Snell K, Natsumeda Y, Eble J N, Glover J L, Weber G
Laboratory for Experimental Oncology, Indiana University School of Medicine, Indianapolis 46223.
Br J Cancer. 1988 Jan;57(1):87-90. doi: 10.1038/bjc.1988.15.
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.
对来自患者的人结肠癌以及可移植大鼠肉瘤中丝氨酸生物合成酶3-磷酸甘油酸脱氢酶，以及丝氨酸利用的竞争酶丝氨酸羟甲基转移酶、丝氨酸脱水酶和丝氨酸转氨酶的活性进行了测定。丝氨酸脱水酶和丝氨酸转氨酶活性缺失，而在这两种肿瘤类型中3-磷酸甘油酸脱氢酶和丝氨酸羟甲基转移酶活性均显著增加。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，而甘氨酸和亚甲基四氢叶酸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用于核苷酸生物合成的利用相耦合，这是癌细胞对细胞复制生化承诺的一部分。这种模式在肉瘤和癌中均有发现，并且在人类和啮齿动物来源的肿瘤中也存在，这表明它对癌细胞生物化学具有普遍重要性，并将其作为抗癌化疗的潜在靶点凸显出来。
