Bukin Iu V, Sergeev A V, Kondrat'eva G Ia
Biokhimiia. 1976 Mar;41(3):432-42.
A simple method of isolation of partially purified puridoxal kinase preparation from mouse liver, having specific activity of 600-700 E/mg protein and a 30% yield is described. It is demonstrated that of all number of 2-alkyl- and 4'-O-methyl pyridoxol analogs synthesized, 4'-O-methyl-pyridoxol (Ki=0.2-10(-5) M, Km(pyridoxal)=4-10(-5) M) is the most active competitive inhibitor of pyridoxal kinase. 3-Deoxy-4'-O-methylpyridoxol is a non-competitive inhibitor of pyridoxal kinase, the latter having an affinity for the enzyme 16 times lower than that of 4'-O-methylpyridoxol. 2-Alkyl analogs of pyridoxol exhibit properties of competitive inhibitors; the affinity of 2'-ethylpyridoxol for the enzyme is 5 times lower than that of 2'-methylpyridoxol; corresponding 2-alkyl derivatives of dimethyl ethers of 3-hydroxycinchomeronic acids have no pronounced affinity for the enzyme. The study of the toxic effects of pyridoxol analogs on the central nervous system has revealed inverse dependence between the neurotoxic dose of the compound and its efficiency as an inhibitor of pyridoxal kinase (Km/Ki value).
描述了一种从鼠肝中分离部分纯化的吡哆醛激酶制剂的简单方法，其比活性为600 - 700 E/mg蛋白质，产率为30%。结果表明，在合成的所有2-烷基和4'-O-甲基吡哆醇类似物中，4'-O-甲基吡哆醇（Ki = 0.2 - 10(-5) M，Km（吡哆醛）= 4 - 10(-5) M）是吡哆醛激酶最具活性的竞争性抑制剂。3-脱氧-4'-O-甲基吡哆醇是吡哆醛激酶的非竞争性抑制剂，其对该酶的亲和力比4'-O-甲基吡哆醇低16倍。吡哆醇的2-烷基类似物表现出竞争性抑制剂的特性；2'-乙基吡哆醇对该酶的亲和力比2'-甲基吡哆醇低5倍；3-羟基辛可芬酸二甲醚的相应2-烷基衍生物对该酶没有明显的亲和力。对吡哆醇类似物对中枢神经系统的毒性作用研究表明，化合物的神经毒性剂量与其作为吡哆醛激酶抑制剂效率（Km/Ki值）之间呈反比关系。
