TY - JOUR
T1 - D -Amino Acid Levels in Perfused Mouse Brain Tissue and Blood
T2 - A Comparative Study
AU - Weatherly, Choyce A.
AU - Du, Siqi
AU - Parpia, Curran
AU - Santos, Polan T.
AU - Hartman, Adam L.
AU - Armstrong, Daniel W.
N1 - Funding Information:
This work was supported by the Robert A. Welch Foundation (Y0026; D.W.A.) and the National Institute of Neurological Disorders and Stroke (K08NS070931; A.L.H.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Health and Human Services, the United States Government, National Institute of Neurological Disorders and Stroke, or the National Institutes of Health.
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/6/21
Y1 - 2017/6/21
N2 - 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.
AB - 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.
KW - blood
KW - cortex
KW - d -Amino acid levels
KW - d -amino acid regulation
KW - hippocampus
KW - perfused brain tissue
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U2 - 10.1021/acschemneuro.6b00398
DO - 10.1021/acschemneuro.6b00398
M3 - Article
C2 - 28206740
AN - SCOPUS:85015475712
SN - 1948-7193
VL - 8
SP - 1251
EP - 1261
JO - ACS Chemical Neuroscience
JF - ACS Chemical Neuroscience
IS - 6
ER -