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首页> 外文期刊>Life sciences >Phenotypes and circadian rhythm in utilization of formate in purine nucleotide biosynthesis de novo in adult humans.
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Phenotypes and circadian rhythm in utilization of formate in purine nucleotide biosynthesis de novo in adult humans.

机译：成年男子嘌呤核苷酸生物合成中利用甲酸的表型和昼夜节律。

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AIMS: Folate coenzymes and dependent enzymes introduce one carbon units at positions 2 (C(2)) and 8 (C(8)) of the purine ring during de novo biosynthesis. Formate is one source of one-carbon units. Although much is known about lower organisms, little data exists describing formate utilization for purine biosynthesis in humans. MAIN METHODS: Mass-spectrometric analysis of urinary uric acid, the final purine catabolite, following 1.0 g oral doses of sodium [(13)C] formate was performed and detected (13)C enrichment at C(2) and C(8) separately. KEY FINDINGS: Three phenotypes were suggested. One incorporates (13)C 0.72 to 2.0% into C(2) versus only 0 to 0.07% into C(8). Another incorporates only 0 to 0.05% (13)C into C(2) or C(8). A third phenotype incorporates (13)C into C(8) (0.15%) but C(2) incorporation (0.44%) is still greater. In subjects who incorporated (13)C formate into C(2), peak enrichment occurred in voids from 8-12 h (24 h clock) suggesting a circadian rhythm. SIGNIFICANCE: Evidence that mammalian liver introduces C(8) and that C(2) is introduced in a non-hepatic site would explain our results. Our data are not similar to those in non-mammalian organisms or cells in culture and are not consistent with the hypothesis that formate from folate-dependent metabolism in mitochondria is a major one carbon source for purine biosynthesis. Timing of peak (13)C enrichment at C(2) corresponds to maximal DNA synthesis in human bone marrow. Phenotypes may explain the efficacy (or lack of) of certain anticancer and immunosuppressive drugs.
机译：目的：叶酸辅酶和依赖性酶在从头生物合成过程中在嘌呤环的位置2（C（2））和8（C（8））处引入一个碳单位。甲酸盐是一碳单位的一种来源。尽管人们对低等生物认识很多，但很少有数据描述甲酸在人类中用于嘌呤生物合成的利用。主要方法：口服1.0 g甲酸钠[（13）C]甲酸钠后，对尿酸，最终嘌呤分解代谢产物进行尿素质谱分析，并在C（2）和C（8）处检测到（13）C富集。分别。主要发现：提出了三种表型。一个将（13）C的0.72到2.0％掺入了C（2）中，而仅将0到0.07％的C掺入了C（8）中。另一个仅将0到0.05％（13）C掺入C（2）或C（8）中。第三种表型将（13）C掺入C（8）（0.15％），但C（2）掺入（0.44％）更大。在将（13）C甲酸酯掺入C（2）中的受试者中，在8-12小时（24小时制）的空隙中出现了峰富集，表明昼夜节律。意义：哺乳动物肝脏中引入C（8）且在非肝部位引入C（2）的证据将解释我们的结果。我们的数据与非哺乳动物生物或培养细胞中的数据不同，并且与线粒体中叶酸依赖的代谢形成的甲酸盐是嘌呤生物合成的主要碳源的假设不一致。 C（2）处的峰（13）C富集的时间对应于人类骨髓中最大的DNA合成。表型可以解释某些抗癌和免疫抑制药物的功效（或缺乏）。

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