二氢叶酸还原酶
生物化学
酶
蛋氨酸合酶
化学
丝氨酸
蛋氨酸
辅因子
嘌呤
氨基酸
甲氨蝶呤
分解代谢
核苷酸
生物
基因
免疫学
标识
DOI:10.1007/978-1-4615-2960-6_80
摘要
Tetrahydrofolate coenzymes play critical roles in a host of cellular one-carbon transfer reactions. Among these are the de novo biosynthesis of both purine and pyrimidine nucleotides (and thus both ATP and DNA), the methylation of homocysteine to methionine, the interconversion of serine and glycine, and the catabolism of certain amino acids. Dihydrofolate reductase (DHFR) plays a central role in the majority of these metabolic reactions, for it is required for the regeneration of tetrahydrofolate from dihydrofolate, and thus is responsible for maintaining a constant cellular supply of this critical coenzyme. 1 Inhibitors of DHFR thus have the potential to be potent antiproliferative agents, since they interfere with many cellular processes critical for cell growth. The deleterious consequences with respect to normal cells are certainly responsible in part for the extreme toxicity of DHFR inhibitors such as methotrexate, and severely limit their clinical usefulness in cancer chemotherapy.2–6
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