Mutoh Y
Nihon Seikeigeka Gakkai Zasshi. 1980 Dec;54(12):1733-43.
Vitamin K was thought to be primarily involved in the production of clotting factors. The recent findings of gamma-carboxyglutamic acid (Gla) - vitamin K-dependent calcium binding amino acid - in various calcified tissues, however, have prompted suggestions that vitamin K may play an important role in calcification mechanism. The present study was designed to investigate the relation between vitamin K and calcification. Morphological, biomechanical and biochemical analyses were undertaken on bones from vitamin K deficient rats raised on vitamin K deficient diet combined with administration of warfarin for three weeks. The Gla-containing proteins were extracted with EDTA from rat or bovine bones, partially isolated with gel filtration, and amino acid analysis was done. Gross roentgenographical and histological abnormalities were not observed in bones from vitamin K deficient rats in which prothrombin level was reduced to about 20 percent. There were no significant differences in values of Young's modulus, which were measured by three-point bending test, between vitamin K deficient and normal bones. No considerable alteration were noted in the protein, calcium or magnesium content of vitamin K deficient bone. Gla content of vitamin K deficient rat bone (per 1,000 residues of glutamic acid) was reduced by approximately 9% compared with that of normal rat bone. This observation supports the hypothesis that Gla biosynthesis in bone may be dependent on vitamin K. Calcium binding property of bovine bone Gla-containing protein was confirmed by the equilibrium dialysis procedure. Moderate amount of hydroxyproline was present in the Gla-containing proteins extracted from rats or bovine bones. It seems possible that biosynthesis of collagen and Gla protein of bone are somehow related, possibly at the level of procollagen. Further investigation is necessary to isolate Gla protein and clarify the correlation between collagen molecule and Gla protein biosynthesis.
维生素K曾被认为主要参与凝血因子的产生。然而，最近在各种钙化组织中发现了γ-羧基谷氨酸（Gla）——一种维生素K依赖的钙结合氨基酸，这提示维生素K可能在钙化机制中发挥重要作用。本研究旨在探讨维生素K与钙化之间的关系。对通过维生素K缺乏饮食并联合给予华法林饲养三周的维生素K缺乏大鼠的骨骼进行了形态学、生物力学和生化分析。用EDTA从大鼠或牛骨中提取含Gla的蛋白质，通过凝胶过滤进行部分分离，并进行氨基酸分析。在凝血酶原水平降至约20%的维生素K缺乏大鼠的骨骼中，未观察到明显的X线和组织学异常。通过三点弯曲试验测量的维生素K缺乏骨骼和正常骨骼之间的杨氏模量值没有显著差异。维生素K缺乏骨骼的蛋白质、钙或镁含量没有明显变化。与正常大鼠骨骼相比，维生素K缺乏大鼠骨骼的Gla含量（每1000个谷氨酸残基）降低了约9%。这一观察结果支持了骨骼中Gla生物合成可能依赖于维生素K的假说。通过平衡透析法证实了牛骨含Gla蛋白质的钙结合特性。从大鼠或牛骨中提取的含Gla蛋白质中存在适量的羟脯氨酸。骨胶原蛋白和Gla蛋白的生物合成似乎在某种程度上相关，可能在原胶原水平。需要进一步研究来分离Gla蛋白并阐明胶原分子与Gla蛋白生物合成之间的相关性。
