Comparison of the vitamins K1, K2 and K3 as cofactors for the hepatic vitamin K-dependent carboxylase

Buitenhuis, Herman C.; Soute, Berry A.M.; Vermeer, Cees

doi:10.1016/0304-4165(90)90072-5

Cited by 95 publications

(69 citation statements)

References 9 publications

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“…The K m of the wild-type FLAG-CBX for vitamin KH 2 , determined at 3.6 mM FLEEL and 16 M proFIX18, is 73.7 Ϯ 14.0 M (Table VI). This is within the range of K m values of 10 -100 M previously reported (8,32,33). The four mutants, CBX234/235, CBX359/ 360/361, CBX406/408, and CBX513/515, have similar K m values to that of the wild-type enzyme.…”

Section: Flag-cbxsupporting

confidence: 87%

Profactor IX Propeptide and Glutamate Substrate Binding Sites on the Vitamin K-dependent Carboxylase Identified by Site-directed Mutagenesis

Sugiura

Furie

Walsh

et al. 1996

Journal of Biological Chemistry

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The vitamin K-dependent carboxylase, a constituent of the endoplasmic reticulum membrane, catalyzes the conversion of reduced vitamin K to vitamin K epoxide and the concomitant conversion of glutamic acid to ␥-carboxyglutamic acid. To study structure-function relationships in the enzyme, seventeen clusters of charged residues of the bovine ␥-glutamyl carboxylase were substituted with alanines using site-specific mutagenesis. Wild-type and mutant carboxylase species were expressed in Chinese hamster ovary cells with an immunodetectable octapeptide inserted at their amino-terminal ends. Out of 17 mutant carboxylase species that contain a total of 41 charged residue to alanine substitutions, K217A/K218A (CBX217/218), R234A/H235A (CBX234/235), R359A/H360A/K361A (CBX359/360/361), R406A/H408A (CBX406/408), and R513A/K515A (CBX513/ 515) had impaired carboxylase activity compared with the wild-type enzyme. The vitamin K epoxidase activities of these mutants were reduced in parallel with the carboxylase activities. CBX217/218 appears to be inactive. High propeptide concentrations were required for stimulation of carboxylation of FLEEL by CBX234/235, CBX406/408, and CBX513/515, suggesting defects in the propeptide binding site. CBX359/360/361 showed normal affinity for the propeptide, FLEEL, proPT28, and vitamin K hydroquinone but exhibited a low catalytic rate for carboxylation. These results suggest that residue 217, residue 218, or both are either critical for catalysis or for maintaining the structure of a catalytically active enzyme. Regions around residues 234, 406, and 513 define in part the propeptide binding site, while the regions around residue 359 are involved in catalysis.Vitamin K-dependent ␥-glutamyl carboxylase is a membrane-associated endoplasmic reticulum resident enzyme that catalyzes the posttranslational conversion of specific glutamic acids of the vitamin K-dependent proteins to Gla. The vitamin K-dependent blood-clotting and regulatory proteins have clusters of 9 -12 Gla residues near their N termini. A Ca 2ϩ

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Section: Flag-cbxsupporting

confidence: 87%

Profactor IX Propeptide and Glutamate Substrate Binding Sites on the Vitamin K-dependent Carboxylase Identified by Site-directed Mutagenesis

Sugiura

Furie

Walsh

et al. 1996

Journal of Biological Chemistry

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“…The mechanism underlying this observation may be MK-7's much longer half-life time in the circulation and its reported 6-fold higher cofactor activity in vitro. 21 Despite their different lipophylicity, maximal serum concentrations of K 1 and MK-7 were seen at approximately 4 hours after intake, followed by a steep decline. A marked difference was observed during the second phase (between 8 and 96 h after mealtime), in which K 1 declined to its baseline level within several hours, whereas MK-7 remained detectable for at least 4 days (which was the last point of measurement).…”

Section: Discussionmentioning

confidence: 99%

Vitamin K–containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7

Schurgers

Teunissen

Hamulyák

et al. 2006

Blood

342

321

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Vitamin K is a cofactor in the production of blood coagulation factors (in the liver), osteocalcin (in bone), and matrix Gla protein (cartilage and vessel wall). Accumulating evidence suggests that for optimal bone and vascular health, relatively high intakes of vitamin K are required. The synthetic short-chain vitamin K 1 is commonly used in food supplements, but recently the natural long-chain menaquinone-7 (MK-7) has also become available as an over-the-counter (OTC) supplement. The purpose of this paper was to compare in healthy volunteers the absorption and efficacy of K 1 and MK-7. Serum vitamin K species were used as a marker for absorption and osteocalcin carboxylation as a marker for activity. Both K 1 and MK-7 were absorbed well, with peak serum concentrations at 4 hours after intake. A major difference between the 2 vitamin K species is the very long half-life time of MK-7, resulting in much more stable serum levels, and accumulation of MK-7 to higher levels (7-to 8-fold) during prolonged intake. MK-7 induced more complete carboxylation of osteocalcin, and hematologists should be aware that preparations supplying 50 g/d or more of MK-7 may interfere with oral anticoagulant treatment in a clinically relevant way.

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“…There are several possible reasons for this divergence in activity between the naphthoquinone homologues. However, menadione is known to be inert as a co-factor for the vitamin Kdependent gamma-carboxylation reaction [72], suggesting that alternative mechanisms, related to their redox properties, rather than protein modification are likely to be more dominant.…”

Section: Menadione and Inhibition Of Inflammationmentioning

confidence: 99%

Anti-Inflammatory Actions of Vitamin K

Hodges¹,

Pitsillides²,

Ytrebø³

et al. 2017

Vitamin K2 - Vital for Health and Wellbeing

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Naphthoquinone compounds have received attention for their ability to regulate diseases from bacterial and parasite infections through to chronic human diseases. Inflammation is widely considered to be at the root of many chronic diseases. The reports of anti-inflammatory activity of naphthoquinones, including vitamin K1 (phylloquinone) and vitamin K2s (menaquinones), are of interest due to their very low toxicity. Most of the evidence for the anti-inflammatory mechanisms of vitamin K suggests a role in the inhibition of the cell signalling complex nuclear factor kappa-B (NF-κB).

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Comparison of the vitamins K1, K2 and K3 as cofactors for the hepatic vitamin K-dependent carboxylase

Cited by 95 publications

References 9 publications

Profactor IX Propeptide and Glutamate Substrate Binding Sites on the Vitamin K-dependent Carboxylase Identified by Site-directed Mutagenesis

Profactor IX Propeptide and Glutamate Substrate Binding Sites on the Vitamin K-dependent Carboxylase Identified by Site-directed Mutagenesis

Vitamin K–containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7

Anti-Inflammatory Actions of Vitamin K

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