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Vitamin K: The coagulation vitamin that became omnipotent.Thromb
Haemost. 2007; 98 (1):120-5.
Vitamin K,
discovered in the 1930s, functions as cofactor for the
posttranslational carboxylation of glutamate residues. Gammacarboxy
glutamic acid (Gla)-residues were first identified in prothrombin and
coagulation factors in the 1970s; subsequently, extra-hepatic Gla
proteins were described, including osteocalcin and matrix Gla protein
(MGP). Impairment of the function of osteocalcin and MGP due to
incomplete carboxylation results in an increased risk for developing
osteoporosis and vascular calcification, respectively, and is an
unexpected side effect of treatment with oral anticoagulants. It is
conceivable that other side effects, possible involving
growth-arrest-specific gene 6 (Gas6) protein will be identified in
forthcoming years. In healthy individuals, substantial fractions of
osteocalcin and MGP circulate as incompletely carboxylated species,
indicating that the majority of these individuals is subclinically
vitamin K-deficient. Potential new application areas for vitamin K are
therefore its use in dietary supplements and functional foods for
healthy individuals to prevent bone and vascular disease, as well as
for patients on oral anticoagulant treatment to offer them protection
against coumarin-induced side effects and to reduce diet-induced
fluctuations in their INR values.
Role of vitamin K and vitamin K-dependent proteins in vascular
calcification.Z
Kardiol. 2001;90 Suppl 3:57-63.
OBJECTIVES: To
provide a rational basis for recommended daily allowances (RDA) of
dietary phylloquinone (vitamin K1) and menaquinone (vitamin K2) intake
that adequately supply extrahepatic (notably vascular) tissue
requirements. BACKGROUND: Vitamin K has a key function in the
synthesis of at least two proteins involved in calcium and bone
metabolism, namely osteocalcin and matrix Gla-protein (MGP). MGP was
shown to be a strong inhibitor of vascular calcification. Present RDA
values for vitamin K are based on the hepatic phylloquinone
requirement for coagulation factor synthesis. Accumulating data
suggest that extrahepatic tissues such as bone and vessel wall require
higher dietary intakes and have a preference for menaquinone rather
than for phylloquinone. METHODS: Tissue-specific vitamin K consumption
under controlled intake was determined in warfarin-treated rats using
the vitamin K-quinone/epoxide ratio as a measure for vitamin K
consumption. Immunohistochemical analysis of human vascular material
was performed using a monoclonal antibody against MGP. The same
antibody was used for quantification of MGP levels in serum. RESULTS:
At least some extrahepatic tissues including the arterial vessel wall
have a high preference for accumulating and using menaquinone rather
than phylloquinone. Both intima and media sclerosis are associated
with high tissue concentrations of MGP, with the most prominent
accumulation at the interface between vascular tissue and calcified
material. This was consistent with increased concentrations of
circulating MGP in subjects with atherosclerosis and diabetes
mellitus. CONCLUSIONS: This is the first report demonstrating the
association between MGP and vascular calcification. The hypothesis is
put forward that undercarboxylation of MGP is a risk factor for
vascular calcification and that the present RDA values are too low to
ensure full carboxylation of MGP.
Vitamin K: biochemistry, function, and deficiency. Review.Invest
Clin. 1998;39(3):213-29.
Vitamin K is a
cofactor for the synthesis of blood coagulation Factors II, VII, IX
and X, and inhibitors such as Protein C and S and bone matrix protein.
Its active form is a coenzyme in the glutamic acid carboxylation.
Vitamin K-dependent factors form enzymatic complexes with calcium and
membrane phospholipids. The insufficiency of gamma glutamic
carboxylation impairs the hemostatic function. Hereditary
deficiencies, antibiotics and oral anticoagulants, decrease the
capacity of complex formation giving way to hemorrhage or thrombosis,
or bone mass disturbances which are easily treated with administration
of Vitamin K. The main causes of Vitamin K deficiency are lack of
hepatic storage in newborns, liver insufficiency, malabsorption,
dietetic deficiency, therapy with the antibiotics and coumarin
administration. For the study of Vitamin K there are methods to
measure the Vit K dependent proteins and as well methods to measure
specifically the quinonas.
Vitamin K
nutrition and osteoporosis.
J Nutr. 1995;125(7):1812-21.
Although
the abundance of vitamin K-dependent proteins in bone suggests an
important function, the precise role of vitamin K in skeletal health
remains to be determined. Serum concentrations of vitamin K are
reportedly reduced in older individuals and persons with osteoporotic
fracture. Whether this is causally related to vitamin K insufficiency
or simply reflects inadequate nutritional status is unclear.
Circulating levels of undercarboxylated osteocalcin may be a sensitive
marker of vitamin K inadequacy and have been reported to be increased
in both postmenopausal women and individuals who sustained hip
fracture. It is also possible that vitamin K indirectly affects the
skeleton via control of renal calcium excretion. The effect of vitamin
K antagonists (oral anticoagulants) on both renal calcium excretion
and bone density is controversial. Thus, many of the reports
implicating a role for vitamin K insufficiency in the development of
osteoporosis are conflicting. This review summarizes current knowledge
regarding a possible role of vitamin K insufficiency in the
pathogenesis of osteoporosis.
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