Trakatellis A, Dimitriadou A, Trakatelli M
Department of Biological Chemistry, Medical School, Aristoteles University of Thessaloniki, Greece.
Postgrad Med J. 1997 Oct;73(864):617-22. doi: 10.1136/pgmj.73.864.617.
Pyridoxine deficiency leads to impairment of immune responses. It appears that the basic derangement is the decreased rate of production of one-carbon units necessary for the synthesis of nucleic acids. The key factor is a pyridoxine enzyme, serine hydroxymethyltransferase. This enzyme is very low in resting lymphocytes but increases significantly under the influence of antigenic or mitogenic stimuli, thus supplying the increased demand for nucleic acid synthesis during an immune response. Serine hydroxymethyltransferase activity is depressed by deoxypyridoxine, a potent antagonist of pyridoxal phosphate, and also by known immunosuppressive or antiproliferative agents. The combination of these agents is additive. Our results lead us to suggest the following medical applications: (a) combination of deoxypyridoxine with immunosuppressive or chemotherapeutic drugs may be effective in cases of immunosuppressive therapy or organ transplantation, (b) the development of special agents directed against the serine hydroxymethyltransferase apoprotein may prove to be a valuable medical tool, since this enzyme presents an excellent target for chemotherapy, (c) lymphocytes of individual patients could be used to design tailor-made specific immunosuppressive or chemotherapeutic treatment, and (d) the serine hydroxymethyltransferase activity of lymphocyte culture presents an excellent indicator for the evaluation of potency of immunosuppressive, chemotherapeutic or genotoxic compounds in a simple and rapid test.
维生素B6缺乏会导致免疫反应受损。基本的紊乱似乎是核酸合成所需的一碳单位生成速率降低。关键因素是一种维生素B6酶，即丝氨酸羟甲基转移酶。这种酶在静息淋巴细胞中含量很低，但在抗原或有丝分裂原刺激的影响下会显著增加，从而满足免疫反应期间对核酸合成增加的需求。丝氨酸羟甲基转移酶的活性会被脱氧吡哆醇（一种磷酸吡哆醛的强效拮抗剂）以及已知的免疫抑制或抗增殖剂所抑制。这些药物的联合作用是相加的。我们的研究结果促使我们提出以下医学应用建议：（a）在免疫抑制治疗或器官移植的情况下，脱氧吡哆醇与免疫抑制或化疗药物联合使用可能有效；（b）开发针对丝氨酸羟甲基转移酶载脂蛋白的特殊药物可能会成为一种有价值的医学工具，因为这种酶是化疗的一个理想靶点；（c）个体患者的淋巴细胞可用于设计量身定制的特异性免疫抑制或化疗治疗方案；（d）淋巴细胞培养中的丝氨酸羟甲基转移酶活性在一个简单快速的测试中是评估免疫抑制、化疗或遗传毒性化合物效力的一个理想指标。
