Enzymic imbalance in serine metabolism in human colon carcinoma and rat sarcoma.
Enzymic imbalance in serine metabolism in human colon carcinoma and rat sarcoma.
复制标题
人结肠癌和大鼠肉瘤中丝氨酸代谢中的酶不平衡。
DOI：
10.1038/bjc.1988.15
复制
发表时间：
1988-01
影响因子：
8.8
通讯作者：
Weber, G
中科院分区：
文献类型：
--
作者：
Snell, K;Natsumeda, Y;Eble, J N;Glover, J L;Weber, G
测定了人结肠癌患者和可移植大鼠肉瘤中丝氨酸生物合成酶3-磷酸甘油脱氢酶、丝氨酸羟甲基转移酶、丝氨酸脱水酶和丝氨酸氨基转移酶的活性。丝氨酸脱水酶和丝氨酸氨基转移酶活性缺失，而3-磷酸甘油脱氢酶和丝氨酸羟甲基转移酶活性显著升高。丝氨酸羟甲基转移酶催化甘氨酸和亚甲基四氢叶酸的形成，这两种物质是核苷酸生物合成的重要前体。在这些肿瘤中观察到的酶失衡确保了丝氨酸合成能力的增加与其对核苷酸生物合成的利用相结合，这是对癌细胞中细胞复制的生化承诺的一部分。在肉瘤和癌症以及人类和啮齿动物起源的肿瘤中发现了这种模式，这表明它对癌细胞的生物化学具有普遍的重要性，并将其单独作为抗癌化疗的潜在靶点。
The activities of 3-phosphoglycerate dehydrogenase, an enzyme of serine biosynthesis, and serine hydroxymethyltransferase, serine dehydratase and serine aminotransferase, which are competing enzymes of serine utilization, were assayed in human colon carcinomas from patients and in transplantable rat sarcomas. Serine dehydratase and serine aminotransferase activities were absent, whereas 3-phosphoglycerate dehydrogenase and serine hydroxymethyltransferase activities were markedly increased in both tumour types. Serine hydroxymethyltransferase catalyses the formation of glycine and methylene tetrahydrofolate which are important precursors for nucleotide biosynthesis. The observed enzymic imbalance in these tumours ensures that an increased capacity for the synthesis of serine is coupled to its utilisation for nucleotide biosynthesis as a part of the biochemical commitment to cellular replication in cancer cells. That this pattern is found in sarcomas and carcinomas, and in tumours of human and rodent origin, signifies its universal importance for the biochemistry of the cancer cell and singles it out as a potential target site for anti-cancer chemotherapy.