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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
25、 conformation. ATP & glucose-6-phosphate, which both have binding sites that overlap that of AMP, inhibit Phosphorylase, promoting the tense conformation. Thus glycogen breakdown is inhibited when ATP and glucose-6-phosphate are plentiful.,Allosteric regulation,35,糖原磷酸化酶 a 对Glc敏感：结合在其别构部位的Glc可诱发构象变化
26、，使被磷酸化的Ser残基暴露于磷酸化酶 a 磷酸酶的作用下，后者可将高活性的磷酸化酶 a 转变成低活性的磷酸化酶 b 以适应高血糖, 糖原磷酸化酶的别构调节,血糖升高,R state (Arg569),T state (Asp238),Glycogen Synthase is allosterically activated by glucose-6-P (opposite of effect on Phosphorylase). Thus Glycogen Synthase is active when high blood glucose leads to elevated intrace
27、llular glucose-6-P. It is useful to a cell to store glucose as glycogen when the input to Glycolysis (glucose-6-P), and the main product of Glycolysis (ATP), are adequate.,磷酸化酶和糖原合酶的活性是受磷酸化或去磷酸化的共价修饰的调节。两种酶磷酸化及去磷酸化的方式相似，但其效果相反。,38, 糖原磷酸化酶的共价修饰,胰高血糖素,肾上腺素,- 在高活性的磷酸化酶 a中，各亚基的特定Ser14残基均被磷酸化 - 被磷酸化酶 a磷酸
28、酶去磷酸化后即转变为低活性的磷酸化酶 b (失活)；后者可经由磷酸化酶 b激酶的磷酸化作用而被重新激活 - 糖原合酶的共价修饰与之相似但活化形式相反，故磷酸化时糖原分解加速而糖原合成被抑制(合酶 a 低活性)，去磷酸化时则分解被抑制而合成加速 (合酶 b高活性),41, 蛋白质(酶)的磷酸化与去磷酸化,- 对已有酶分子进行共价修饰 的调节作用通常要快得多,- 其他共价修饰如腺苷酰化、 甲基化、糖基化和酯化等,- 蛋白激酶通常与相应的磷酸 蛋白磷酸酶配套作用(复原),- 和酶调节相似，共价修饰 也常常由某些细胞外信号所 触发，例如激素和生长因子,真核类1/2的蛋白质在某些条件下均可磷酸化,血糖浓
29、度一般在80-120mg/100ml，称为葡萄糖耐量。血糖低于70或过度兴奋可刺激延脑第四脑室“糖中枢”，引起肝糖原分解。下丘脑可分泌皮质释放因子，作用于肾上腺皮质，升高血糖。影响糖代谢的激素有：,1.胰岛素：由胰岛细胞分泌，促进糖原合成酶活性，诱导葡萄糖激酶合成，加强磷酸果糖激酶作用。通过加速糖原合成和糖酵解降低血糖效应。 2.肾上腺素和胰高血糖素：通过cAMP激活糖原磷酸化酶，诱导肝中磷酸烯醇式丙酮酸羧化激酶和果糖二磷酸酶的合成，促进异生，升高血糖。,Regulation by covalent modification (phosphorylation): The hormones gl
30、ucagon and epinephrine activate G-protein coupled receptors to trigger cAMP cascades. Both hormones are produced in response to low blood sugar. Glucagon, which is synthesized by a-cells of the pancreas, activates cAMP formation in liver. Epinephrine activates cAMP formation in muscle.,The cAMP casc
31、ade results in phosphorylation of a serine hydroxyl of Glycogen Phosphorylase, which promotes transition to the active (relaxed) state. The phosphorylated enzyme is less sensitive to allosteric inhibitors. Thus, even if cellular ATP & glucose-6-p are high, Phosphorylase will be active. The glucose-1
32、-p produced from glycogen in liver may be converted to free glucose for release to the blood. With this hormone-activated regulation, the needs of the organism take precedence over needs of the cell.,Commonly used terminology: “a“ is the form of the enzyme that tends to be active, and independent of
33、 allosteric regulators (in the case of Glycogen Phosphorylase, when phosphorylated). “b“ is the form of the enzyme that is dependent on local allosteric controls (in the case of Glycogen Phosphorylase when dephosphorylated).,Insulin, produced in response to high blood glucose, triggers a separate si
34、gnal cascade that leads to activation of Phosphoprotein Phosphatase. Thus insulin antagonizes effects of the cAMP cascade induced by glucagon & epinephrine.,cAMP结构,第二信使(second messenger)： 响应外部信号（第一信使），例如激素在细胞内合成的效应分子，例如cAMP、肌醇三磷酸（IP3）或二酰基甘油等。第二信使再去调节靶酶，引起细胞内各种效应。 激素通过cAMP促进磷酸化作用，使磷酸化酶成为a型（有活性），合成酶变成
35、b型（无活性）。合成酶由蛋白激酶磷酸化。,激素通过cAMP-蛋白激酶调节代谢示意图,内在蛋白质的磷酸化作用,改变细胞的生理过程,细胞膜,细胞膜,蛋白激酶 （无活性）,蛋白激酶（有活性）,受体,非磷酸化蛋白激酶,级联放大(cascade)： 在体内的不同部位，通过一系列的酶促反应来传递一个信息，并且初始信息在传到系列反应的最后时，信号得到放大，这样的一个系列叫做级联系统。最普通的类型是蛋白水解和蛋白质磷酸化的级联放大。 G蛋白(G proteins)： 在细胞内信号传导途径中起着重要作用的GTP结合蛋白质，由、三个不同亚基组成。与激素受体结合的配体诱导GTP与G蛋白结合的GDP进行交换，结果激活
36、位于信号传导途径中下游的腺苷酸环化酶。G蛋白将胞外的第一信使肾上腺素等激素和胞内的腺苷酸环化酶催化的腺苷酸环化生成的第二信使cAMP联系起来。G蛋白具有内源GTP酶活性。, 肾上腺素和胰高血糖素作用的级联反应机制,- 两者分别结合于肌细胞和 肝细胞外表的特殊受体而 激活GTP结合蛋白Gs,级联放大反应,- 最终导致糖原降解进而 提供能量(肌肉)和升高 血糖(肝脏),肌细胞,肝细胞,no G6Pase,由于酶的共价修饰反应是酶促反应，只要有少量信号分子（如激素）存在，即可通过加速这种酶促反应，而使大量的另一种酶发生化学修饰，从而获得放大效应。这种调节方式快速、效率极高。,56, 丙酮酸激酶的调节
37、,前馈激活,反馈抑制,蛋白激酶 A,蛋白磷酸酶,脊椎动物至少发现有三种同工酶，分别存在于肝脏(L)和肌肉(M)等肝外组织,-,低血糖,将Glc调剂给大脑等组织,57,- F-2,6-BP为PFK-1和FBPase-1 的别构效应剂，可同时介导反向 调节以加速糖酵解而抑制糖异生,果糖二磷酸酶-1,磷酸果糖激酶-1, F-2,6-BP是糖酵解和糖异生的高效调节剂,58,- F-2,6-BP仅为调节剂，浓度 取决于其形成和降解的速率,磷酸果糖激酶-2,果糖二磷酸酶-2,Bifunctional Enz,- PFK-2和FBPase-2分别是 同一双功能蛋白的两个不 同活性区，同时受胰岛素 和胰高血糖
38、素的反向调节,糖尿病,糖尿病 （diabetes）是由遗传因素、免疫功能紊乱、精神因素等等各种致病因子作用于机体，导致胰岛功能减退、胰岛素抵抗等而引发的糖、蛋白质、脂肪、水和电解质等一系列代谢紊乱综合征，临床上以高血糖为主要特点，典型病例可出现多尿、多饮、多食、消瘦等表现，即“三多一少”症状。 糖原合成减少； 糖异生作用加强； 葡萄糖转化为6磷酸葡萄糖减弱； 糖酵解和三羧酸循环减弱； 肌肉和脂肪组织中葡萄糖进入细胞膜减弱。,低血糖症(Hypoglycemia),血糖低于6070mg/100ml； 原因：胰岛素分泌过多或治疗上胰岛素使用过量、肾上腺皮质和脑下垂体机能减退、长期不能进食或有严重肝脏
39、疾患者； 脑组织对低血糖比较敏感，当血糖浓度低于45时，严重影响脑组织的机能，会发生“低血糖休克”或“低血糖昏迷”。,Symptoms in addition to excess glycogen storage: When a genetic defect affects mainly an isoform of an enzyme expressed in liver, a common symptom is hypoglycemia, relating to impaired mobilization of glucose for release to the blood during
40、fasting. When the defect is in muscle tissue, weakness & difficulty with exercise result from inability to increase glucose entry into Glycolysis during exercise. Additional symptoms depend on the particular enzyme that is deficient.,Glycogen Storage Diseases are genetic enzyme deficiencies associat
41、ed with excessive glycogen accumulation within cells.,A genetic defect in the isoform of an enzyme expressed in liver causes the following symptoms: After eating a CHO meal, elevated blood levels of glucose, lactate, & lipids. During fasting, low blood glucose & high ketone bodies. Which liver enzym
42、e is defective? Explain Symptoms: After eating, blood glucose is high because liver cannot store it as glycogen. Some excess glucose is processed via Glycolysis to produce lactate & fatty acid precursors. During fasting, glucose is low because the liver lacks glycogen stores for generation of glucos
43、e. Ketone bodies are produced as an alternative fuel.,Glycogen Synthase,Question: How would you nutritionally treat deficiency of liver Glycogen Synthase? Frequent meals of complex carbohydrates (avoiding simple sugars that would lead to a rapid rise in blood glucose) Meals high in protein to provid
44、e substrates for gluconeogenesis.,二、糖异生,1、糖异生作用的主要途径和关键反应 2、葡萄糖代谢与糖异生作用的关系 3、糖异生的总反应式和调控,糖异生是指由非糖物质例如乳酸、氨基酸、甘油等作为原料合成葡萄糖的作用。葡糖异生作用对于机体饥饿时和激烈运动时不断提供葡萄糖维持水平是非常重要的。脑和红细胞几乎全部依赖血糖提供能源。葡糖异生作用的绝大多数酶是细胞溶胶酶，只有丙酮酸羧化酶和葡萄糖 -6- 磷酸酶除外，前者位于线粒体基质，后者结合在光面内质网上。,用整体动物做实验，禁食24小时，大鼠肝脏中的糖原由7%降低到1%，饲喂乳酸、丙酮酸或三羧酸循环代谢的中间物后可以
45、使大鼠肝糖原增加。 根皮苷是一种从梨树茎皮中提取的有毒的糖苷，它能抑制肾小管将葡萄糖重吸收进入血液中，这样血液中的葡萄糖就不断的由尿中排出。当给用根皮苷处理过的动物饲喂三羧酸循环中间代谢物或生糖氨基酸后，这些动物尿中的糖含量增加。 糖尿病人或切除胰岛的动物，他们从氨基酸转化成糖的过程十分活跃。当摄入生糖氨基酸时，尿中糖含量增加。,糖异生的证据如下：,糖异生途径的前体,1、凡是能生成丙酮酸的物质都可以变成葡萄糖。例如三羧酸循环的中间物，柠檬酸、异柠檬酸、-酮戊二酸、琥珀酸、延胡索酸和苹果酸都可以转变成草酰乙酸而进入糖异生途径。,2、大多数氨基酸是生糖氨基酸如丙氨酸、谷氨酸、天冬氨酸、丝氨酸、半胱
46、氨酸、甘氨酸、精氨酸、组氨酸、苏氨酸、脯氨酸、谷胺酰胺、天冬酰胺、甲硫氨酸、缬氨酸等，它们可转化成丙酮酸、-酮戊二酸、草酰乙酸等三羧酸循环中间物参加糖异生途径。,但是这种转变不是糖分解代谢的简单逆转，必须克服那些由关键酶所催化的不可逆反应造成的“能障”。主要有三个酶催化的反应, 异生过程必须设法“绕过”这三个反应.,糖异生作用的总反应式如下： 2丙酮酸+4ATP+2GTP+2NADH+2H+4H2O 葡萄糖+2NAD+ +4ADP +2GDP +6Pi,糖异生主要途径 和关键反应,非糖物质转化成糖代谢的中间产物后，在相应的酶催化下,绕过糖酵解途径的三个不可逆反应,利用糖酵解途径其它酶生成葡萄糖
47、的途径称为糖异生。,糖原（或淀粉）,1-磷酸葡萄糖,6-磷酸果糖,1，6-二磷酸果糖,3-磷酸甘油醛磷酸二羟丙酮,2磷酸烯醇丙酮酸,2丙酮酸,葡萄糖,己糖激酶,果糖激酶,二磷酸果糖磷酸酶,丙酮酸激酶,丙酮酸羧化酶,6-磷酸葡萄糖磷酸酶,6-磷酸葡萄糖,2草酰乙酸,PEP羧激酶,糖异生途径关键反应之一,PEP羧激酶,丙酮酸羧化酶,磷酸烯醇丙酮酸（PEP）,丙酮酸,草酰乙酸,1、丙酮酸羧化生成磷酸烯醇式丙酮酸,丙酮酸+ATP+GTP 磷酸烯醇式丙酮酸+ADP+GDP,草酰乙酸不能自由进出线粒体膜，因此需要穿梭机制。,丙酮酸羧化酶（线粒体酶）,以生物素(biotin)作为辅基。生物素起CO2载体的作
48、用。生物素的末端羧基与酶分子的一个赖氨酸残基的-氨基以酰胺键相连。,Biotin has a 5-C side chain whose terminal carboxyl is in amide linkage to the e-amino group of an enzyme lysine. The biotin & lysine side chains form a long swinging arm that allows the biotin ring to swing back & forth between 2 active sites.,Pyruvate Carboxylase
49、uses biotin as prosthetic group.,苹果酸-草酰乙酸穿梭作用,细胞液,线粒体内膜体,天冬氨酸,-酮戊二酸,苹果酸,草酰乙酸,谷氨酸,-酮戊二酸,天冬氨酸,苹果酸,谷氨酸,NADH+H+,NAD+,草酰乙酸,NAD+,线粒体基质,NADH+H+,（、 、 、 为膜上的转运载体）,呼吸链,Phosphofructokinase (Glycolysis) catalyzes: fructose-6-P + ATP fructose-1,6-bisP + ADP Fructose-1,6-bisphosphatase (Gluconeogenesis) catalyzes: fructose-1,6-bisP + H2O fructose-6