Zaharevitz D W, Napier E A, Anderson L W, Strong J M, Cysyk R L
Laboratory of Biological Chemistry, National Cancer Institute, Bethesda, MD 20892.
Eur J Biochem. 1988 Jul 15;175(1):193-8. doi: 10.1111/j.1432-1033.1988.tb14183.x.
De novo pyrimidine synthesis was studied in mouse liver, intestine, and kidney by intraperitoneal infusion of 15NH4Cl and analysis of 15N incorporation into uracil nucleotide pools. When the dose of a 1-h infusion of 15NH4Cl was increased from 50 mumol to 250 mumol the fraction of the total uracil nucleotide pool formed by de novo synthesis increased 4.0-fold in liver to 8.4% and 2.3-fold in intestine to 13.7%. The increase in intestine was independent of the increase in liver as evidenced by the lack of correlation between the increase observed in the intestine and liver of the same animal and the different distributions of label in the uracil ring nitrogens. A 2.4-fold increase in newly formed uracil nucleotides was observed in kidney when the infusion dose was raised from 150 mumol to 250 mumol. The increase in kidney was correlated with the increase in liver in the same animal and the distribution of label in the uracil ring nitrogens was similar to the distribution in liver. These results suggest that the increase in newly formed uracil nucleotides in intestine is due to increased de novo synthesis of pyrimidines in the intestine, while the increase in the kidney is due to increased salvage synthesis of uracil nucleotides from uridine synthesized in the liver and output to the circulation.
通过腹腔注射15NH4Cl并分析15N掺入尿嘧啶核苷酸池的情况，对小鼠肝脏、肠道和肾脏中的嘧啶从头合成进行了研究。当15NH4Cl 1小时注射剂量从50 μmol增加到250 μmol时，肝脏中从头合成形成的尿嘧啶核苷酸池在总尿嘧啶核苷酸池中所占比例增加了4.0倍，达到8.4%，肠道中增加了2.3倍，达到13.7%。肠道中的增加与肝脏中的增加无关，同一动物肠道和肝脏中观察到的增加之间缺乏相关性以及尿嘧啶环氮中标记物的不同分布证明了这一点。当注射剂量从150 μmol提高到250 μmol时，肾脏中新形成的尿嘧啶核苷酸增加了2.4倍。肾脏中的增加与同一动物肝脏中的增加相关，并且尿嘧啶环氮中标记物的分布与肝脏中的分布相似。这些结果表明，肠道中新形成的尿嘧啶核苷酸增加是由于肠道中嘧啶从头合成增加，而肾脏中的增加是由于从肝脏合成并输出到循环中的尿苷挽救合成尿嘧啶核苷酸增加。
