Dicoumarol-induced prothrombins containing 6, 7, and 8 gamma-carboxyglutamic acid residues: isolation and characterization.

Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire
O P Malhotra

Abstract

Isolation and characterization of gamma-carboxyglutamic acid (Gla) deficient prothrombins induced by Warfarin or dicoumarol are useful for studying the role of specific Gla residues in prothrombin. In addition to 7-Gla prothrombin, we have isolated two more atypical prothrombins from the barium citrate eluate, one containing 6.11, and the other, 7.85 Gla residues, presumably 6- and 8-Gla prothrombins. The actual Gla content of the 7-Gla isomer was 7.05. Each of the 6-, 7-, and 8-Gla variants showed a single component by agar or dodecyl sulfate polyacrylamide gel electrophoresis. When agar gel electrophoresis was performed in calcium, each of the variants moved more rapidly than normal (10-Gla) prothrombin. In the presence of EDTA, the 8-Gla isomer exhibited the fastest mobility, equivalent to that of normal prothrombin, followed by 7-, and then 6-Gla variants. The physiological activities of the isomers were found to be 18 to 23% for 8-, 6 to 8% for 7-, and 2 to 3% of normal prothrombin for 6-Gla variant. Prothrombin fragment 1, derived from 8-Gla prothrombin, exhibited 23% of calcium-induced fluorescence quenching, compared with 40% for 10-Gla and 8% or less for 7- and 6-Gla fragments 1. Competition radioimmunoassay data show ...Continue Reading

Citations

Jun 27, 1991·The New England Journal of Medicine·J Hirsh
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Jul 1, 1990·Baillière's Clinical Haematology·E G BovillK G Mann
Jan 11, 2005·Hematology/oncology Clinics of North America·Graham F Pineo, Russell D Hull
Dec 1, 2004·JPEN. Journal of Parenteral and Enteral Nutrition·Murray Bern

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