第8章 核酸及降解和核苷酸代谢20101.pptVIP

* FIGURE 22-43 Biosynthesis of thymidylate (dTMP). The pathways are shown beginning with the reaction catalyzed by ribonucleotide reductase. Figure 22-44 gives details of the thymidylate synthase reaction. * FIGURE 22-44 Conversion of dUMP to dTMP by thymidylate synthase and dihydrofolate reductase. Serine hydroxymethyltransferase is required for regeneration of the N5,N10-methylene form of tetrahydrofolate. In the synthesis of dTMP, all three hydrogens of the added methyl group are derived from N5,N10-methylenetetrahydrofolate (pink and gray). * FIGURE 22-49a Thymidylate synthesis and folate metabolism as targets of chemotherapy. (a) During thymidylate synthesis, N5,N10-methylenetetrahydrofolate is converted to 7,8-dihydrofolate; the N5,N10-methylenetetrahydrofolate is regenerated in two steps (see Figure 22-44). This cycle is a major target of several chemotherapeutic agents. Lesch-Nyhan Syndrome Absence of HGPRTase X-linked (Gene on X) Occurs primarily in males Characterized by: Increased uric acid Spasticity Neurological defects Aggressive behavior Self-mutilation ● 别嘌呤醇无效 3 嘌呤核苷酸生物合成的调节 三个控制点： 5-P-核糖胺合成（转酰胺酶，IMP合成的第一步) ： 受产物IMP、GMP和AMP反馈调节。 IMP ? 腺苷酸琥珀酸（腺苷酸琥珀酸合成酶） 是IMP合成AMP的第一步：AMP（-） IMP ? XMP （IMP脱氢酶） IMP合成GMP的第一步 : GMP （-） ② ① ③ 腺苷酸琥珀酸合成酶 Gln 转酰胺酶 (二) 1 尿嘧啶核苷酸的合成： 前体：CO2 Gln 提供NH3 氨甲酰磷酸 Asp 首先由氨甲酰磷酸合成酶II 催化Gln将酰胺基氨和 HCO3-合成氨甲酰磷酸。 Gln + 2ATP + HCO3- 氨甲酰磷酸合成酶II 氨甲酰磷酸 2ADP + Pi + Glu (二) 嘧啶核糖核苷酸的合成 UMP CMP TMP 2ADP 课后阅读 尿嘧啶核苷酸的合成反应历程： 需4个高能磷酸键, 生成1个NADH 2 胞嘧啶核苷酸的合成 必须在UTP的水平上进行。 UTP→ CTP UMP 尿嘧啶核苷酸激酶 UDP 核苷二磷酸激酶 UTP ATP Mg2+ ADP ATP Mg2+ ADP 哺乳动物： UTP + Gln + ATP + H2O CTP合成酶 CTP + Glu +ADP +Pi E. coli中由UTP合成C