Conversion of Dietary Phylloquinone to Tissue Menaquinone-4 in Rats is Not Dependent on Gut Bacteria

Abstract

The ability of male rats to accumulate menaquinone-4 (MK-4) in tissues when fed a vitamin K-deficient diet supplemented with intraperitoneal phylloquinone (K) as the sole source of vitamin K for 14 d was assessed. In both conventionally housed controls and gnotobiotic rats, supplementation with the equivalent of 1500 microg vitamin K/kg diet increased (P < 0.001) tissue MK-4 concentrations above those of controls fed a vitamin K-deficient diet. MK-4 concentrations were approximately 5 ng/g (11 pmol/g) in liver, 14 ng/g in heart, 17 ng/g in kidney, 50 ng/g in brain and 250 ng/g in mandibular salivary glands of gnotobiotic rats. MK-4 concentrations in conventionally housed rats were higher than in gnotobiotic rats in heart (P < 0.01), brain (P < 0.01) and kidney (P < 0.05) but lower in salivary gland (P < 0.05). Cultures of a kidney-derived cell line (293) converted K to the expoxide of MK-4 in a manner that was dependent on both time of incubation and concentration of vitamin K in the media. A liver-derived cell line (H-35) was less active in carrying out this conversion. These data offer conclusive proof that the tissue-specific formation of MK-4 from K is a metabolic transformation that does not require bacterial transformation to menadione as an intermediate in the process.

Warfarin-induced impairment of cortical bone material quality and compensatory adaptation of cortical bone structure to mechanical stimuli

“…75 mg/kg per week), which resulted in the blood coagulation status within clinical therapeutic range, reduced intrinsic material, and biomechanical properties in femoral mid-shaft cortical bones of approximately 6-months old rats (Simon et al 2002). Marked decrease in bone osteocalcin content but no apparent skeletal changes in rats treated with high-dose warfarin plus vitamin K 1 (Price & Williamson 1981) would be also compatible with our findings, because vitamin K 1 can be endogenously converted to menaquinone-4, a vitamin K 2 with four isoprenoid residues (Davidson et al 1998, Ronden et al 1998, and menaquinone-4 has been recently suggested to improve bone material quality independently of osteocalcin (Ichikawa et al 2006, Sugiyama 2007. In contrast, however, warfarin monotherapy effectively decreased osteocalcin content in bone but did not alter skeletal status in young adult rats (Haffa et al 2000).…”

Anti-Inflammatory Actions of Vitamin K

“…Research that started in the 1990s demonstrated that menadione was an important derivative from vitamin K1 that was converted in the rat to make the vitamin K2 congener menaquinone-4 [64][65][66][67]. The enzyme responsible for the conversion of menadione to menaquinone-4, UBIAD1 [68] has a wide distribution across species and likely plays a significant role in the vitamin K status of many animals (see chapter by O'Neil et al, this volume).…”

Effects of the blood coagulation vitamin K as an inhibitor of arterial calcification

“…It is now confirmed by different research groups that the essential nutritional form of vitamin K, vitamin K 1 , derived from plants is, to different extents, converted to menaquinone-4 (MK4) in various extrahepatic tissues (14)(15)(16). In the brain the conversion is almost 100% (17) and Spronk et al (16) have shown a significant conversion in the aortic wall.…”