Relationship between Structure and Biological Activity of Various Vitamin K Forms

Vitamin K is involved many biological processes, such as the regulation of blood coagulation, prevention of vascular calcification, bone metabolism and modulation of cell proliferation. Menaquinones (MK) and phylloquinone vary in biological activity, showing different bioavailability, half-life and transport mechanisms. Vitamin K1 and MK-4 remain present in the plasma for 8–24 h, whereas long-chain menaquinones can be detected up to 96 h after administration. Geometric structure is also an important factor that conditions their properties. Cis-phylloquinone shows nearly no biological activity. An equivalent study for menaquinone is not available. The effective dose to decrease uncarboxylated osteocalcin was six times lower for MK-7 than for MK-4. Similarly, MK-7 affected blood coagulation system at dose three to four times lower than vitamin K1. Both vitamin K1 and MK-7 inhibited the decline in bone mineral density, however benefits for the occurrence of cardiovascular diseases have been observed only for long-chain menaquinones. There are currently no guidelines for the recommended doses and forms of vitamin K in the prevention of osteoporosis, atherosclerosis and other cardiovascular disorders. Due to the presence of isomers with unknown biological properties in some dietary supplements, quality and safety of that products may be questioned.

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The effect of vitamin K1 supplementation for 12 months on bone mineral density and indices of vitamin K status and bone turnover in adult Crohn's disease patients

Proceedings of The Nutrition Society ◽

10.1017/s0029665111001248 ◽

2011 ◽

Vol 70 (OCE3) ◽

Author(s):

E. M. O'Connor ◽

G. Grealy ◽

J. McCarthy ◽

A. Desmond ◽

O. Craig ◽

...

Keyword(s):

Bone Mineral Density ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Bone Turnover ◽

Bone Mineral ◽

Vitamin K ◽

Vitamin K1 ◽

Mineral Density

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MK-7 and Its Effects on Bone Quality and Strength

Nutrients ◽

10.3390/nu12040965 ◽

2020 ◽

Vol 12 (4) ◽

pp. 965 ◽

Cited By ~ 3

Author(s):

Toshiro Sato ◽

Naoko Inaba ◽

Takatoshi Yamashita

Keyword(s):

Bone Mineral Density ◽

Bone Quality ◽

Vitamin K ◽

Half Life ◽

Daily Intake ◽

Vitamin K2 ◽

Matrix Gla Protein ◽

Vitamin K1 ◽

Mineral Density ◽

The Matrix

Vitamin K acts as a cofactor and is required for post-translational γ-carboxylation of vitamin K-dependent proteins (VKDP). The current recommended daily intake (RDI) of vitamin K in most countries has been established based on normal coagulation requirements. Vitamin K1 and menaquinone (MK)-4 has been shown to decrease osteocalcin (OC) γ-carboxylation at RDI levels. Among the several vitamin K homologs, only MK-7 (vitamin K2) can promote γ-carboxylation of extrahepatic VKDPs, OC, and the matrix Gla protein at a nutritional dose around RDI. MK-7 has higher efficacy due to its higher bioavailability and longer half-life than other vitamin K homologs. As vitamin K1, MK-4, and MK-7 have distinct bioactivities, their RDIs should be established based on their relative activities. MK-7 increases bone mineral density and promotes bone quality and strength. Collagen production, and thus, bone quality may be affected by MK-7 or MK-4 converted from MK-7. In this review, we comprehensively discuss the various properties of MK-7.

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Vitamin K and bone health

Proceedings of The Nutrition Society ◽

10.1079/pns2003305 ◽

2003 ◽

Vol 62 (4) ◽

pp. 839-843 ◽

Cited By ~ 42

Author(s):

Susanne Bügel

Keyword(s):

Bone Mineral Density ◽

Bone Formation ◽

Bone Mineral ◽

Vitamin K ◽

Bone Health ◽

Coagulation System ◽

Dietary Vitamin ◽

Undercarboxylated Osteocalcin ◽

Mineral Density ◽

Low Bone Mineral Density

Vitamin K, originally recognised as a factor required for normal blood coagulation, is now receiving more attention in relation to its role in bone metabolism. Vitamin K is a coenzyme for glutamate carboxylase, which mediates the conversion of glutamate to γ-carboxyglutamate (Gla). Gla residues attract Ca2+ and incorporate these ions into the hydroxyapatite crystals. There are at least three Gla proteins associated with bone tissue, of which osteocalcin is the most abundant and best known. Osteocalcin is the major non-collagenous protein incorporated in bone matrix during bone formation. However, approximately 30% of the newly-produced osteocalcin stays in the circulation where it may be used as an indicator of bone formation. Vitamin K deficiency results in an increase in undercarboxylated osteocalcin, a protein with low biological activity. Several studies have demonstrated that low dietary vitamin K intake is associated with low bone mineral density or increased fractures. Additionally, vitamin K supplementation has been shown to reduce undercarboxylated osteocalcin and improve the bone turnover profile. Some studies have indicated that high levels of undercarboxylated osteocalcin (as a result of low vitamin K intake?) are associated with low bone mineral density and increased hip fracture. The current dietary recommendation for vitamin K is 1 μ/kg body weight per d, based on saturation of the coagulation system. The daily dietary vitamin K intake is estimated to be in the range 124–375 μg/d in a European population. Thus, a deficiency based on the hepatic coagulation system would be unusual, but recent data suggest that the requirement in relation to bone health might be higher.

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Comparison of vitamin K1 and K2 kinetics of vitamin K epoxide reductase C1

Hämostaseologie ◽

10.1055/s-0037-1621632 ◽

2008 ◽

Vol 28 (S 01) ◽

pp. S106-S106

Author(s):

P. Westhofen ◽

M. Watzka ◽

M. Hass ◽

C. Müller-Reible ◽

D. Lütjohann ◽

...

Keyword(s):

Vitamin K ◽

Vitamin K1 ◽

Vitamin K Epoxide Reductase ◽

Epoxide Reductase ◽

Kinetics Of

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Placental Transfer of Vitamin K1 and Its Implications in Fetal Hemostasis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647631 ◽

1988 ◽

Vol 60 (01) ◽

pp. 039-043 ◽

Cited By ~ 52

Author(s):

L Mandelbrot ◽

M Guillaumont ◽

M Leclercq ◽

J J Lefrère ◽

D Gozin ◽

...

Keyword(s):

Vitamin K ◽

High Performance ◽

Ultrasound Guidance ◽

Placental Transfer ◽

Vitamin K1 ◽

Vitamin K Deficiency ◽

Prothrombin Activity ◽

Oral Supplementation ◽

K Deficiency ◽

The Mean

SummaryVitamin K status was evaluated using coagulation studies and/ or vitamin IQ assays in a total of 53 normal fetuses and 47 neonates. Second trimester fetal blood samples were obtained for prenatal diagnosis under ultrasound guidance. Endogenous vitamin K1 concentrations (determined by high performance liquid chromatography) were substantially lower than maternal levels. The mean maternal-fetal gradient was 14-fold at mid trimester and 18-fold at birth. Despite low vitamin K levels, descarboxy prothrombin, detected by a staphylocoagulase assay, was elevated in only a single fetus and a single neonate.After maternal oral supplementation with vitamin K1, cord vitamin K1 levels were boosted 30-fold at mid trimester and 60 fold at term, demonstrating placental transfer. However, these levels were substantially lower than corresponding supplemented maternal levels. Despite elevated vitamin K1 concentrations, supplemented fetuses and neonates showed no increase in total or coagulant prothrombin activity. These results suggest that the low prothrombin levels found during intrauterine life are not due to vitamin K deficiency.

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A Re-Appraisal of the Role of Blood Coagulation and Platelets in the Generalized Shwartzman Phenomenon

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649455 ◽

1966 ◽

Vol 15 (03/04) ◽

pp. 519-538 ◽

Cited By ~ 10

Author(s):

J Levin ◽

E Beck

Keyword(s):

Blood Coagulation ◽

The State ◽

Coagulation System ◽

Renal Lesions ◽

Intravascular Coagulation ◽

Renal Glomeruli ◽

Coagulation Mechanism ◽

Shwartzman Phenomenon ◽

Do So

SummaryThe role of intravascular coagulation in the production of the generalized Shwartzman phenomenon has been evaluated. The administration of endotoxin to animals prepared with Thorotrast results in activation of the coagulation mechanism with the resultant deposition of fibrinoid material in the renal glomeruli. Anticoagulation prevents alterations in the state of the coagulation system and inhibits development of the renal lesions. Platelets are not primarily involved. Platelet antiserum produces similar lesions in animals prepared with Thorotrast, but appears to do so in a manner which does not significantly involve intravascular coagulation.The production of adrenal cortical hemorrhage, comparable to that seen in the Waterhouse-Friderichsen syndrome, following the administration of endotoxin to animals that had previously received ACTH does not require intravascular coagulation and may not be a manifestation of the generalized Shwartzman phenomenon.

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Dietary Vitamin and Stability of Oral Anticoagulation: Proposal of a Diet with Constant Vitamin K1 Content

Thrombosis and Haemostasis ◽

10.1055/s-0038-1655997 ◽

1997 ◽

Vol 77 (03) ◽

pp. 504-509 ◽

Cited By ~ 47

Author(s):

Sarah L Booth ◽

Jacqueline M Charnley ◽

James A Sadowski ◽

Edward Saltzman ◽

Edwin G Bovill ◽

...

Keyword(s):

Dietary Intake ◽

Vitamin K ◽

High Performance ◽

Case Reports ◽

Food Composition ◽

Dietary Guidelines ◽

Dietary Vitamin ◽

Vitamin K1 ◽

The Stability ◽

The Impact

SummaryCase reports cited in Medline or Biological Abstracts (1966-1996) were reviewed to evaluate the impact of vitamin K1 dietary intake on the stability of anticoagulant control in patients using coumarin derivatives. Reported nutrient-drug interactions cannot always be explained by the vitamin K1 content of the food items. However, metabolic data indicate that a consistent dietary intake of vitamin K is important to attain a daily equilibrium in vitamin K status. We report a diet that provides a stable intake of vitamin K1, equivalent to the current U.S. Recommended Dietary Allowance, using food composition data derived from high-performance liquid chromatography. Inconsistencies in the published literature indicate that prospective clinical studies should be undertaken to clarify the putative dietary vitamin K1-coumarin interaction. The dietary guidelines reported here may be used in such studies.

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Biological Function and Chemistry of Endothelin. A Review

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19991211 ◽

1999 ◽

Vol 64 (8) ◽

pp. 1211-1252 ◽

Cited By ~ 4

Author(s):

Jan Hlaváček ◽

Renáta Marcová

Keyword(s):

Biological Activity ◽

Amino Acid ◽

Biological Function ◽

Biological Properties ◽

Structural Basis ◽

Amino Acid Residues ◽

Snake Venoms ◽

Vasoactive Peptides ◽

Physico Chemical ◽

Endothelin A

The first part of this review deals with the biosynthesis and a biological function of strongly vasoactive peptides named endothelins (ETs) including vasoactive intestinal contractor. Where it was useful, snake venoms sarafotoxins which are structural endothelin derivatives, were also mentioned. In the second part, an attention is paid to structural basis of the ETs biological activity, with respect to alterations of amino acid residues in the parent peptides modifying the conformation and consequently the physico-chemical and biological properties in corresponding ETs analogs. Special attention is focussed on the area of ETs receptors and their interaction with peptide and non peptide agonists and antagonists, important in designing selective inhibitors of ETs receptors potentially applicable as drugs in a medicine. A review with 182 references.

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