Metabolism of Nucleotides Summarise l Digestion and absorption

第八章 核苷酸代谢 Metabolism of Nucleotides

Summarise l Digestion and absorption of nucleic acid Nucleoprotein Nucleic acid（RNA, DNA） Protein Nuclease Nucleotidase Phosphate Nucleosidase Base Ribose

第一节 嘌呤核苷酸的代谢 Metabolism of Purine Nucleotides

一、嘌呤核苷酸的合成代谢 Biosynthesis of purine nucleotides l 从头合成途径 (de novo synthesis pathway) l 补救合成途径 (salvage synthesis pathway)

• 嘌呤碱合成的元素来源 • Element sources of purine bases CO 2 天冬氨酸 Aspartate 甘氨酸 Glycine 甲酰基 （一碳单位） One carbon unit 谷氨酰胺 （酰胺基） Glutamine

v Ribose 5 -phosphate is synthesized by the pentose phosphate pathway. Ribose 5 -phosphate is phosphorylated by ATP to yield 5 -phosphoribosyl-1 pyrophosphate(PRPP). v Glutamine contributes an amino group that displaces pyrophosphate from the 1’ position of the ribose ring.

AMP 激酶 ATP GMP ADP 激酶 ATP GDP ADP 激酶 ATP ADP GTP

• 从头合成的调节 • Regulation of De novo synthesis of Purine Nucleotides 调节方式：反馈调节和交叉调节 _ _ _ + + 腺苷酸代 R-5 -P PRPP合成酶 酰胺转移酶 PRPP PRA _ ATP IMP 琥珀酸 XMP _ AMP ADP ATP GMP GDP GTP _ IMP 腺苷酸代 琥珀酸 + GTP XMP ATP AMP ADP ATP +GMP GDP GTP _ 目录

• 参与补救合成的酶 腺嘌呤磷酸核糖转移酶 (adenine phosphoribosyl transferase, APRT) 次黄嘌呤-鸟嘌呤磷酸核糖转移酶(hypoxanthineguanine phosphoribosyl transferase, HGPRT) 腺苷激酶(adenosine kinase)

• 合成过程 腺嘌呤 + PRPP 次黄嘌呤 + PRPP APRT AMP + PPi HGPRT 鸟嘌呤 + PRPP HGPRT 腺嘌呤核苷 IMP + PPi GMP + PPi 腺苷激酶 ATP ADP AMP

v The degradation of purines leads to the production of uric acid. Adenine is degraded into hypoxanthine, whereas guanine is degraded into xanthine. Hypoxanthine is transformed into xanthine by xanthine oxidase, and xanthine is then converted to uric acid. v Humans degrade purines into uric acid, which is excreted in the urine.

第二节 嘧啶核苷酸的代谢 Metabolism of Pyrimidine Nucleotides

一、嘧啶核苷酸的合成代谢 Biosynthesis of pyrimidine nucleotides l 从头合成途径de novo synthesis pathway l 补救合成途径salvage synthesis pathway

• 嘧啶合成的元素来源 • Element source of pyrimidine base 氨基甲 酰磷酸 Carbamoyl phosphate 天冬氨酸 Aspartate

• 合成过程 1. 尿嘧啶核苷酸的合成 2. Synthetic pathway of UMP 谷氨酰胺 + HCO 3氨基甲酰磷酸合成酶II Carbamoyl phosphate synthase Ⅱ 2 ATP 2 ADP+Pi 谷氨酸 + 氨基甲酰磷酸 Carbamoyl phosphate

2. 胞嘧啶核苷酸的合成 Synthesis of CTP Uridine monophosphate kinase 尿苷酸激酶 ATP ADP CTP synthetase UTP CTP合成酶 谷氨酰胺 ATP 谷氨酸 ADP+Pi UDP Uridine diphosphate kinase 二磷酸核苷激酶 ATP ADP

3. d. TMP或TMP的生成 UDP CTP 脱氧核苷酸还原酶 CDP d. UDP d. CMP TMP synthetase TMP合酶 N 5, N 10 -甲烯FH 4 FH 2还原酶 NADP+ d. UMP FH 2 NADPH+H+ 脱氧胸苷一磷酸 d. TMP