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.

Investigating brain d‐serine: Advocacy for good practices

“…However, current RgDAAO-based biosensors also detect most neutral D-AAs, including D-alanine, and might non-specifically oxidize other unexpected biological substances. Although D-alanine levels in the brain and in particular the hippocampus are much lower than those of D-serine, 29,31,32 the maximal activity and the catalytic efficiency of RgDAAO for D-alanine is 1.7-and 30 times higher than those for D-serine, 54 so it is conceivable that DAAO-based biosensors could also detect trace amounts of D-alanine which is also known to act as a co-agonist for NMDARs. Finally, it is also important to note that the commercial RgDAAO based biosensors are also sensitive to dopamine or to a series of structurally related agonists/antagonists of D1-and D2-like receptors (G. Dallerac & J.-P. Mothet, personal communication).…”

Simultaneous Determination of Concentration and Enantiomeric Composition of Amino Acids in Aqueous Solution by Using a Tetrabromobinaphthyl Dialdehyde Probe

“…[1][2][3] They also serve as important synthons andc hirality sourcesf or diversef unctional organic molecules. [1][2][3] They also serve as important synthons andc hirality sourcesf or diversef unctional organic molecules.…”

The Chain of Chirality Transfer as Determinant of Brain Functional Laterality. Breaking the Chirality Silence: Search for New Generation of Biomarkers; Relevance to Neurodegenerative Diseases, Cognitive Psychology, and Nutrition Science

“…VI Phospholipids and cholesterol both contain chiral carbon atoms and could themselves mediate stereoselective effects [35]. VII Brain tightly regulates the balance between the levels of right-and left-handed amino acids for proper structure of functional proteins [22,36,37]. VIII It is essential to know that homochirality is always relative (not absolute).…”

“…In particular, the molecular chirality is a sensitive indicator of both: the proper protein folding and pathological aggregation. Accordingly, the chirality patterns (raging from molecular chirality to the laterality of brain function) should be considered as a new generation of the biomarkers in the spectrum of the disease conditions including neurodegenerative and psychiatric disorders [22,244] Several recently published essential papers provide the broad review of the previous and current hypothesis of a perceptual and cognitive development in health [245], and pathology [246]. Referring to the limited progress in the current models, and the low efficiency of drug treatment, authors frequently appeal to the necessity of a new approach in the research of the cognitive functions mechanism.…”