Trakatellis A, Dimitriadou A, Exindari M, Scountzou J, Koliakos G, Christodoulou D, Malissiovas N, Antoniadis A, Polyzoni T
Department of Biochemistry, Medical School, Aristotle University of Thessaloniki, Greece.
Postgrad Med J. 1992;68 Suppl 1:S70-7.
Measurements of serine hydroxymethyltransferase (SHMT) in resting lymphocyte cultures showed that the level of activity of this enzyme was very low. Under the influence of mitogenic stimuli serine hydroxymethyl-transferase activity was induced 5-20-fold. Addition in the cultures of 4-deoxypyridoxine, a potent antagonist of vitamin B6 coenzymes, concurrently with the mitogen, inhibits the induction of serine hydroxymethyltransferase. Thus deoxypyridoxine exerts its effects not only at the level of the enzyme itself by antagonizing the coenzyme but also at the level of its biosynthesis. Synchronous addition of vitamin B6 with deoxypyridoxine effectively reverses the inhibitory effects. The T helper cells of the lymphocyte culture are very sensitive to deoxypyridoxine action in contrast to T suppressor cells. The effect of phytohaemagglutinin or concanavalin A on the production of interleukin-1b, interleukin-2 and interleukin-2 receptors is profoundly affected by deoxypyridoxine. These results give a deeper insight of the mechanisms by which pyridoxine deficiency causes significant reduction of humoral and cellular immune responses to antigenic stimuli. On the basis of the data of this report a detailed illustration of the events that follow the T cell activation is presented. From this investigation the enzyme serine hydroxymethyltransferase emerges as a key element in the processes of immune responses and cell proliferation. Based on this finding we advance the following two propositions for possible future medical application: (i) combination of deoxypyridoxine with immunosuppressive drugs in case of immunosuppressive therapy or organ transplantation. (ii) the enzyme presents an excellent target for chemotherapy and therefore development of special agents directed against its apoprotein may prove to be a very valuable medical tool.
对静息淋巴细胞培养物中的丝氨酸羟甲基转移酶（SHMT）进行测量发现，该酶的活性水平非常低。在促有丝分裂刺激的影响下，丝氨酸羟甲基转移酶的活性被诱导提高了5至20倍。在培养物中与促有丝分裂原同时添加4-脱氧吡哆醇（一种维生素B6辅酶的强效拮抗剂），可抑制丝氨酸羟甲基转移酶的诱导。因此，脱氧吡哆醇不仅通过拮抗辅酶在酶本身水平发挥作用，还在其生物合成水平发挥作用。维生素B6与脱氧吡哆醇同步添加可有效逆转抑制作用。与T抑制细胞相比，淋巴细胞培养物中的T辅助细胞对脱氧吡哆醇的作用非常敏感。脱氧吡哆醇对植物血凝素或伴刀豆球蛋白A对白介素-1β、白介素-2和白介素-2受体产生的影响有深远作用。这些结果更深入地揭示了吡哆醇缺乏导致对抗抗原刺激的体液和细胞免疫反应显著降低的机制。基于本报告的数据，对T细胞激活后发生的事件进行了详细说明。从这项研究中可以看出，丝氨酸羟甲基转移酶是免疫反应和细胞增殖过程中的关键要素。基于这一发现，我们提出以下两个可能在未来医学应用中的命题：（i）在免疫抑制治疗或器官移植时，将脱氧吡哆醇与免疫抑制药物联合使用。（ii）该酶是化疗的极佳靶点，因此开发针对其脱辅基蛋白的特殊药物可能是一种非常有价值的医学工具。
