Presence and origin of large amounts of D-proline in the urine of mutant mice lacking D-amino acid oxidase activity.
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.
Hamase
Kenji
K
Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812 8582, Japan.
Takagi
Sayaka
S
Morikawa
Akiko
A
Konno
Ryuichi
R
Niwa
Akira
A
Zaitsu
Kiyoshi
K
D000367:Age Factors; D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics / Q000652:urine*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003605:D-Amino-Acid Oxidase / Q000172:deficiency* / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity; D011392:Proline / Q000097:blood / Q000737:chemistry* / Q000652:urine*; D013237:Stereoisomerism
D011392:Proline; D003605:D-Amino-Acid Oxidase