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DOI: 10.1055/s-0038-1642744
The In Vivo Effects of Oral Anticoagulants in Man: Comparison Between Liver and Non-Hepatic Tissues
Publication History
Received 25 June 1987
Accepted after revision 29 October 1987
Publication Date:
21 May 2018 (online)
Summary
The in vivo effects of oral anticoagulant therapy with 4–hydroxycoumarins on various vitamin K–dependent enzyme systems in man were compared. In hepatic microsomes obtained from donors who has been treated with 4–hydroxycoumarins for more than 6 months, the vitamin K 2,3 epoxide reductase activity and the DTT–dependent vitamin K quinone reductase activity were diminished to 35% and 20% of the corresponding normal values. In the non–hepatic tissues, only a small decrease in vitamin K 2,3 epoxide reductase activity could be demonstrated, while no differences were found in the vitamin K quinone reductase activities. In none of the tissues a significant increase of non–carboxylated precursor proteins was observed, whereas also vitamin K hydroquinone–dependent carboxylase activities seemed to be unaffected by the anticoagulant treatment.
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References
- 1 Suttie JW. Vitamin K-dependent carboxylase. Ann Rev Biochem 1985; 54: 459-477
- 2 Olson RE. The function and metabolism of vitamin K. Ann Rev Nutr 1984; 1985; 4: 281-337
- 3 Vermeer C, de Boer-van den Berg MA G. Vitamin K-dependent carboxylase. Haematologia 1985; 18: 71-97
- 4 Suttie JW, Preusch PC. Studies on the vitamin K-dependent carboxylase and vitamin K epoxide reductase in rat liver. Haemostasis 1986; 16: 193-215
- 5 Fasco MJ, Hildebrandt EF, Suttie JW. Evidence that warfarin anticoagulant action involves two distinct reductase activities. J Biol Chem 1982; 257: 11210-11212
- 6 Wallin R, Suttie JW. Vitamin K-dependent carboxylation and vitamin K epoxidation. Evidence that the warfarin sensitive microsomal NAD(P)H dehydrogenase reduces vitamin Kj in these reactions Biochem J 1981; 194: 983-988
- 7 Vermeer C, Hendrix H, Daemen M. Vitamin K-dependent carboxylases from non-hepatic tissues. FEBS Lett 1982; 148: 317-320
- 8 Buchtal SD, Bell RG. Vitamin K dependent carboxylation of glutamate residues to gamma-carboxyglutamate in microsomes from spleen and testes: comparison with liver, lung and kidney. Biochemistry 1983; 22: 1077-1082
- 9 de Boer-van den Berg MA G, Verstijnen CP H J, Vermeer C. Vitamin K-dependent carboxylase in skin. J Invest Dermatol 1986; 87: 377-380
- 10 Soute BA M, de Metz M, Vermeer C. Characteristics of vitamin K-dependent carboxylating systems from human liver and placenta. FEBS Lett 1982; 146: 365-368
- 11 Poser JW, Esh FS, Ling NC, Price PA. Isolation and sequence of the vitamin K dependent protein from human bone. J Biol Chem 1981; 255: 8685-8691
- 12 Soute BA M, Miiller-Esterl W, de Boer-van den Berg MA G, Ulrich M, Vermeer C. Discovery of a β-carboxyglutamic acid-containing protein in human spermatozoa. FEBS Lett 1985; 190: 137-141
- 13 de Boer-van den Berg MA G, Thijssen HH W, Vermeer C. The in vivo effects of acenocoumarol, phenprocoumon and warfarin on vitamin K dependent carboxylase in various tissues of the rat. Biochim Biophys Acta 1986; 884: 150-157
- 14 De Metz M, Soute BA M, Hemker HC, Vermeer C. Stimulation of the vitamin K-dependent carboxylase from bovine liver. Biochem J 1983; 209: 719-724
- 15 Tishler M, Freser LT, Wendler NL. Hydro, oxido and other derivatives of vitamin and related compounds. J Am Chem Soc 1940; 62: 2866-2871
- 16 Sedmak JJ, Grossberg SE. A rapid, sensitive and versatile assay for protein using Coomassie Brilliant Blue G250. Anal Biochem 1977; 79: 544-552
- 17 Van Haarlem L JM, Soute BA M, Hemker HC, Vermeer C. Vitamin K-dependent carboxylase: possible role for thioredoxin in the reduction of vitamin K-metabolites in liver. FEBS Lett 1987; 222: 353-357
- 18 Thijssen HH W, Janssen CA T, Dritty-Reynders MJ. The effect of S-warfarin administration on vitamin K-2,3 epoxide reductase activity in liver, kidney and testis of the rat. Biochem Pharmacol 1986; 35: 3277-3282