生物化学ii(苏维恒)chapter13.ppt
《生物化学ii(苏维恒)chapter13.ppt》由会员分享,可在线阅读,更多相关《生物化学ii(苏维恒)chapter13.ppt(117页珍藏版)》请在三一文库上搜索。
1、Chapter13 Additional Pathways in Carbohydrate Metabolism,Glycogen degradation and synthesis 糖原代谢与分解 Gluconeogenesis 糖异生 The pentose Phosphate pathway 磷酸戊糖途径,(一)糖原的分解和生物合成,一、糖原的分解 二、糖原的生物合成 三、糖原代谢的调控,- 糖原是动物和细菌内糖的贮存形式 以颗粒状存在于胞质中 含有合成、降解酶和调节蛋白 糖原贮备的生物学意义:可迅速动用以供急需 (尤其是大脑和红细胞等),- 主要贮存器官:肝脏和肌肉 肝糖原:血糖的主要
2、来源 肌糖原: 肌肉剧烈收缩时供能,Glycogen Functions,糖原( glycogen ),又称动物淀粉,支链,分子量数百万以上。主要由葡萄糖以 (1,4)糖苷键相连(93%),以少量(1,6)糖苷键(7%)形成分支。有肝糖原和肌糖原。,一、糖原的酶促磷酸解, 糖原的结构及其连接方式,磷酸化酶a(催化1.4-糖苷键断裂) 三种酶协同作用: 转移酶(催化寡聚葡萄糖片段转移) 脱支酶(催化1.6-糖苷键水解断裂),-1,4-糖苷键,-1,6糖苷键,非还原性末端,Glycogen is a polymer of glucose residues linked by a(14) glyco
3、sidic bonds, mainly a(16) glycosidic bonds, at branch points. Glycogen chains & branches are longer than shown. Glucose is stored as glycogen predominantly in liver and muscle cells.,Liver Buffer for regulating blood glucose levels Muscle Store of glucose as a fuel for exercise high intensity exerci
4、se dependent on anaerobic glycolysis,Glycogen Degradation,Glycogen Phosphorylase Hydrolyzes glucose units from glycogen Produces glucose-1-P Removal of branch points Debranching enzyme complex Glucan transferase Alpha-1,6-glucosidase,Glycogen Phosphorylase catalyzes phosphorolytic cleavage of the a(
5、14) glycosidic linkages of glycogen, releasing glucose-1-phosphate as reaction product. glycogen(n residues) + Pi glycogen (n1 residues) + glucose-1-phosphate This phosphorolysis may be compared to hydrolysis: Hydrolysis: R-O-R + HOH R-OH + R-OH Phosphorolysis: R-O-R + HO-PO32- R-OH + R-O-PO32-,Glyc
6、ogen catabolism (breakdown):,A glycogen storage site on the surface of the Phosphorylase enzyme binds the glycogen particle. Given the distance between storage & active sites, Phosphorylase can cleave a(14) linkages only to within 4 residues of an a(16) branch point. This is called a “limit branch“.
7、,11,Structure of Glycogen Phosphorylase,monomer (842 AA),dimer,别构剂结合点,糖原颗粒结合位点,催化部位,PLP,- Ionized G1P cant diffuse out of cell - Glc is phosphorylated: no ATP needs to be consumed to permit entry into glycolysis,= removal of a terminal Glc residue from the nonreducing end of a glycogen by glycogen p
8、hosphorylase,1. 糖原分解,- 该过程可重复进 行至离某个分支点相隔4 Glc. - 支链淀粉亦可在淀粉磷酸化酶的作用下以类似的方式降解,Debranching enzyme has 2 independent active sites, consisting of residues in different segments of a single polypeptide chain: The transferase of the debranching enzyme transfers 3 glucose residues from a 4-residue limit bra
9、nch to the end of another branch, diminishing the limit branch to a single glucose residue. The a(16) glucosidase moiety of the debranching enzyme then catalyzes hydrolysis of the a(16) linkage, yielding free glucose. This is a minor fraction of glucose released from glycogen. The major product of g
10、lycogen breakdown is glucose-1-phosphate, from Phosphorylase activity.,14, 糖原脱分支,G1P,phospho- glucomutase,activity 1 = 糖基转移酶,activity 2 = (16)糖苷酶,G6P,- Product of glycogen degradation = G1P (85%) & free Glc (15%) - Debranching enzyme = bifunctional enzyme,磷酸葡糖变位酶,脱支酶,- G6P去路 肝、肾细胞中水解成Glc 脑、肌细胞中直接进入酵
11、解 - 糖原颗粒不会被完全分解, 一般是分支减少/分子变小,Phosphoglucomutase catalyzes the reversible reaction: glucose-1-phosphate glucose-6-phosphate A serine OH at the active site donates & accepts Pi. The bisphosphate is not released. Phosphoglycerate Mutase has a similar mechanism, but instead uses His for Pi transfer., 磷
12、酸葡糖变位酶作用机制,- 该酶需以活性位点的Ser 残基已被磷酸化的形式 参与反应,- 先由酶将其磷酰基转移 给G1P而生成G-1,6-BP,- 再由G-1,6-BP将其C1位 磷酰基转移给酶并释出 G6P,Glucose-6-phosphate may enter Glycolysis or (mainly in liver) be dephosphorylated for release to the blood. Liver Glucose-6-phosphatase catalyzes the following, essential to the livers role in mai
13、ntaining blood glucose: glucose-6-phosphate + H2O glucose + Pi Most other tissues lack this enzyme.,18, 肝糖元降解可以补充血糖,G6P酶仅存在于肝脏和肾脏,为内质网膜上的整合蛋白(可能有九个跨膜螺旋区段),活性点位于腔内侧。,T1/G6P酶的任一遗传缺失均将导致糖原代谢紊乱并最终引发Ia型糖原贮积病,19,- High Pi in cell favors glycogen breakdown & prevents from glycogen synthesis in vivo. - Need
14、s another way to activate Glc for transferring to glycogen chain.,2. 糖原合成,Luis Leloir 1906-1987 1970 NP in Chem.,UDP-Glc,much better leaving group,Glc激活方式不同: - 降解时磷酸解成G1P - 合成时核苷酰化成UDP-Glc,糖原的生物合成,1. UDP-葡萄糖焦磷酸化酶 (UDP-glucose pytophosphorylase) 催化单糖基活化形成糖核苷二磷酸,为各种聚糖形成时,提供糖基和能量。动物细胞中糖元合成时需UDPG;植物细胞中蔗
15、糖合成时需UDPG,淀粉合成时需ADPG,纤维素合成时需GDPG和UDPG。 2. 糖原合酶(glycogen synthase) 催化-1,4-糖苷键合成 3.糖原分支酶 ( glycogen branching enzyme) 催化-1,6-糖苷键合成,As glucose residues are added to glycogen, UDP-glucose is the substrate and UDP is released as a reaction product. Nucleotide diphosphate sugars are precursors also for sy
16、nthesis of other complex carbohydrates, including oligosaccharide chains of glycoproteins, etc.,Uridine diphosphate glucose (UDP-glucose) is the immediate precursor for glycogen synthesis.,22,- 核苷二磷酸糖在寡糖和多糖 的生物合成中作为糖基供体 - UDP-Glc for glycogen synthesis in animals - ADP-Glc for starch synthesis in pl
17、ants and glycogen synthesis in bacteria,= O on the sugar phosphate attacking nucleophilicly P of NTP and displacing PPi, which hydrolysis pulling the reaction forward and irreversibly, 核苷二磷酸糖/糖核苷酸的形成,核苷二磷酸糖焦磷酸化酶,(无机)焦磷酸酶,Go = -2027 kJ/mol,Go 0 kJ/mol,Glycogen Synthase catalyzes transfer of the gluco
18、se moiety of UDP-glucose to the hydroxyl at C4 of the terminal residue of a glycogen chain to form an a(1 4) glycosidic linkage: glycogen(n residues) + UDP-glucose glycogen(n +1 residues) + UDP,A branching enzyme transfers a segment from the end of a glycogen chain to the C6 hydroxyl of a glucose re
19、sidue of glycogen to yield a branch with an a(1 6) linkage.,24, Glycogen synthesis,= glycogen chain elongated by glycogen synthase,transferring the Glc residue from UDP-Glc to the nonreducing end of a glycogen branch to make a new (14) linkage,Go = -13.4 kJ/mol,糖原合酶不能从头开始而将两个游离的UDP-Glc直接连接起来,糖原合成酶将U
20、DP-葡萄糖的糖基加在糖原引物的非还原端葡萄糖的C4羟基上。引物至少要有4个糖基,由糖原生成(起始)蛋白和糖原起始合成酶合成,将UDP-葡萄糖加在引发蛋白的酪氨酸羟基上。,糖原合酶,UDP+(葡萄糖)n+1,UDPG + 引物,26, Muscle Glycogenin(糖原生成蛋白或起始蛋白) (dimer),Tyr194,Asp162,initiates glycogen synthesis. Glycogenin is an enzyme that catalyzes attachment of a glucose molecule to one of its own tyrosine
21、residues. Glycogenin is a dimer.,27, 由糖原生成(起始)蛋白开始的糖原颗粒形成,= 引发蛋白+葡糖基转移酶,葡糖基转移活性,合成酶与糖原合酶结合,糖原合酶活性,合酶与分支酶活性,Glycogen core,葡糖基延长活性,在葡糖基转移酶活性作用下,Tyr194-OH亲核攻击UDP-Glc的C1而生成糖基化的Tyr (非还原末端) 非还原末端Glc的C4-OH对另一UDP-Glc亲核攻击以形成(14)糖苷键 达到8个残基后由糖原合酶继续延长及分支, 糖原生成(起始)蛋白反应机制,-,-,-, Branch synthesis in glycogen,糖原分支酶
22、,糖原分支酶从一段至少有11 Glc残基的分支上转移67个残基给该分支或邻近分支还原端某个残基的C6上以形成新的分支,断裂(14)键,形成(16)键,糖原分支的生物学意义 - 增加糖原的可溶性 - 增加非还原端数量,30,ADP-Glc 焦磷酸化酶, Starch synthesis,淀粉合酶,31,小结:糖原代谢, 糖原以颗粒形式储存于肌肉和肝脏,颗粒中还含有 糖原代谢及调节的各种酶, 糖原磷酸化酶催化糖原链非还原端残基磷酸解断裂 (14)键而生成G1P,去分支酶将分支转移到主链并以游离Glc形式释出(16)分支点残基, 磷酸葡糖变位酶催化G1P和G6P相互转化,后者在 肌细胞中可直接进入酵
23、解,或在肝脏中被内质网的 G6P酶水解成Glc后释出以补充血糖, 在糖原合酶催化下,UDP-Glc将糖基转移到糖原链非 还原端上,分支酶则可在分支点处形成(16)连接, 新糖原合成起始于UDP-Glc的葡糖基与糖原生成起始蛋白的Tyr残基间糖苷键的自我催化形成,随后连续添加7 Glc残基形成引物,后者再由糖原合酶催化延长,32,3. 糖原降解与合成的协同调节,(eg. Hexokinase IV),糖原的合成和分解通过对糖原磷酸化酶和糖原合酶的调节机制进行调控,别构调控,共价修饰,1. 糖原磷酸化酶:AMP(激活); ATP、6-P-G、Glc,2. 糖原合成酶:6-P-G、Glc,Glyco
24、gen Phosphorylase in muscle is subject to allosteric regulation by AMP, ATP, and glucose-6-phosphate. A separate isozyme of Phosphorylase expressed in liver is less sensitive to these allosteric controls. AMP (present significantly when ATP is depleted) activates Phosphorylase, promoting the relaxed
- 配套讲稿:
如PPT文件的首页显示word图标,表示该PPT已包含配套word讲稿。双击word图标可打开word文档。
- 特殊限制:
部分文档作品中含有的国旗、国徽等图片,仅作为作品整体效果示例展示,禁止商用。设计者仅对作品中独创性部分享有著作权。
- 关 键 词:
- 生物化学 ii 苏维恒 chapter13
链接地址:https://www.31doc.com/p-3061388.html