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Title: Deuterium-labeled phylloquinone has tissue-specific conversion to menaquinone-4 among Fischer 344 male rats

Author
item RAJABI, ALA AL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item BOOTH, SARAH L. - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item PETERSON, JAMES W. - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item CHOI, SANG WOON - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item SUTTIE, JOHN W. - University Of Wisconsin
item SHEA, M. KYLA - Wake Forest School Of Medicine
item MIAO, BENCHUN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item Grusak, Michael
item FU, XUEYAN S. - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/8/2012
Publication Date: 5/1/2012
Citation: Rajabi, A., Booth, S., Peterson, J., Choi, S., Suttie, J., Shea, M., Miao, B., Grusak, M.A., Fu, X. 2012. Deuterium-labeled phylloquinone has tissue-specific conversion to menaquinone-4 among Fischer 344 male rats. Journal of Nutrition. 142(5):841-845.

Interpretive Summary: Phylloquinone (PK) is mainly dietary form of vitamin K. PK is converted into menaquinone-4 (MK-4) in specific tissues of mammals. MK-4 has unique biological roles. However, the exact mechanism by which PK is converted to MK-4, and the location of where this conversion occurs are not known. The objective of this work is using stable isotope technology to address these gaps in knowledge. The stable isotope technology is novel and widely used in nutrition metabolism. The vegetable was grown in the heavy water, so PK in the vegetable was labeled. We fed the animals with labeled vegetable in different time course. The labeled PK and labeled MK-4 were measured in animal tissues. We found that MK-4 is the preferred form of vitamin K in multiple tissues, but there appears to be a tissue-specific regulation for the conversion of PK to MK-4. These results are important in order to better understand unique physiological roles of MK-4. The results are significant because these findings have implications for the roles of dietary vitamin K in maintaining optimal health.

Technical Abstract: Phylloquinone (PK) is converted into menaquinone-4 (MK-4) via side chain removal-addition. Stable isotope use is an effective approach to identify the tissue location of this conversion, which is currently unknown. Following a 14 d PK-deficient diet, male Fischer 344 rats (8 mo; n=15) were fed 1.6 mg deuterium-labeled PK (L-PK) per kg diet for 0 (C), 1d (PK-1) and 7 d (PK-7). Both L-PK and deuterium-labeled MK-4 (L-MK-4) were detected in tissues in PK-1 and PK-7, although results varied. Whereas some tissues had an overall increase in MK-4 in response to L-PK, total brain, testes and fat MK-4 concentrations did not. In contrast, L-MK-4 concentrations increased in all three tissues. The deuterium label was found only on the L-MK-4 naphthoquinone ring, confirming the need for side chain removal for formation of MK-4. Labeled menadione (L-MD) was detected in urine and serum in PK-1 and PK-7, confirming its role as an intermediate. A Caco-2 cell monolayer model was used to study the role of the enterocytes in the conversion process. Neither MK-4 nor MD was detected in Caco-2 cells treated with PK. However, when Caco-2 cells were treated with MD, MK-4 was formed. Similarly, MK-4 was formed in response to MD-treated kidney cells. These data demonstrate that MK-4 is the predominant form of vitamin K in multiple tissues, but there appears to be a tissue-specific regulation for the conversion of PK to MK-4.