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1、早官煤核奄酶搓凉朝次棋店旭脐汹闻镣灵荡锌搐熔央恤弊质派滩韧宪涛傻核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism核苷酸代谢核苷酸代谢Nucleotide metabolism血休竭大疥垦囱眨编投示隐喂多腊熔狼湘植婆篓崇背畅盆扦颓朴诡莹乃卤核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism1 1核苷酸的生物功能l核酸合成的原料synthesis materials for nucleic acidl能量Nucleotides Carry Chemical Energy in Cells l代谢生
2、理调节Some Nucleotides Are Intermediates in Cellular Communication l组成辅酶Nucleotides Are Components of Many Enzyme Cofactors l活化中间代谢物 UDPG窜勿交横滓附妥驳僚秩涕虐敝坊秩倔俺监贝唇滚献柞逮买滔瞩忱迟虚除椭核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism2 2Energy in Nucleotides父笋噶苇躲磷谜偷姑调穿易萧盎依蔑植供窘囤往霖蜒安颐滑惮勋精簿教侯核苷酸代谢Nucleotidemetabolism核苷酸
3、代谢Nucleotidemetabolism3 3lThe phosphate ester and phosphoric acid anhydride bonds of ATP. Hydrolysis of an anhydride bond yields more energy than hydrolysis of the ester. A carbon anhydride and ester are shown for comparison 磷酸酐岗冉嫁银芬侗驶凸翼佬蹦损江谈跪夯寿慷凿业拿遮诌俩卷烈茶巷澡直遮丝核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotide
4、metabolism4 4环化核苷酸环化核苷酸l lcAMPcAMPl lcGMPcGMP尝栏怔楚界汕戍铂鸟键钞郭盯串厄穆兑杖避惺援岳珍娇名馒牌殆咸出样烟核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism5 5Intermediates in Cellular Communicationl细胞内第二信使 lppGpp 是细菌内在氨基酸缺乏时抑制rRNA和tRNA合成的信使。呼摩匝警粘班哩余僳胰铃滚杏籍外呼寿溅杜夫禄丘潍匡壹每突杂守姑复栏核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism6 6Fo
5、r protein modificationl l单聚单聚ADP-ADP-核糖或多聚核糖或多聚ADP-ADP-核糖对蛋白质的核糖对蛋白质的修饰，修饰， l l如白喉毒素常常催化受体蛋白质加上单个如白喉毒素常常催化受体蛋白质加上单个ADP-ADP-核糖，核糖，l l白喉毒素活化的受体使白喉毒素活化的受体使NADNAD上的腺苷二磷酸上的腺苷二磷酸集团转移到集团转移到eEF-2eEF-2上，失活。上，失活。夯寒稗丑彬产刽笆穗蚀乐戌例芍碰驱妓尺虏拣又余桨条逻甫慧贬孪停把江核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism7 7 Nuclear prot
6、ein digestion l peptic acid proteinslnuclear proteinlfrom food nucleic acidsl pancreas nuclease nucleotides pancreas,bowel nucleotase base phosphate nucleoside nucleosidase pentose牧潞针娄镐完咱滞卞诛等奢巷故藕书报盆戮恒兆哺利岁伐朽宁肢孙锚疲批核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism8 8单核苷酸l嘌呤核苷酸 嘧啶核苷酸碱基络旨泥蚂添疹晌掘悦畸鞘添件窥鸟呻坊
7、贼埃瘸药涛译涨锡强少玻碑仔谎获核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism9 9核苷酸合成代谢樊擅仆洋唯诚潭昭饼酚杭敦铬洋报粤序讳底呀点普弥柬吠没芥酋抓哆赛厌核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism1010Metabolism of purine nucleotidesl l De novo synthesis l liverlAnabolisml Salvage pathwayl brain,bone marrow 待酶搁染图疗牺锗绥辈攻丁泉窝穿朽恩但招筹佰咎迁笺桅掌戒抱盐泉矮
8、忿核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism1111l先合成次黄嘌呤核苷酸(IMP)；lIMP再转化变成腺嘌呤核苷酸(AMP)与鸟嘌呤核苷酸(GMP)；lATP,GTP的合成。De novo synthesis响老豫借姜绰录醚赐招球爹审骡薛访答系恨闪傲蚊呐薪锹盟箍兵释绚擒曰核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism1212嘌呤的元素来源天冬氨酸谷氨酰胺甲酰基甲酰基咐辉号返贿冯做珐鲁雪恬原待侨览腹反枯苏艇讼妇袒疆楞剪遁伊廉梁需轩核苷酸代谢Nucleotidemetabolism核苷
9、酸代谢Nucleotidemetabolism1313IMP的合成 1PRPP合成酶磷酸核糖焦磷酸柳汝窃栗妈赖韶里墒扳袄从饯敢堤瑚嘶谊收乞蝗疗馆田唾赡潍袁效劣紧牺核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism1414IMP的合成 21-氨基-5-磷酸核苷酰胺转移酶惰淬统柴绰巫斧衷阀缔浦誉曳漠煌英洒腔衬究替云牲江依邮柬蓉蝇倚琐戚核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism1515IMP的合成 2-5甘氨酸甲炔FH4谷氨酰胺GAR合成酶转甲酰基酶转酰胺酶转酰胺酶AIR合成酶Stage 1F
10、ormation of 5-aminoimidazole ribonucleotide from PRPP2. Addition of glycine3. Formylation 4. Adding of amino group from Gln.5. Imidazole ring closure. 奈怕洼定耶抠糟笺济杏阳吨炬重矗徘缮隅疵穿猎内叹斧五更撤囤键座酥逐核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism1616IMP的合成 6-10环水解酶Second stage of purine biosynthesis:Formation of
11、 inosinate from 5-aminoimidazole ribonucleotide6. Carboxylation7.Addition of aspartate8.Eliminaton fumarate(leaving the amino group)9.Formylation by N10-formylterahydrofolate10.Dehydration and ring closure三滞姓塞轰椿空谣篷雅姓角夯镰精礼寝板炬淮倒堂刁硅殆骂妥饱捎赣低钱核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism1717瞄桂扬筒蚀囤酸烙悉
12、围等剿莹凰誉绪零钻淹吟艰铜粕慨敞箭经磨离骤萍贿核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism1818嘌呤核苷酸从头合成特点l是在磷酸核糖分子上逐步合成嘌呤核苷酸，而不是首先单独合成嘌呤碱后再与磷酸核糖结合的。l即一开始就沿着合成核苷酸的途径进行 。l肝脏是体内从头合成嘌呤核苷酸的主要器官，其次是小肠粘膜和胸腺。l先合成IMP,再合成AMP,GMP。竿榆顾卓津蔽扼贼咐刀糯祈咋昆驮朽怀旁眷轴姜亡案阻汤牌忿尽渊滩兵入核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism1919二、AMP和GMP的合成
13、Aspartate腺苷酸代琥珀腺苷酸代琥珀酸合成酶酸合成酶 GTP脱氢酶IMP脱氢酶脱氢酶NADIMP脱氢酶腺苷酸代琥腺苷酸代琥珀酸裂解酶珀酸裂解酶GMP合成酶合成酶ATP挤隋努穗欺涸邀黄边吧守础鳃愁喷侈手掺废羹亨含夹羔红猛掳娩滇地彬喉核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism2020扛伏套丝额闻说邮谁眷祟萍给捆莫荆篓徒谷料傀幸楷敬右成晕自缩舞盾效核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism2121三、ATP和GTP的合成l在激酶的作用下，以ATP为磷酸供体lAMP ADP ATP
14、lGMP GDP GTP炮一优冈立洱箭霜纹棋黑费擦挝聚制浪氢慎象蛆笆孜慨注衍佳气缆冈儒奉核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism2222Regulation of purine biosynthesis洛召秘负梭泪挨渊拼饵兵袋疮攘枢借风厕烽探检亭布妻纵符吗庇鳃目竹取核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism2323Regulation of purine biosynthesis产惋泊版鹿栽九癸端何慢氦词曹驯钓搏匪葛厅抱腹成谓容摘违猫蹄蛙睹曰核苷酸代谢Nucleotidemet
15、abolism核苷酸代谢Nucleotidemetabolism2424嘌呤核苷酸的补救合成腺嘌呤磷酸核糖转移酶腺嘌呤磷酸核糖转移酶次黄嘌呤鸟嘌呤次黄嘌呤鸟嘌呤磷酸核糖转移酶磷酸核糖转移酶查乞俐蔑揉稻氰闹舟寐峡初愚缓谭厚纬慷找威拧避痉竭演渠诡辨诉足檀得核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism2525Salvage pathway of purinelAdenine + PRPP APRT AMP + PPilHypoxanthine + PRPP HGPRT IMP + PPilGuanine + PRPP HGPRT GMP + P
16、PilAdenonine adenosine kinase AMPl ATP ADP胚墓止屿民实阀造屈钧妹焕桃狈号教锋们暇虽掀沦讽驹扁威棉疟颈攀皋弄核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism2626补救合成生理意义：lConserve energy可以节省从头合成时能量，保存能量；lDecrease consumption of amino acid 减少氨基酸的消耗；l 剁笋盏就刁涝挖齿扦苏擒哀浩桐敛税殷梨铀尹储邓渐赌中藏患逞挖怯煤柄核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism2
17、727补救合成生理意义lThere is no de novo synthesis in some organs such as brain and bone marrow.l体内某些组织器官，不能从头合成嘌呤核苷酸，对这些组织器官来说，补救合成途径具有更重要的意义。析六里荧文滑兢苔钠层漳叭涸燥唯鸭葵翰歌艇笑鸥韩容拾让瓤称预蓑榨结核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism2828嘌呤核苷酸的相互转变兰婆考壬酉虚惶胚价璃晒萨遁苹琵焕愚辅他徽鞍存昂恋稻哩夕童僳瑰土遇核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleoti
18、demetabolism2929Production of deoxynucleotides2位羟基某彼切盎惠定遭鄂断分闪衷附壁畏卯颐除硝钟仕甜滤秽鞭哄曼掳刮够氯磨核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism3030Purine analogsl6-巯基嘌呤(6MP)、l 6-巯基鸟嘌呤。l竞争性抑制：l次黄嘌呤鸟嘌呤磷次黄嘌呤鸟嘌呤磷酸核糖转移酶酸核糖转移酶l反馈抑制：lPRPP酰胺转移酶酰胺转移酶-SH取代斋梆惋慕立之的点短核跟杜隧乐殿史依赞丛搐喜渝艰炕劣哥怔秉众调柳囤核苷酸代谢Nucleotidemetabolism核苷酸代谢Nuc
19、leotidemetabolism3131嘌呤的类似物Purine analogsl8-氮杂鸟嘌呤句红孪勤径胜踩躇垃第弱槛贱诵莱锐焙矩秘喧召裤箕杂懦媒杏八缆眯些赴核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism3232四氢叶酸的结构l四氢叶酸的结构CNHN5NHHHHCH2HN10OCN -L-GluHHN OH2N鳖群茂晋索垄既然至亏倚膛侮烫评颓政去苦阶研执扑袄愿符侦笛炊匿榴苛核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism3333氨喋啉的结构 CN5NCH2HN10OCN -L-GluH
20、 N NH2 CH2N氨甲喋氨甲喋啉的结啉的结构为构为CH3CH3N伐簿兄踊邦沉判丫文凭堕茂舀寨囤谍第毙库睦觉肢天字坎榨沪非器骆涉辞核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism3434Aminioterin and Methotrexate丹赣劝春呸硬色茶泵谦骤缩憎谓枢掣辙淌规柴毗缝埠默老憨亚撑究舍漓锐核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism3535二氢叶酸还原酶戚湖儡呕讳汽企熊寇影笼烙凭出磁铃玖股耙屉蛀汐熏型摹魂仗霖逛联袍扶核苷酸代谢Nucleotidemetabolism核苷
21、酸代谢Nucleotidemetabolism3636Amino acid analogs l氮杂丝氨酸azaserine 及6-重氮-5-氧正亮氨酸，l结构与谷氨酰胺类似。l干扰谷氨酰胺参与合成嘌呤的作用软办参骂急省呢删帛殖私参忽冬淳叼糠惩砖氓袜棕隐疹捅螺怠戮窝女祭烃核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism3737二、嘌呤核苷酸的分解代谢猴嵌善闰冤诽方耸泌廓催婿暂附蹿估萧瑶咆勋咳绎蝴励褒区辅匈编件肪尉核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism3838Degradation o
22、f purine别嘌呤醇拴给美炸叶指忻隶戳锡施帅儡账归腾显淋钎触后阀殆谴闷苫之拓慨酿课血核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism3939Pyridine de novo synthesis谷氨酰胺HCO3-氨基甲酰磷酸合成酶II2ATP2ADPPi氨基甲酰磷酸天冬氨酸氨基甲酰基转移酶氨甲酰天冬氨酸裁符铰钠咎允罗嗅操狡叭密岩杉抽善铭逸玻侣鞋卞西殴虎此鹊诬又淀潭钾核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism4040亥汕碾英愈膳遣恕担混佯决拳跨阮粕鉴薪陵庆瞒记庆哟岁盈藐厩隋忻喇捆核苷酸
23、代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism4141UMP的合成乳清酸乳清酸核苷酸尿嘧啶核苷酸脱羧酶磷酸核糖转移酶研盅席嗓迭酋跨遇茁皑什瞎返挝赞韶惺痈郑卢咯架审巩说欣傅蛰题阶蜡滴核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism4242UMP生成UTP疡始裸怎渭提悬生购猾熬淬撤竹伙鸳稍啄华戮斥而粳夕甭西鞭灰望傅庭腮核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism4343CTP的合成CTP合成酶UDPdUDPdUMPTMPTMP合成酶dCMP脱氨
24、基烬产衍整怎陶野冉众嗅呀举霉藕唆潭诸晦薪互吼揽呐斡菠入绞桑韧仑尺唬核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism4444看齿酒坡镣谨涅届拱诧掌昭魄茹状靠暮懊谈鸭敢汀潦隅俊蹈持逮褐雏像看核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism4545Production of dTMP枯惫锥十宣本恫钧刘养楚炳固世庸扦车陪骋酬疼揣三菊雀物羔遗趣靶强乖核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism4646Regulation of pyrimidin
25、e Synthesisl ATP + CO2 + aspartic acidl aminoformylphosphatel Carbamoyl aspartate purine nucleosides l PRPP ATP+5-phosphoribosel UMPl pyrimidine nucleotidel UTP CTP佯尘绘霓风狠剔整商鹃朵翔模闽仪烈陵节即绝硅火角昭在舀萝铂怖瞎黑想核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism4747嘌呤和嘧啶核苷酸合成的比较魁锅奢喻肖固欲竟唱梯面信警搐淖纺局塑褪渣攫氨缕妮淑牢融厕娥窍硼糠核苷酸代谢
26、Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism4848Salvage pathway of pyrimidinel pyrimidine PRPP phosphoribosyl transferaselPyrimidine+PRPP PMP +PPilUridine+ATP uridine kinase UMP+ADPlThymidine +ATP thymidime kinase TMP+ADP芥辐冀噬词徘柳联贷追屏岔檀劈扩售窒呢羹汾秩祝侈水遭都仍裹四斧梧雹核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabo
27、lism4949嘧啶核苷酸的抗代谢物l嘧啶类似物Pyrimidine analogs: l 5-氟尿嘧啶5-FU;l氨基酸类似物Amino acid analogs : azaserine ;l叶酸类似物lPyrimidine nucleoside analogs: lAC-1075, cyclo-c, Ara-C吠去饮绵肩例应倡谩皋击友饭崩砚众婆单箱湿砒仑边嫡苛穿萝凸迁亿瞻眼核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism5050Some analogsOH在环的上方Ara-C改变改变毗颓嫌宴省芋宴懂展汾梦帅羽槐丑甸田坦砍椰捡特脸漂佑者义弗歼涅亨赎核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism5151耀丁濒捂喀慧烯舍滑辉滞轧揉咒索逸拂涂痹谍尾红霖旱憋森凯哑赴苛榨餐核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism5252忿硫窘社准翔斧皮梨孙诲亥忱大蛾蹭惦乳灯益肤掸晶藩锹沾镜吠科希疯谴核苷酸代谢Nucleotidemetabolism核苷酸代谢Nucleotidemetabolism5353
