation and function of specific other d-amino acids are discussed.
authors.affiliation: Department of Chemistry and Biochemistry, University of Texas at Arlington , Arlington, Texas 76019, United States.
authors.forename: Choyce A
authors.initials: CA
authors.lastname: Weatherly
authors.affiliation: Department of Chemistry and Biochemistry, University of Texas at Arlington , Arlington, Texas 76019, United States.
authors.forename: Siqi
authors.initials: S
authors.lastname: Du
authors.affiliation: Department of Chemistry and Biochemistry, University of Texas at Arlington , Arlington, Texas 76019, United States.
authors.forename: Curran
authors.initials: C
authors.lastname: Parpia
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine , Baltimore, Maryland 21287, United States.
authors.forename: Polan T
authors.initials: PT
authors.lastname: Santos
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine , Baltimore, Maryland 21287, United States.|Department of Molecular Microbiology and Immunology, Johns Hopkins Blomberg School of Public Health , Baltimore, Maryland 21205, United States.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Hartman
authors.affiliation: Department of Chemistry and Biochemistry, University of Texas at Arlington , Arlington, Texas 76019, United States.
authors.forename: Daniel W
authors.identifier: 0000-0003-0501-6231
authors.initials: DW
authors.lastname: Armstrong
mesh_terms: D000596:Amino Acids / Q000032:analysis / Q000737:chemistry*; D000818:Animals; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D051379:Mice; D013237:Stereoisomerism
chemical_list: D000596:Amino Acids
keywords: blood; cortex; d-Amino acid levels; d-amino acid regulation; hippocampus; perfused brain tissue