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Presence and origin of large amounts of d-proline in the urine of mutant mice lacking d-amino acid oxidase activity

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Abstract

Using a column-switching HPLC system combining a micro-ODS column and a chiral column, the amounts of d-proline (d-Pro) have been determined in 18 tissues, plasma and urine of mice. To avoid the enzymatic degradation of d-amino acids in vivo, a mutant mouse strain lacking d-amino acid oxidase activity (ddY/DAO− mouse) was used. In the brain, relatively large amounts of d-Pro were observed in the anterior pituitary, posterior pituitary and pineal glands. In the peripheral tissues, the amounts of d-Pro were high in the pancreas and kidney. Above all, it is surprising that the ddY/DAO− mice excreted large amounts of d-Pro in their urine (433 nmol/mL, 20 times that of l-Pro). The origin of d-Pro has also been investigated. By comparing germ-free mice and gnotobiotic mice, intestinal bacteria were shown to have no effect on the urinary d-Pro amount. Concerning the dietary origin, a notable amount of d-Pro was still excreted in the urine after starvation for 4 days, suggesting that some of the d-Pro is produced in the mice. Age-dependent changes in the urinary d-Pro amount have also been investigated from the postnatal 1st month up to 12 months, and ddY/DAO− mice were found to excrete large amounts of d-Pro in the urine constantly throughout their lives.

Kenji Hamase is Associate Professor in the Department of Bioanalytical Chemistry, Graduate School of Pharmaceutical Sciences at Kyushu University. His current research interests focus on the development of analytical methods for d-amino acids and the study of their physiological functions and diagnostic values. He received the Japanese Society for Analytical Chemistry Award for Young Scientists in 2003, and the PSJ Award for Young Scientists in 2006.

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Acknowledgements

The authors thank Drs. Mizutani, Ozaki and Oowada, RIKEN, for the collection of urine from the germ-free and gnotobiotic ddY/DAO− mice. This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, Takeda Science Foundation, and Industrial Technology Research Grant Program in ’05 from New Energy and Industrial Technology Development Organization (NEDO) of Japan.

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Authors and Affiliations

  1. Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812 8582, Japan

    Kenji Hamase, Sayaka Takagi, Akiko Morikawa & Kiyoshi Zaitsu

  2. Department of Microbiology, Dokkyo Medical University, Mibu, Tochigi, 321 0293, Japan

    Ryuichi Konno

  3. Center for Medical Science, International University of Health and Welfare, Ohtawara, Tochigi, 324 8501, Japan

    Akira Niwa

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  1. Kenji Hamase
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  2. Sayaka Takagi
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  3. Akiko Morikawa
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  4. Ryuichi Konno
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  5. Akira Niwa
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  6. Kiyoshi Zaitsu
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Correspondence to Kiyoshi Zaitsu.

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Hamase, K., Takagi, S., Morikawa, A. et al. Presence and origin of large amounts of d-proline in the urine of mutant mice lacking d-amino acid oxidase activity. Anal Bioanal Chem 386, 705–711 (2006). https://doi.org/10.1007/s00216-006-0594-z

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