Human mitochondrial MTHFD2 is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase.
Human mitochondrial MTHFD2 is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase.
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DOI：
10.1186/s40170-017-0173-0
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发表时间：
2017
影响因子：
5.9
通讯作者：
Appling DR
中科院分区：
文献类型：
--
作者：
Shin M;Momb J;Appling DR
叶酸依赖的一碳代谢为几个生物过程提供一碳单位。该途径在真核生物中是高度区室化的，线粒体途径产生甲酸用于细胞质过程。据报道，线粒体酶MTHFD2使用NAD+作为辅因子，而同工酶MTHFD2L在生理相关条件下利用NAD+或NADP+。由于MTHFD 2在许多癌症类型中高度表达，我们试图确定这种酶的辅因子偏好。动力学分析表明，纯化的人MTHFD 2表现出双重氧化还原辅因子特异性，利用NADP+或NAD+与生理上更相关的五谷氨酸叶酸底物。这些结果表明，线粒体叶酸途径同工酶MTHFD 2和MTHFD 2L都表现出双重氧化还原辅因子特异性。我们的动力学分析清楚地支持MTHFD 2在线粒体NADPH产生中的作用，表明这种酶可能负责快速增殖细胞中线粒体产生NADH和NADPH。
Folate-dependent one-carbon metabolism provides one-carbon units for several biological processes. This pathway is highly compartmentalized in eukaryotes, with the mitochondrial pathway producing formate for use in cytoplasmic processes. The mitochondrial enzyme MTHFD2 has been reported to use NAD+ as a cofactor while the isozyme MTHFD2L utilizes NAD+ or NADP+ at physiologically relevant conditions. Because MTHFD2 is highly expressed in many cancer types, we sought to determine the cofactor preference of this enzyme. Kinetic analysis shows that purified human MTHFD2 exhibits dual redox cofactor specificity, utilizing either NADP+ or NAD+ with the more physiologically relevant pentaglutamate folate substrate. These results show that the mitochondrial folate pathway isozymes MTHFD2 and MTHFD2L both exhibit dual redox cofactor specificity. Our kinetic analysis clearly supports a role for MTHFD2 in mitochondrial NADPH production, indicating that this enzyme is likely responsible for mitochondrial production of both NADH and NADPH in rapidly proliferating cells.
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影响因子：
29
作者：
Ducker GS;Chen L;Morscher RJ;Ghergurovich JM;Esposito M;Teng X;Kang Y;Rabinowitz JD
通讯作者：
Rabinowitz JD
DOI：
10.1084/jem.20151574
发表时间：
2016-06-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Pikman Y;Puissant A;Alexe G;Furman A;Chen LM;Frumm SM;Ross L;Fenouille N;Bassil CF;Lewis CA;Ramos A;Gould J;Stone RM;DeAngelo DJ;Galinsky I;Clish CB;Kung AL;Hemann MT;Vander Heiden MG;Banerji V;Stegmaier K
通讯作者：
Stegmaier K
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
--
作者：
Nijhout, H. Frederik;Reed, Michael C.;Ulrich, Cornelia M.
通讯作者：
Ulrich, Cornelia M.
影响因子：
11.2
作者：
Gustafsson, Robert;Jemth, Ann-Sofie;Stenmark, Pal
通讯作者：
Stenmark, Pal