Biochemistry of D-aspartate in mammalian cells.
Recent investigations have shown that D-aspartate (D-Asp) plays an important physiological role(s) in the mammalian body. Here, several recent studies of free D-Asp metabolism in mammals, focusing on cellular localization in tissues, intracellular localization, biosynthesis, efflux, uptake and degradation are reviewed. D-Asp in mammalian tissues is present in specific cells, indicating the existence of specific molecular components that regulate D-Asp levels and localization in tissues. In the rat pheochromocytoma cell line (PC12) and its subclones, D-Asp is synthesized intracellularly, most likely by Asp racemase(s). Endogenous D-Asp apparently has two different intracellular localization patterns: cytoplasmic and vesicular. In PC12 cells, D-Asp release can occur through three distinct pathways: 1) spontaneous, continuous release of cytoplasmic D-Asp, which is not associated with a specific stimulus; 2) release of cytoplasmic D-Asp via a volume-sensitive organic anion channel that connects the cytoplasm and extracellular space; 3) exocytotic discharge of vesicular D-Asp. Under certain conditions, D-Asp can be released via a mechanism that involves the L-Glu transporter. D-Asp is thus apparently in dynamic flux at the cellular level to carry out its physiological function(s) in mammals.
Homma
H
H
Laboratory of Biomolecular Science, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan. hommah@pharm.kitasato-u.ac.jp
D000591:Amino Acid Isomerases / Q000378:metabolism; D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000818:Animals; D026603:D-Aspartic Acid / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D022142:Secretory Vesicles / Q000378:metabolism*
D027322:Amino Acid Transport System X-AG; D007473:Ion Channels; D026603:D-Aspartic Acid; D000591:Amino Acid Isomerases