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Kaori Yasuda, Mariko Endo, Saki Komata, Shinichi Ikushiro, Masaki Kama ...
Article type: Article
2014 Volume 88 Issue 9 Pages
451-457
Published: September 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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It is commonly known that vitamin D is initially metabolized to 25-hydroxyvitamin D (25(OH)D) in the liver, and then 25(OH)D is metabolized to a functionally active form, 1α,25-dihydroxyvitamin D (1α,25(OH)_2D), in the kidney. CYP2R1 is known to be a physiologically important vitamin D 25-hydroxylase in humans. In this study, we examined production of 25-hydroxyvitamin D_2 (25(OH)D_2) using recombinant yeast cells expressing human CYP2R1. When either vitamin D_3 (VD_3) or vitamin D_2 (VD_2) was added to the cell suspension of the CYP2R1-expressing yeast cells in a buffer containing glucose and 3-hydroxyrpropyl-β-cyclodextrin, the corresponding 25-hydroxylated product was detected. However, the conversion ratio was insufficient, which was probably due to a low efficiency of uptake of the substrate by yeast cells. To overcome this problem, we tried to examine the production of 25(OH)D_2 by a novel method using UV irradiation. When the suspension of the CYP2R1-expressing yeast cells in a buffer containing glucose was irradiated with UVB and then incubated at 37℃, 25(OH)D_2 was produced without VD_2 addition. This 25(OH)D_2 production could be due to the conversion of endogenous ergosterol to VD_2 by UV irradiation and thermal isomerization with the consequent conversion of the resulting VD_2 to 25(OH)D_2 by CYP2R1. Expectedly, the productivity of 25(OH)D_2 with this novel method was higher than that with the method to add VD_2 to the cell suspension.
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[in Japanese]
Article type: Article
2014 Volume 88 Issue 9 Pages
458-
Published: September 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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Kenji Fukui, Taisuke Wakamatsu, Yoshihiro Agari, Ryoji Masui, Seiki Ku ...
Article type: Article
2014 Volume 88 Issue 9 Pages
459-461
Published: September 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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Tohru Yoshimura, Tomokazu Ito
Article type: Article
2014 Volume 88 Issue 9 Pages
462-468
Published: September 25, 2014
Released on J-STAGE: August 10, 2017
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Because of the physiological importance of D-serine, the synthesis and degradation of D-serine have attracted interest. In mammals, D-serine is synthesized from L-serine by a eukaryotic serine racemase (SR), a member of the fold-type II group of pyridoxal 5'-phosphate (PLP)-dependent enzymes. SR structurally differs from the bacterial amino acid racemases belonging to the fold-type III PLP enzymes. In addition to racemization, SR catalyzes the serine dehydration to yield pyruvate and ammonia with the rate being comparable to that of the senile racemization. In mammals, D-serine is degraded to hydroxypyruvate and ammonia by a flavin-dependent D-amino acid oxidase. Except for mammals, D-serine dehydratase (Dsd), a fold-type III PLP enzyme, is probably responsible for the D-serine degradation. Dsds are widely distributed in various eukaryotic organisms except for mammals such as yeasts, molds, fishes, reptiles, and birds as well as in various bacterial species. The Dsd reaction depends on Zn^<2+> in addition to PLP, which is the characteristic feature of Dsd. We here introduce the enzymatic properties of SR and Dsd, and show our recent findings about their reaction mechanisms.
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Masumi Katane, Hiroshi Homma
Article type: Article
2014 Volume 88 Issue 9 Pages
469-477
Published: September 25, 2014
Released on J-STAGE: August 10, 2017
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D-Amino acid oxidase (DAO) and D-aspartate oxidase (DDO) are FAD-containing flavoproteins that catalyze the oxidative deamination of D-amino acids, including D-serine, D-alanine and D-aspartate, which are a potential coagonist or agonist of the N-methyl-D-aspartate (NMDA) receptor. Dysfunction of NMDA receptor-mediated neurotransmission has been implicated in the onset of various mental disorders such as schizophrenia. These findings may allow us to think that DAO and DDO inhibitors that can be expected to activate NMDA receptor function by augmenting the brain levels of D-serine, D-alanine and/or D-aspartate become new antipsychotic drugs in the treatment of schizophrenia. Therefore, we have tried to search and identify novel DAO and DDO inhibitors based on screening of manifold biologically active compounds of microbial origin and pre-existing drugs, or in silico screening of a large number of compounds. Herein, we review our recent studies on the compounds identified as DAO or DDO inhibitors.
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Minako Kobayashi, Ayami Sato, Ryosuke Sugahara, Masako Ota, Tomohiro Y ...
Article type: Article
2014 Volume 88 Issue 9 Pages
478-480
Published: September 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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[in Japanese], [in Japanese], [in Japanese], [in Japanese], [in Japane ...
Article type: Article
2014 Volume 88 Issue 9 Pages
481-482
Published: September 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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[in Japanese], [in Japanese], [in Japanese]
Article type: Article
2014 Volume 88 Issue 9 Pages
482-484
Published: September 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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[in Japanese], [in Japanese], [in Japanese], [in Japanese]
Article type: Article
2014 Volume 88 Issue 9 Pages
484-
Published: September 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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[in Japanese], [in Japanese]
Article type: Article
2014 Volume 88 Issue 9 Pages
485-
Published: September 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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[in Japanese], [in Japanese], [in Japanese], [in Japanese], [in Japane ...
Article type: Article
2014 Volume 88 Issue 9 Pages
486-
Published: September 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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[in Japanese]
Article type: Article
2014 Volume 88 Issue 9 Pages
486-487
Published: September 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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[in Japanese]
Article type: Article
2014 Volume 88 Issue 9 Pages
487-488
Published: September 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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[in Japanese], [in Japanese]
Article type: Article
2014 Volume 88 Issue 9 Pages
488-489
Published: September 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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[in Japanese]
Article type: Article
2014 Volume 88 Issue 9 Pages
489-490
Published: September 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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[in Japanese]
Article type: Article
2014 Volume 88 Issue 9 Pages
490-491
Published: September 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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[in Japanese]
Article type: Article
2014 Volume 88 Issue 9 Pages
492-
Published: September 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
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[in Japanese], [in Japanese], [in Japanese], [in Japanese], [in Japane ...
Article type: Article
2014 Volume 88 Issue 9 Pages
493-
Published: September 25, 2014
Released on J-STAGE: August 10, 2017
JOURNAL
FREE ACCESS