Changes in D-aspartic acid and D-glutamic acid levels in the tissues and physiological fluids of mice with various D-aspartate oxidase activities

  • J Pharm Biomed Anal. 2015 Dec 10;116:47-52. doi: 10.1016/j.jpba.2015.05.013.
Hai Han  1 ,  Yurika Miyoshi  2 ,  Reiko Koga  2 ,  Masashi Mita  3 ,  Ryuichi Konno  4 ,  Kenji Hamase  5
Affiliations
  • 1. Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Jinan University College of Pharmacy, Guangzhou 510632, China.
  • 2. Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
  • 3. Shiseido Co., Ltd., 1-6-2 Higashi-shimbashi, Minato-ku, Tokyo 105-8310, Japan.
  • 4. Department of Pharmaceutical Sciences, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara 324-8501, Japan.
  • 5. Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: [email protected].
PMID: 26058797 DOI: 10.1016/j.jpba.2015.05.013
Abstract

D-Aspartic acid (D-Asp) and D-glutamic acid (D-Glu) are currently paid attention as modulators of neuronal transmission and hormonal secretion. These two D-amino acids are metabolized only by D-aspartate oxidase (DDO) in mammals. Therefore, in order to design and develop new drugs controlling the D-Asp and D-Glu amounts via regulation of the DDO activities, changes in these acidic D-amino acid amounts in various tissues are expected to be clarified in model Animals having various DDO activities. In the present study, the amounts of Asp and Glu enantiomers in 6 brain tissues, 11 peripheral tissues and 2 physiological fluids of DDO(+/+), DDO(+/-) and DDO(-/-) mice were determined using a sensitive and selective two-dimensional HPLC system. As a result, the amounts of D-Asp were drastically increased with the decrease in the DDO activity in all the tested tissues and physiological fluids. On the Other hand, the amounts of D-Glu were almost the same among the 3 strains of mice. The present results are useful for designing new drug candidates, such as DDO inhibitors, and further studies are expected.

Keywords
Chiral analysis; Two-dimensional HPLC; d-Aspartate oxidase; d-Aspartic acid; d-Glutamic acid.
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