Bertrand R, Beauchemin M, Dayan A, Ouimet M, Jolivet J
Centre de Recherche Louis-Charles Simard, Institut du Cancer de Montréal, Canada.
Biochim Biophys Acta. 1995 May 12;1266(3):245-9. doi: 10.1016/0167-4889(95)00020-s.
We present evidence for the presence of the folate metabolism enzyme methenyltetrahydrofolate synthetase (MTHFS) in mitochondria. MTHFS activity was identified in the matrix of mitochondria purified from human liver biopsies. Mitochondrial and cytoplasmic MTHFS specific activities are similar, 85% of the total cellular MTHFS activity is in the cytoplasm and both native enzymes have similar molecular weights (approximately 25 kDa). Studies using purified mitochondrial MTHFS from CA46 human Burkitt lymphoma cells reveal that mitochondrial MTHFS behaves kinetically like the cytoplasmic enzyme with Km values of 4.7, 0.8 and 22 microM respectively for (6R,S)-5-formyltetrahydrofolate monoglutamate, (6S)-5-formyltetrahydrofolate pentaglutamate and ATP. This finding adds to previous observations that various folate-dependent enzymes reside in the mitochondria of eucaryotic cells. Intracellular tetrahydrofolate metabolism is highly compartmentalized and mitochondrial MTHFS activity is necessary for the entry of mitochondrial 5-formyltetrahydrofolate into the mitochondrial folate pool.
我们提供了线粒体中存在叶酸代谢酶亚甲基四氢叶酸合成酶（MTHFS）的证据。在从人肝脏活检组织中纯化的线粒体基质中鉴定出了MTHFS活性。线粒体和细胞质中的MTHFS比活性相似，细胞总MTHFS活性的85%存在于细胞质中，且两种天然酶的分子量相似（约25 kDa）。使用从CA46人伯基特淋巴瘤细胞中纯化的线粒体MTHFS进行的研究表明，线粒体MTHFS在动力学上与细胞质酶相似，对于（6R,S）-5-甲酰四氢叶酸单谷氨酸、（6S）-5-甲酰四氢叶酸五谷氨酸和ATP，其Km值分别为4.7、0.8和22 microM。这一发现进一步证实了先前的观察结果，即各种叶酸依赖性酶存在于真核细胞的线粒体中。细胞内四氢叶酸代谢高度分区化，线粒体MTHFS活性是线粒体5-甲酰四氢叶酸进入线粒体叶酸池所必需的。
