Friedman P A, Rosenberg R D, Hauschka P V, Fitz-James A
Biochim Biophys Acta. 1977 Sep 27;494(1):271-6. doi: 10.1016/0005-2795(77)90155-6.
Prothrombin has been purified from the plasmas of normal human donors and from patients ingesting coumarins. Equimolar amounts of normal prothrombin or coumadin-induced prothrombin were incubated with phospholipid micelles in the presence of Ca2+. Subsequent gel filtration of the incubation mixtures demonstrated that all of the normal prothrombin was bound to the phospholipid; only half of the coumadin-induced prothrombin was bound. Normal prothrombin contains approximately 10 mol of gamma-carboxyglutamic acid per mol of prothrombin. The coumadin-induced prothrombin which was bound to phospholipid contains approximately 6.5 mol of gamma-carboxyglutamic acid per mol of prothrombin while that which failed to bind to phospholipid has only 2.8 mol of gamma-carboxyglutamic acid per mol of zymogen. Thus, partially carboxylated prothrombins exist in the plasmas of coumarin-treated patients. Furthermore, there is a striking electrophoretic heterogeneity in the prothrombin preparations from the plasmas of the coumadin-treated patients. This most likely results from a wide spectrum of abnormal prothrombins with varying quantities of gamma-carboxyglutamic acid per mol of zymogen.
已从正常人类供体血浆以及服用香豆素的患者血浆中纯化出凝血酶原。将等摩尔量的正常凝血酶原或香豆素诱导的凝血酶原在Ca2+存在的情况下与磷脂微团一起孵育。随后对孵育混合物进行凝胶过滤，结果表明所有正常凝血酶原均与磷脂结合；而香豆素诱导的凝血酶原只有一半与磷脂结合。每摩尔凝血酶原中，正常凝血酶原约含10摩尔γ-羧基谷氨酸。与磷脂结合的香豆素诱导的凝血酶原，每摩尔凝血酶原约含6.5摩尔γ-羧基谷氨酸，而未与磷脂结合的香豆素诱导的凝血酶原，每摩尔酶原仅含2.8摩尔γ-羧基谷氨酸。因此，香豆素治疗患者的血浆中存在部分羧化的凝血酶原。此外，香豆素治疗患者血浆中的凝血酶原制剂存在明显的电泳异质性。这很可能是由于每摩尔酶原中γ-羧基谷氨酸含量不同的多种异常凝血酶原所致。
