VITAMINS

Unique function of flavin coenzyme in type 2 isopentenyl diphosphate isomerase involved in archaeal isoprenoid biosynthesis

Hisashi Hemmi

Article type: Article
2011 Volume 85 Issue 1 Pages 1-8
Published: January 25, 2011
Released on J-STAGE: October 10, 2017

DOIhttps://doi.org/10.20632/vso.85.1_1

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Type 2 isopentenyl diphosphate isomerase is a flavoenzyme that catalyzes interconversion between isopentenyl diphosphate and dimethylallyl diphosphate, which are precursors for the biosynthesis of diverse isoprenoid compounds. The reaction mechanism of the enzyme, which requires redox coenzymes FMN and NAD(P)H for activity, attracts interest because the enzyme catalyzes isomerization, a reaction without net redox change. From our studies using type 2 isopentenyl diphosphate isomerase from a thermoacidophilic archaeon Sulfolobus shibatae, consumption of only a catalytic amount of NAD(P)H and actual requirement for reduced FMN as a coenzyme were shown. Moreover, our structural and mutagenic works on the enzyme, together with enzymological studies by other groups, revealed the unique function of the flavin coenzyme as a general acid-base catalyst without redox role.

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The development of therapeutic agents based on vitamin D and vitamin K for the treatment of cancers and osteoporosis

Kimie Nakagawa

Article type: Article
2011 Volume 85 Issue 1 Pages 9-17
Published: January 25, 2011
Released on J-STAGE: October 10, 2017

DOIhttps://doi.org/10.20632/vso.85.1_9

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1α,25-Dihydroxyvitamin D_3[1α,25(OH)_2D_3], the major regulator of calcium homeostasis, has potent antiproliferative and anti-invasive properties in vitro in cancer cells. Little information is available concerning structural motifs of the 1α,25(OH)_2D_3 molecule responsible for modulation of differentiation and apoptosis. We synthesized all possible A-ring diastereomers of the singly dehydroxylated 19-nor-1α,25(OH)_2D_3, 2-methyl-1α,25(OH)_2D_3 and its 20-epimer and evaluated their biological activities in human promyelocytic leukemia (HL-60) cells. We have clearly identified for the first time the structural motifs on the basis of the stereochemistry of both hydroxyl groups at positions 1 and 3 of the A-ring of the 1α,25(OH)_2D_3 molecule responsible for the inductions of differentiation and apoptosis of HL-60 cells. In vivo studies demonstrated that 1α,25(OH)_2D_3 slowed the progression of breast, prostate, and other carcinomas. A key question was whether 1α,25(OH)_2D_3 exerts its anticarcinogenic effects in vivo by a mechanism that is dependent on its capacity to limit the proliferation and invasiveness of cancer cells in vitro. We used metastatic Lewis lung carcinoma cells expressing green fluorescent protein (LLC-GFP cells) and examined the metastatic activity in vitamin D receptor (VDR) null mutant (VDR-/-) mice and their wild-type counterparts (VDR+/+mice). VDR-/- mice exhibited hypocalcemia and extremely high serum levels of 1α,25(OH)_2D_3. The metastatic growth of LLC-GFP cells was remarkably reduced in response to the serum levels of 1α,25(OH)_2D_3 but not to the serum levels of calcium. We showed that 1α,25(OH)_2D_3 inhibited the metastatic growth of lung cancer cells in a defined animal model. There are two forms of naturally occurring vitamin K, phylloquinone and menaquinones. Phylloquinone (vitamin K_1) is the major type (>90%) of dietary vitamin K, but its concentrations in animal tissues are remarkably low compared with those of menaquinones, especially menaquinone-4 (vitamin K_2), the major form (>90%) of vitamin K in tissues. Despite this great difference, the origin of tissue menaquinone-4 has yet to be exclusively defined. It is postulated that phylloquinone is converted into menaquinone-4 and accumulates in extrahepatic tissues. To clarify this, phylloquinone with a deuterium-labeled 2-methyl-1,4-naphthoquinone ring was given orally to mice and cerebra were collected for D NMR and LC-MS/MS analyses. We identified the labeled menaquinone-4 that was converted from the given phylloquinone. Our results may aid in the clarification of the physiological role of MK-4 in the brain and the development of new drugs for the treatment of neuronal diseases.

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The contents of B-group vitamins in various tissues, serum, and urine of vitamin B_<12>-deficient rats

Katsumi Shibata, Tetsunori Kawata, Kaori Ishida, Atsushi Shimizu, Aya ...

Article type: Article
2011 Volume 85 Issue 1 Pages 18-22
Published: January 25, 2011
Released on J-STAGE: October 10, 2017

DOIhttps://doi.org/10.20632/vso.85.1_18

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We measured the contents of B-group vitamins in the urine, serum, liver, and kidney of vitamin B_<12>-deficient rats. Urine and liver vitamin B_<12> contents in urine and liver were lower in the B_<12>-deficient rats than in the control rats. Contents of vitamin B_2, nicotinamide, and pantothenic acid in the urine, liver and kidney were not different between the B_<12>-deficient and control rats. On the other hand, contents of vitamin B_1, vitamin B_6, folate, and biotin in the urine, liver, and kidney were different between the two groups. Vitamin B_1 and folate contents in the urine, liver, and kidney were lower in the B_<12>-deficient rats than in the control rats. Vitamin B_6 content in the liver was almost equal between both groups, but, the content in urine was lower and that of kidney was higher in the B_<12>-deficinet rats than in the control rats. Biotin content in the urine and kidney was higher in the B_<12>-deficient rats, but the content in the liver was lower in the B_<12>-deficient rats.

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Structural Characterization of L-Glutamate Oxidase from Streptomyces sp. X-119-6

Jiro Arima, Chiduko Sasaki, Chika Sakaguchi, Hiroshi Mizuno, Takashi T ...

Article type: Article
2011 Volume 85 Issue 1 Pages 23-24
Published: January 25, 2011
Released on J-STAGE: October 10, 2017

DOIhttps://doi.org/10.20632/vso.85.1_23

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LXXLL peptide mimetics as inhibitors of the interaction of vitamin D recceptor with coactivators

Yusuke Mita, Yuichi Hashimoto, Minoru Ishikawa

Article type: Article
2011 Volume 85 Issue 1 Pages 25-26
Published: January 25, 2011
Released on J-STAGE: October 10, 2017

DOIhttps://doi.org/10.20632/vso.85.1_25

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Selenoproteins in response to ER stress

Takashi Tamura

Article type: Article
2011 Volume 85 Issue 1 Pages 27-28
Published: January 25, 2011
Released on J-STAGE: October 10, 2017

DOIhttps://doi.org/10.20632/vso.85.1_27

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D-aspartate as a dietary supplement

Shiro Kato, Tohru Yoshimura

Article type: Article
2011 Volume 85 Issue 1 Pages 29-30
Published: January 25, 2011
Released on J-STAGE: October 10, 2017

DOIhttps://doi.org/10.20632/vso.85.1_29

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Cytotoxic effect and signal function of reactive oxygen species : Redox regulation via ascorbate peroxidase

Takanori Maruta, Shigeru Shigeoka

Article type: Article
2011 Volume 85 Issue 1 Pages 31-33
Published: January 25, 2011
Released on J-STAGE: October 10, 2017

DOIhttps://doi.org/10.20632/vso.85.1_31

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[title in Japanese]

Article type: Bibliography
2011 Volume 85 Issue 1 Pages 34-37
Published: January 25, 2011
Released on J-STAGE: October 10, 2017

DOIhttps://doi.org/10.20632/vso.85.1_34

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