vitamin-k-semiquinone-radical and dihydrophylloquinone

The physiological function and putative health roles of vitamin K-dependent proteins now extend beyond their classical role in hemostasis and include bone mineralization, arterial calcification, apoptosis, phagocytosis, growth control, chemotaxis, and signal transduction. Current assessments of vitamin K status do not reflect the variety of molecular forms of vitamin K. We assessed whether urinary excretion of 2-methyl-3-(5'-carboxy-3'-methyl-2'-pentenyl)-1,4-naphthoquinone (7C-aglycone) and 2-methyl-3-(3'-3'-carboxymethylpropyl)-1,4-naphthoquinone (5C-aglycone), vitamin K metabolites common to both phylloquinone and the menaquinone series, reflect dietary vitamin K intake. In a randomized crossover study, 9 adults resided in a metabolic unit for two 30-d periods separated by a free-living period of > or = 4 wk. During each residency, subjects consumed 3 sequential diets: a control diet (93 microg phylloquinone/d) for 5 d, a phylloquinone-restricted diet (11 microg/d) for 15 d, followed by a randomly assigned repletion diet for 10 d with either phylloquinone (206 microg/d) or dihydrophylloquinone (240 microg/d). During the second residency, the alternative repletion diet was assigned. Urinary excretion of the 5C- and 7C-aglycones was measured in sequential 24-h collections. The 5C-aglycone accounted for approximately 75% of total excretion and declined in response to phylloquinone restriction (P = 0.001) to approximately 30% of that during the control diet period. Repletion with phylloquinone and dihydrophylloquinone doubled the excretion rate of the major 5C-aglycone by 24 h (P < 0.001), and tripled excretion by 4 d. There was a linear relationship between the logarithm of total urinary excretion and dietary vitamin K intake (r = 0.699, P < 0.001). We conclude that the urinary excretion of vitamin K metabolites reflects dietary phylloquinone intake and offers the first candidate marker of global vitamin K status.

Topics: Adult; Diet; Female; Humans; Male; Molecular Structure; Vitamin K; Vitamin K 1

Dysregulation of myelin sulfatides is a risk factor for cognitive decline with age. Vitamin K is present in high concentrations in the brain and has been implicated in the regulation of sulfatide metabolism. Our objective was to investigate the age-related interrelation between dietary vitamin K and sulfatides in myelin fractions isolated from the brain regions of Fischer 344 male rats fed one of two dietary forms of vitamin K: phylloquinone or its hydrogenated form, 2',3'-dihydrophylloquinone (dK), for 28 days. Both dietary forms of vitamin K were converted to menaquinone-4 (MK-4) in the brain. The efficiency of dietary dK conversion to MK-4 compared to dietary phylloquinone was lower in the striatum and cortex, and was similar to that in the hippocampus. There were significant positive correlations between sulfatides and MK-4 in the hippocampus (phylloquinone-supplemented diet, 12 and 24 months; dK-supplemented diet, 12 months) and cortex (phylloquinone-supplemented diet, 12 and 24 months). No significant correlations were observed in the striatum. Furthermore, sulfatides in the hippocampus were significantly positively correlated with MK-4 in serum. This is the first attempt to establish and characterize a novel animal model that exploits the inability of dietary dK to convert to brain MK-4 to study the dietary effects of vitamin K on brain sulfatide in brain regions controlling motor and cognitive functions. Our findings suggest that this animal model may be useful for investigation of the effect of the dietary vitamin K on sulfatide metabolism, myelin structure and behavior functions.

Topics: Age Factors; Animals; Brain; Diet; Dietary Supplements; Male; Models, Animal; Myelin Sheath; Rats; Rats, Inbred F344; Sulfoglycosphingolipids; Vitamin K; Vitamin K 1; Vitamin K 2

Phylloquinone is converted into menaquinone-4 and accumulates in extrahepatic tissues. Neither the route nor the function of the conversion is known. One possible metabolic route might be the release of menadione from phylloquinone by catabolic activity. In the present study we explored the presence of menadione in urine and the effect of vitamin K intake on its excretion. Menadione in urine was analysed by HPLC assay with fluorescence detection. Urine from healthy male volunteers was collected before and after administration of a single dose of K vitamins. Basal menadione excretion in non-supplemented subjects (n 6) was 5.4 (sd 3.2) microg/d. Urinary menadione excretion increased greatly after oral intake of the K vitamins, phylloquinone and menaquinone-4 and -7. This effect was apparent within 1-2 h and peaked at about 3 h after intake. Amounts of menadione excreted in 24 h after vitamin K intake ranged, on a molar basis, from 1 to 5 % of the administered dose, indicating that about 5-25 % of the ingested K vitamins had been catabolized to menadione. Menadione excretion was not enhanced by phylloquinone administered subcutaneously or by 2',3'-dihydrophylloquinone administered orally. In archived samples from a depletion/repletion study (Booth et al. (2001) Am J Clin Nutr 74, 783-790), urinary menadione excretion mirrored dietary phylloquinone intake. The present study shows that menadione is a catabolic product of K vitamins formed after oral intake. The rapid appearance in urine after oral but not subcutaneous administration suggests that catabolism occurs during intestinal absorption. The observations make it likely that part of the menaquinone-4 in tissues results from uptake and prenylation of circulating menadione.

Topics: Administration, Cutaneous; Administration, Oral; Cell Line; Cells, Cultured; Dietary Supplements; Hemostatics; Humans; Male; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K 3; Vitamins