Regulation of the balance of one-carbon metabolism in Saccharomyces cerevisiae
Regulation of the balance of one-carbon metabolism in Saccharomyces cerevisiae
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DOI：
10.1074/jbc.m004248200
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发表时间：
2000-10-06
影响因子：
4.8
通讯作者：
Dawes, IW
中科院分区：
文献类型：
--
作者：
Piper, MD;Hong, SP;Dawes, IW
酵母中的一碳代谢是一个重要的过程，它依赖于三种一碳供体分子中的至少一种：丝氨酸、甘氨酸或甲酸盐。通过遗传学和生物化学的结合，我们已经展示了细胞如何通过调节细胞质丝氨酸羟甲基转移酶在过量存在的副反应中的活性来调节供体之间的一碳分子的平衡。 甘氨酸，该控制控制细胞质中 5,10-亚甲基四氢叶酸 (5,10-CH2-H(4) 叶酸) 的水平，其在关键基因表达的信号传导转录控制中具有直接作用，特别是那些编码甘氨酸脱羧酶复合物的独特成分（GCV1、GCV2 和 GCV3）的基因。基于这些和其他观察，我们 提出了一个模型，用于解释当带电叶酸有限或甘氨酸过量时，细胞如何平衡补充其单碳池的需要。我们还提出，在正常情况下，细胞质的5,10-CH2-H(4)叶酸主要通过蛋氨酸生成甲基，而线粒体中甘氨酸生成的一碳单位更多地用于嘌呤生物合成，当甘氨酸过量时，5,10-CH2-H(4)叶酸减少，调节环路改变了生成的平衡。 一碳单位进入线粒体。
One-carbon metabolism in yeast is an essential process that relies on at least one of three one-carbon donor molecules: serine, glycine, or formate, By a combination of genetics and biochemistry we have shown how cells regulate the balance of one-carbon mow between the donors by regulating cytoplasmic serine hydroxymethyltransferase activity in a side reaction occurring in the presence of excess glycine, This control governs the level of 5,10-methylene tetrahydrofolate (5,10-CH2-H(4)folate) in the cytoplasm, which has a direct role in signaling transcriptional control of the expression of key genes, particularly those encoding the unique components of the glycine decarboxylase complex (GCV1, GCV2, and GCV3), Based on these and other observations, we propose a model for how cells balance the need to supplement their one-carbon pools when charged folates are limiting or when glycine is in excess. We also propose that under normal conditions, cytoplasmic 5,10-CH2-H(4)folate is mainly directed to generating methyl groups via methionine, whereas one-carbon units generated from glycine in mitochondria are more directed to purine biosynthesis, When glycine is in excess, 5,10-CH2-H(4)folate is decreased, and the regulation loop shifts the balance of generation of one-carbon units into the mitochondrion.