The folate cycle and disease in humans
The folate cycle and disease in humans
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DOI：
10.1046/j.1523-1755.2001.07851.x
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发表时间：
2001-02-01
影响因子：
19.6
通讯作者：
Fowler, B
中科院分区：
文献类型：
--
作者：
Fowler, B
高同型半胱氨酸血症在肾脏疾病患者中的患病率、其通过叶酸给药的治疗以及其通过亚甲基-四氢叶酸（亚甲基-THF）还原酶的677 C->T突变的加重已经确立叶酸循环作为肾脏疾病的发病机制和管理中的重要因素。叶酸循环的正常功能取决于相关酶的正常功能，足够的维生素及其在体内的正确配置。叶酸处置中的重要过程包括膳食叶酸聚谷氨酸盐转化为单谷氨酸盐、肠吸收、受体和载体介导的跨细胞膜转运以及细胞输出。叶酸辅酶负责中间代谢中的一碳单元转移，并且是关键代谢过程（例如嘌呤、嘧啶和甲硫氨酸合成以及甘氨酸和丝氨酸代谢）中的若干反应所需的。蛋氨酸合成酶及其还原蛋白和亚甲基四氢叶酸还原酶是同型半胱氨酸代谢中的关键叶酸酶。这些酶的缺陷是导致高胱氨酸尿症的罕见再甲基化缺陷中严重疾病的重要原因。了解它们的催化和分子特性对于理解中度高同型半胱氨酸血症的可能原因是重要的，例如，众所周知的亚甲基四氢叶酸还原酶的677 C->T转变。
The prevalence of hyperhomocysteinemia in renal disease patients, its treatment by folate administration, and its aggravation by the 677 C-->T mutation of methylene-tetrahydrofolate (methylene-THF) reductase has established the folate cycle as an important factor in the pathogenesis and management of renal disease. Proper function of the folate cycle depends on normal function of involved enzymes adequate of the vitamin and its correct disposition within the body. Vital processes in folate disposition include conversion of dietary folylpolyglutamates to monoglutamates, intestinal absorption, receptor and carrier-mediated transport across cell membranes, and cellular export. Folate coenzymes are responsible for the one-carbon unit transfer in intermediary metabolism and are required for several reactions in key metabolic processes, for example of purine, pyrimidine and methionine synthesis, and glycine and serine metabolism. Methionine synthase and its recently discovered reducing protein as well as methylene tetrahydrofolate reductase are key folate enzymes in homocysteine metabolism. Deficiencies of these enzymes are important causes of severe disease in the rare remethylation defects causing homocystinuria. Knowledge of their catalytic and molecular properties is important in understanding possible causes of moderate hyperhomocysteinemia, as for example, the well-known 677 C-->T transition of methylene tetrahydrofolate reductase.