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Modulation of pentose phosphate pathway during cell cycle progression in human colon adenocarcinoma cell line HT29.
磷酸戊糖途径在人结肠腺癌细胞系 ht29 细胞周期进程中的调节。

摘要

Cell cycle regulation is dependent on multiple cellular and molecular events. Cell proliferation requires metabolic sources for the duplication of DNA and cell size. However, nucleotide reservoirs are not sufficient to support cell duplication and, therefore, biosynthetic pathways should be upregulated during cell cycle. Here, we reveal that glucose-6-phosphate dehydrogenase (G6PDH) and transketolase (TKT), the 2 key enzymes of oxidative and nonoxidative branches of the pentose phosphate pathway (PPP), respectively, which is necessary for nucleotide synthesis, are enhanced during cell cycle progression of the human colon cancer cell line HT29. These enhanced enzyme activities coincide with an increased ratio of pentose monophosphate to hexose monophosphate pool during late G1 and S phase, suggesting a potential role for pentose phosphates in proliferating signaling. Isotopomeric analysis distribution of nucleotide ribose synthesized from 1,2-(13)C(2)-glucose confirms the activation of the PPP during late G1 and S phase and reveals specific upregulation of the oxidative branch. Our data sustain the idea of a critical oxidative and nonoxidative balance in cancer cells, which is consistent with a late G1 metabolic check point. The distinctive modulation of these enzymes during cell cycle progression may represent a new strategy to inhibit proliferation in anticancer treatments.

译文

细胞周期调控依赖于多种细胞和分子事件。细胞增殖需要代谢源来复制 DNA 和细胞大小。然而,核苷酸库不足以支持细胞复制,因此,生物合成途径应该在细胞周期中上调。在此,我们揭示了葡萄糖-6-磷酸脱氢酶 (G6PDH) 和转酮醇酶 (TKT),分别是磷酸戊糖途径 (PPP) 的氧化和非氧化分支的 2 个关键酶, 这是核苷酸合成所必需的,在人结肠癌细胞系 ht29 的细胞周期进程中增强。这些增强的酶活性与 G1 后期和 S 期戊糖单磷酸盐与己糖单磷酸盐池的比率增加相一致,表明戊糖磷酸盐在增殖信号中的潜在作用。从 1,2-(13) C (2)-葡萄糖合成的核苷酸核糖的同位素分析分布证实了 PPP 在 G1 后期和 S 期的激活,并揭示了氧化分支的特异性上调。我们的数据支持了癌细胞中关键氧化和非氧化平衡的观点,这与 G1 代谢晚期检查点一致。这些酶在细胞周期进程中的独特调节可能代表了在抗癌治疗中抑制增殖的新策略。

Pentose phosphate pathway

肾内泌尿 生化过程 临床研究术语
概述  :  

戊糖磷酸途径是一种平行于糖酵解的代谢途径,它产生NADPH和戊糖(5-碳糖),以及核糖5-磷酸(核苷酸合成的前体)。虽然戊糖磷酸途径确实涉及葡萄糖的氧化,但其主要作用是合成代谢而非分解代谢。该途径在红细胞中尤其重要。该途径有两个不同的阶段:第一个是氧化相,在其中生成NADPH,第二个是5碳糖的非氧化合成。 作用机理 ①氧化相:在此阶段,两个分子NADP +被还原成NADPH,从转化利用能量葡萄糖-6-磷酸成核酮糖5-磷酸。整个反应

pentose   英 /'pentəʊz; -s/   美 /'pɛntos/

释    义   n. [有化] 戊糖

例    句   Another aldonic acid, gluconic acid, is an intermediate in the pentose phosphate pathway.另一个重要的醛酸,葡萄糖酸是戊糖磷酸途径的中间产物。

 

phosphate   英 /ˈfɒsfeɪt/   美 /ˈfɑːsfeɪt/

释    义   n. 磷酸盐;皮膜化成

例    句   Humans need a healthy diet and keeping the balance of phosphate in the diet may be important for a healthy life and longevity.研究人员表示:“人们需要健康的饮食,保持饮食中磷酸盐摄入的平衡可能对健康和长寿非常重要。

 

pathway   英 /ˈpɑːθweɪ/   美 /ˈpæθweɪ/

释    义   n. 路,道;途径,路径;神经通路

例    句   What's changing along here is the what's changing along this pathway is the expression pattern of genes in cells.因此这里改变的是,在这条途径上改变的是基因表达的模式

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