title: Deuterium-labeled phylloquinone has tissue-specific conversion to menaquinone-4 among Fischer 344 male rats.
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 (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.
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
authors.forename: Ala
authors.initials: A
authors.lastname: Al Rajabi
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Booth
authors.forename: James W
authors.initials: JW
authors.lastname: Peterson
authors.forename: Sang Woon
authors.initials: SW
authors.lastname: Choi
authors.forename: John W
authors.initials: JW
authors.lastname: Suttie
authors.forename: M Kyla
authors.initials: MK
authors.lastname: Shea
authors.forename: Benchun
authors.initials: B
authors.lastname: Miao
authors.forename: Michael A
authors.initials: MA
authors.lastname: Grusak
authors.forename: Xueyan
authors.initials: X
authors.lastname: Fu
mesh_terms: D000821:Animal Feed; D000818:Animals; D001937:Brassica; D018938:Caco-2 Cells; D003404:Creatinine / Q000652:urine; D003903:Deuterium; D020895:Enterocytes / Q000166:cytology / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008099:Liver / Q000166:cytology; D008297:Male; D011507:Proteinuria / Q000652:urine; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution / Q000502:physiology; D010837:Vitamin K 1 / Q000737:chemistry / Q000493:pharmacokinetics*; D024482:Vitamin K 2 / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D014815:Vitamins / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D014815:Vitamins; D024482:Vitamin K 2; C030814:menatetrenone; D010837:Vitamin K 1; D003903:Deuterium; D003404:Creatinine