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

• Published in: The Journal of nutrition Vol. 142; no. 5; p. 841
• Main Authors: Al Rajabi, Ala, Booth, Sarah L, Peterson, James W, Choi, Sang Woon, Suttie, John W, Shea, M Kyla, Miao, Benchun, Grusak, Michael A, Fu, Xueyan
• Format: Journal Article
• Language: English
• Published: United States 01-05-2012
• Subjects: Animal Feed; Animals; Brassica; Caco-2 Cells; Creatinine - urine; Deuterium; Enterocytes - cytology; Enterocytes - metabolism; HEK293 Cells; Humans; Liver - cytology; Male; Proteinuria - urine; Rats; Rats, Inbred F344; Tissue Distribution - physiology; Vitamin K 1 - chemistry; Vitamin K 1 - pharmacokinetics; Vitamin K 2 - analogs & derivatives; Vitamin K 2 - chemistry; Vitamin K 2 - metabolism; Vitamins - chemistry; Vitamins - pharmacokinetics
• ISSN: 1541-6100
• DOI: 10.3945/jn.111.155804

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 (control), 1 d (PK-1d), and 7 d (PK-7d). Both L-PK and deuterium-labeled MK-4 (L-MK-4) were detected in tissues in PK-1d and PK-7d, although the 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 3 tissues. The deuterium label was found only on the L-MK-4 naphthoquinone ring, confirming the need for side chain removal for the formation of MK-4. Labeled menadione (MD) was detected in urine and serum in PK-1d and PK-7d, 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 293T kidney cells, but not HuH7 liver 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.