Vitamin K – mehr als nur Koagulation

Zusammenfassung

Seit der ersten Beschreibung von Vitamin K vor knapp 80 Jahren als „Koagulationsvitamin“ werden zunehmend weitere Funktionen beschrieben. Das als Kofaktor der Gamma-Carboxylierung dienende Vitamin modifiziert verschiedene Proteine, die nicht nur in der Leber, sondern auch im Knochen und in Blutgefäßwänden vorkommen. Gegenstand der aktuellen Forschung sind mögliche protektive Wirkungen auf die Gefäßkalzifikation, fördernde Einflüsse auf die Knochendichte oder Knochenfestigkeit sowie eine hemmende Wirkung auf das Krebszellwachstum. Ferner werden weitere mögliche Einflüsse auf den Energiemetabolismus und Diabetes untersucht.

Schlüsselwörter

Kalzifikation - Warfarin - Antikoagulation - Vitamin K

• Literatur

• 1 Dam H. The antihaemorrhagic vitamin of the chick. Biochem J 1935; 29: 1273-1285
• 2 Sato T, Yamada Y, Ohtani Y et al. Production of Menaquinone (vitamin K2)-7 by Bacillus subtilis. J Biosci Bioeng 2001; 91: 16-20
• 3 Schurgers LJ, Vermeer C. Determination of phylloquinone and menaquinones in food. Effect of food matrix on circulating vitamin K concentrations. Haemostasis 2000; 30: 298-307
• 4 Shearer MJ, Newman P. Metabolism and cell biology of vitamin K. Thromb Haemost 2008; 100: 530-547
• 5 Suhara Y, Wada A, Tachibana Y et al. Structure-activity relationships in the conversion of vitamin K analogues into menaquinone-4. Substrates essential to the synthesis of menaquinone-4 in cultured human cell lines. Bioorg Med Chem 2010; 18: 3116-3124
• 6 Krasinski SD, Russell RM, Furie BC et al. The prevalence of vitamin K deficiency in chronic gastrointestinal disorders. Am J Clin Nutr 1985; 41: 639-643
• 7 Stafford DW. The vitamin K cycle. J Thromb Haemost 2005; 3: 1873-1878
• 8 Furie B, Furie BC. The molecular basis of blood coagulation. Cell 1988; 53: 505-518
• 9 Vermeer C. Gamma-carboxyglutamate-containing proteins and the vitamin K-dependent carboxylase. Biochem J 1990; 266: 625-636
• 10 Thijssen HH, Drittij-Reijnders MJ. Vitamin K distribution in rat tissues: dietary phylloquinone is a source of tissue menaquinone-4. Br J Nutr 1994; 72: 415-425
• 11 Price PA, Urist MR, Otawara Y. Matrix Gla Protein, a new y-carboxyglutamic acid-containing protein which is associated with the organic matrix of bone. Biochem Biophys Res Commun 1983; 117: 765-771
• 12 Shanahan CM, Cary NR B, Metcalfe JC, Weissberg PL. High expression of genes for calcification-regulating proteins in human atherosclerotic plaques. J Clin Invest 1994; 93: 2393-2402
• 13 Schurgers LJ, Spronk HM, Skepper JN et al. Post-translational modifications regulate matrix Gla protein function: importance for inhibition of vascular smooth muscle cell calcification. J Thromb Haemost 2007; 5: 2503-2511
• 14 Rennenberg R, Kessels A, Schurgers LJ et al. Vascular calcifications as a marker of increased cardiovascular risk: A meta-analysis. Vasc Health Risk Manag 2009; 5: 185-197
• 15 Schlieper G, Westenfeld R, Krüger T et al. Circulating nonphosphorylated carboxylated matrix gla protein predicts survival in ESRD. J Am Soc Nephrol 2011; 22: 387-395
• 16 Cranenburg EC, Brandenburg VM, Vermeer C et al. Uncarboxylated matrix Gla protein (ucMGP) is associated with coronary artery calcification in haemodialysis patients. Thromb Haemost 2009; 101: 359-366
• 17 Westenfeld R, Krüger T, Schlieper G et al. Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: a randomized trial. Am J Kidney Dis 2012; 59: 186-195
• 18 Angelillo-Scherrer A, Garcia de Frutos P, Aparicio C et al. Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis. Nature 2001; 7: 215-221
• 19 Son BK, Kozaki K, Iijima K et al. Statins protect human aortic smooth muscle cells from inorganic phosphate-induced calcification by restoring Gas6-Axl survival pathway. Circ Res 2006; 98: 1024-1031
• 20 Apalset EM, Gjesdal CG, Eide GE, Tell GS. Intake of vitamin K1 and K2 and risk of hip fractures: The Hordaland Health Study. Bone 2011; 49: 990-995
• 21 Feskanich D, Weber P, Willett WC et al. Vitamin K intake and hip fractures in women: a prospective study. Am J Clin Nutr 1999; 69: 74-79
• 22 Iwamoto J, Seki A, Sato Y, Matsumoto H. Vitamin K2 improves renal function and increases femoral bone strength in rats with renal insufficiency. Calcif Tissue Int 2012; 90: 50-59
• 23 Lee NK, Sowa H, Hinoi E et al. Endocrine regulation of energy metabolism by the skeleton. Cell 2007; 130: 456-469
• 24 Pollock NK, Bernard PJ, Gower BA et al. Lower uncarboxylated osteocalcin concentrations in children with prediabetes is associated with beta-cell function. J Clin Endocrinol Metab 2011; 96: E1092-E1099
• 25 Nimptsch K, Rohrmann S, Kaaks R, Linseisen J. Dietary vitamin K intake in relation to cancer incidence and mortality: results from the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg). Am J Clin Nutr 2010; 91: 1348-1358
• 26 Mamede AC, Tavares SD, Abrantes AM et al. The role of vitamins in cancer: a review. Nutr Cancer 2011; 63: 479-494
• 27 Verrax J, Delvaux M, Beghein N et al. Enhancement of quinone redox cycling by ascorbate induces a caspase-3 independent cell death in human leukaemia cells. An in vitro comparative study Free Radical Res 2005; 39: 649-657
• 28 Sasaki R, Suzuki Y, Yonezawa Y et al. DNA polymerase-c inhibition by vitamin K3 induces mitochondria-mediated cytotoxicity in human cancer cells. Cancer Sci 2008; 99: 1040-1048
• 29 Price PA, Faus SA, Williamson MK. Warfarin causes rapid calcification of the elastic lamellae in rat arteries and heart valves. Arterioscler Thromb Vasc Biol 1998; 18: 1400-1407
• 30 Schurgers LJ, Spronk HM, Soute BA et al. Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats. Blood 2007; 109: 2823-2831
• 31 Weijs B, Blaauw Y, Rennenberg R et al. Patients using vitamin K antagonists show increased levels of coronary calcification: an observational study in low-risk atrial fibrillation patients. Eur Heart J 2011; 32: 2555-2562
• 32 Bundesinstitut für Risikobewertung. Zimt und Cumarin: eine Klarstellung aus wissenschaftlich-behördlicher Sicht. Deutsche Lebensmittel-Rundschau 2007; 103: 480-487
• 33 Chen NX, Moe SM. Vascular calcification: pathophysiology and risk factors. Curr Hypertens Rep 2012; 14: 228-237
• 34 Krüger T, Brandenburg V, Schlieper G et al. Sailing between Scylla and Charybdis: oral long-term anticoagulation in dialysis patients. Nephrol Dial Transplant 2013; 28: 534-541
• 35 Shea MK, O’Donnell CJ, Vermeer C et al. Circulating uncarboxylated matrix Gla protein is associated with vitamin K nutritional status, but not coronary artery calcium, in older adults. J Nutr 2011; 141: 1529-1534
• 36 Vermeer C, Shearer MJ, Zittermann A et al. Beyond deficiency: potential benefits of increased intakes of vitamin K for bone and vascular health. Eur J Nutr 2004; 43: 325-335