Thorndike J, Beck W S
Cancer Res. 1977 Apr;37(4):1125-32.
Extracts of human normal and leukemic leukocytes contain an enzyme that catalyzes a transfer of labeled methyl carbon from N5-[14C]methyltetrahydrofolate to tryptamine. Evidence is presented that this reaction is not attributable to a methyltransferase but to the following reaction sequence: (a) an oxidation of N5-[14C]methyltetrahydrofolate to N5, N10-[14C]methylenetetrahydrofolate that is catalyzed by N5, N10-methylenetetrahydrofolate reductase (EC 1.1.1.68); (b) spontaneous release of [14C]formaldehyde from N5, N10-[14C]methylenetetrahydrofolate; and (c) nonenzymatic condensation of [14C]formaldehyde with tryptamine to form a radioactive carboline derivative. The occurrence of this sequence in leukocytes is suggested by data that show that the enzyme reaction is strongly stimulated by addition of flavin adenine dinucleotide and that the final product is chromatographically identical to the adduct formed in the reaction of [14C]formaldehyde with tryptamine. In the absence of tryptamine, a product accumulates that can react with other HCHO acceptors, i.e., beta-phenylethylamine and dimedone; another reaction product is tetrahydrofolate. Production of formaldehyde is relatively more active in normal lymphocytes than in normal granulocytes, but it is even higher in lymphocytes of chronic lymphocytic leukemia. Activity in granulocytes from a subject with chronic myelocytic leukemia is also elevated but to a lesser extent than activity in lymphocytes of chronic lymphocytic leukemia. Activity in granulocytes from a subject with chronic myelocytic leukemia is also elevated but to a lesser extent than activity in lymphocytes of chronic lymphocytic leukemia. Formaldehyde production in leukocytes is only slightly stimulated by addition of various cobalamins, and activity is normal in leukocytes from a vitamin B12-deficient patient. We conclude that the system is cobalamin independent. Thus, there exists an active pathway from N5-methyltetrahydrofolate to tetrahydrofolate other than the one catalyzed by cobalamin-dependent N5-methyltetrahydrofolate-homocysteine methyltransferase.
人正常白细胞和白血病白细胞提取物中含有一种酶，该酶可催化将标记的甲基碳从N5-[14C]甲基四氢叶酸转移至色胺。有证据表明，此反应并非归因于甲基转移酶，而是归因于以下反应序列：(a) N5-[14C]甲基四氢叶酸被N5,N10-亚甲基四氢叶酸还原酶（EC 1.1.1.68）催化氧化为N5,N10-[14C]亚甲基四氢叶酸；(b) [14C]甲醛从N5,N10-[14C]亚甲基四氢叶酸中自发释放；以及(c) [14C]甲醛与色胺非酶促缩合形成放射性咔啉衍生物。白细胞中该序列的存在由以下数据表明：酶反应因添加黄素腺嘌呤二核苷酸而受到强烈刺激，且最终产物在色谱上与[14C]甲醛与色胺反应形成的加合物相同。在无色胺的情况下，会积累一种可与其他甲醛受体（即β-苯乙胺和二甲基酮）反应的产物；另一种反应产物是四氢叶酸。正常淋巴细胞中甲醛的产生相对比正常粒细胞更活跃，但在慢性淋巴细胞白血病的淋巴细胞中甚至更高。慢性粒细胞白血病患者粒细胞中的活性也有所升高，但程度低于慢性淋巴细胞白血病淋巴细胞中的活性。慢性粒细胞白血病患者粒细胞中的活性也有所升高，但程度低于慢性淋巴细胞白血病淋巴细胞中的活性。添加各种钴胺素仅轻微刺激白细胞中甲醛的产生，且维生素B12缺乏患者白细胞中的活性正常。我们得出结论，该系统不依赖钴胺素。因此，除了由钴胺素依赖性N5-甲基四氢叶酸-同型半胱氨酸甲基转移酶催化的途径外，还存在一条从N5-甲基四氢叶酸到四氢叶酸的活跃途径。
