,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,#,糖原,糖异生,糖酵解,糖原合成,糖原降解,葡萄糖,5-,磷酸核糖,柠檬酸循环,氨基酸,乙酰,CoA,乳酸,丙酮酸,葡萄糖,-6-,磷酸,磷酸戊糖途径,葡萄糖的代谢去向,1,糖原,(,红色或红紫色,)2,细胞核,1,2,糖 原,肝细胞中的糖原颗粒,Glycogen granules in a hepatocyte.,Metabolism as a three-dimensional meshwork,一、动物体内糖原的代谢,The Metabolism of Glycogen in Animals,1,、,糖原磷酸化酶,催化糖原的降解,Glycogen Breakdown Is Catalyzed by Glycogen Phosphorylase,糖原磷酸化酶,非还原端,葡萄糖,-1-,磷酸,糖原结合部位,催化部位,别构效应物结合部位,磷酸化部位,兔肌糖原磷酸化酶的模式图,磷酸吡哆醛部位,Glycogen breakdown near an(,1,6)branch point,从非还原端开始,直到距分支点四个葡萄糖处,葡萄糖,-1-,磷酸进入糖酵解或补充血糖,脱支酶是双功能酶,转移酶活性：转移三个葡萄糖残基,(,分支点,邻近非还原末端,)(,1,4),葡,(,萄,),糖苷酶活性,(,16),糖原磷酸化酶,脱支酶,糖原脱支酶,糖原脱支酶,催化的反应,葡萄糖磷酸变位酶催化的反应,Reaction catalyzed by phosphoglucomutase,葡萄糖磷酸变位酶,葡萄糖,-1-,磷酸,葡萄糖,-1,6-,二磷酸,葡萄糖,-6-,磷酸,反应开始于酶上丝氨酸残基的磷酸化,肝脏细胞内质网上的葡萄糖,-6-,磷酸酶催化葡萄糖,-6-,磷酸水解,毛细血管,葡萄糖转运蛋白,质膜,The role of sugar nucleotides in the biosynthesis of glycogen and many other carbohydrate derivatives was first discovered by the Argentine biochemist Luis Leloir.,2,、磷酸核糖,UDP-,葡萄糖,为糖原合成提供葡萄糖,The Sugar Nucleotide UDP-Glucose Donates Glucose for Glycogen Synthesis,糖基的直接供体形式,蔗糖：,UDPG,淀粉：,ADPG,（,UDPG,）,纤维素：,NDPG,果胶：,UDPG,糖核苷酸,的形成,Formation of a sugar nucleotide,亲核攻击,Net reaction:,Sugar phosphate+NTP,NDP-sugar+2Pi,NDP-,糖焦磷酸化酶,焦磷酸酶,3,、糖原合成,Glycogen synthesis,糖原合酶,n,个残基的糖原链的非还原端（,n,4,）,非还原端,4,、糖原分支的合成,Branch synthesis in glycogen,糖原分支酶,glycogen-branching enzyme(amylo(1,4)to(1,6)transglycosylase,糖原分支酶,转移,7,个残基,两分支点至少相距,4,个糖残基,5,、糖原蛋白,催化糖原合成所需引物,Glycogenin Primes the Initial Sugar Residues in Glycogen,Muscle,Glycogenin structure,(,二聚体,),肌肉糖原蛋白,(,生糖蛋白,),结构,UDP-glucose,Tyr,194,residues,Mn,2+,ion,Asp162,Glycogenin(,糖原蛋白,生糖蛋白,)and the structure of the glycogen(,糖原,)particle,葡,(,萄,),糖基转移酶活性,链延伸活性,利用半乳糖合成糖原,UDP-,葡萄糖焦磷酸化酶,糖原合酶,糖原分支酶,糖原合成的酶,Gerty Coris laboratory,around 1947,Carl and Gerty Cori:Pioneers in Glycogen Metabolism and Disease,糖原代谢和疾病的先驱,the metabolism of glycogen,1925 1950,Carl F.Cori and Gerty T.Cori(husband and wife),Cori cycle,The Nobel Prize in Physiology or Medicine 1947,Carl Ferdinand Cori,Gerty Theresa Cori,n,e Radnitz,Bernardo Alberto Houssay,1/4 of the prize,1/4 of the prize,1/2 of the prize,USA,USA,Argentina,Washington University St.Louis,MO,USA,Washington University St.Louis,MO,USA,Instituto de Biologia y Medicina Experimental(Institute for Biology and Experimental Medicine)Buenos Aires,Argentina,b.1896(in Prague,then Austria)d.1984,b.1896(in Prague,then Austria)d.1957,b.1887d.1971,人类糖原储存过多引起的疾病,二、糖原代谢的调节,Coordinated Regulation of Glycogen Synthesis and,Breakdown,别构调节,共价修饰调节,酶促级联调节,糖原磷酸化酶,和糖原合酶,激素对糖原代谢的影响,胰高血糖素,肾上腺素,胰岛素,依赖于,cAMP,的蛋白激酶系统,磷蛋白磷酸酶,-1,系统,(PP1),糖原磷酸化酶,AMP,激活、,ATP,抑制,糖原合酶,AMP,抑制、,ATP,激活,肌肉,糖原磷酸化酶,的共价修饰,Regulation of muscle glycogen phosphorylase by covalent modification,磷酸化酶激酶,磷酸化酶磷酸酶,肾上腺素,胰高血糖素,共价修饰,糖原合成酶,糖原磷酸化酶,共价修饰,蛋白激酶,磷蛋白磷酸酶,磷酸化酶磷酸酶,磷酸化酶激酶,共价修饰,激素调节,肾上腺素和胰高血糖素作用的级联调节机制,Cascade mechanism of epinephrine and glucagon action,Epinephrine,肾上腺素,Glucagon,胰高血糖素,Myocyte,肌细胞,Hepatocyte,肝细胞,Adenylyl cyclase,腺苷酸环化酶,PKA(protein kinase A),蛋白激酶,A,phosphorylase,b,kinase,磷酸化酶激酶,Glycogen phosphorylase,b,糖原磷酸化酶,Glycogen,糖原,Glucose 1-phosphate,葡萄糖,-1-,磷酸,Glycolysis,糖酵解,Muscle contraction,肌肉收缩,Glucose,葡萄糖,糖原代谢的激素控制,肾上腺素,胰高血糖素,肾上腺素,胰岛素,糖原合成,糖原降解,-,肾上腺素能受体,-,肾上腺素能受体,胰岛素,脂质的合成,脂质的分解,蛋白质的合成,糖异生,糖原合成,糖酵解,主动运输,糖原磷酸化酶的激活和糖原合酶的失活,肾上腺素,胰高血糖素,糖原合酶的激活和糖原磷酸化酶的失活,胰岛素,肝脏中葡萄糖对糖原代谢的调节,Regulation of glycogen metabolism by glucose in the liver,三、淀粉和蔗糖的生物合成,Biosynthesis of Starch and Sucrose,ADP-,葡萄糖,是植物质体,淀粉,合成和细菌,糖原,合成的底物,UDP-,葡萄糖,是叶片细胞胞液,蔗糖,的合成底物,淀粉合成,Starch synthesis,ADP-,葡萄糖焦磷酸化酶,淀粉合酶,淀粉合成,Starch synthesis,蔗糖合成,Sucrose synthesis,蔗糖,-6-,磷酸合成酶,蔗糖,-6-,磷酸磷酸酶,果糖,-2,6-,二磷酸是蔗糖合成的调节因子,Fructose 2,6-bisphosphate as regulator of sucrose synthesis,光合作用,暗中,TP,、,Pi,TP,、,Pi,PFK2,、,FBPase2,PFK2,F-2,，,6-BP,F-2,，,6-BP,PFK1,FBPase1,F-6-P,F-1,，,6-BP,蔗糖合成,EMP,Intracellular Second Messengers*,Messenger,Source,Effect,cAMP,Adenylyl cyclase,Activates protein kinases,cGMP,Guanylyl cyclase,Activates protein kinases,regulates ion channels,regulates phosphodiesterases,Ca,2+,Ion channels in ER andplasma membrane,Activates protein kinases,activates Ca,2+,-modulated proteins,IP,3,PLC action on PI,Activates Ca,2+,channels,DAG,PLC action on PI,Activates protein kinase C,Phosphatidic acid,Membrane component and product of PLD,Activates Ca,2+,channels,inhibits adenylyl cyclase,Ceramide,PLC action onsphingomyelin,Activates protein kinases,Nitric oxide(NO),NO synthase,Activates guanylyl cyclase,relaxes smooth muscle,Cyclic ADP-ribose,cADP-ribose synthase,Activates Ca,2+,channels,*IP,3,is inositol-1,4,5-trisphosphate;PLC is phospholipase C;PLD is phospholipase D;PI is phosphatidylinositol;DAG is diacylglycerol.,第九章 糖的生物合成,某些时候，在绿色植物中同时存在着循环的电子传递与非循环的电子传递途径，循环的电子传递途径能否产生,ATP,、,O,2,、或,NADPH,？,从葡萄糖,-6-,磷酸合成糖原所需的能量是否等同于糖原降解为葡萄糖,-6-,磷酸需要的能量？,