《生物化学—代谢篇》第二十六章 糖原的分解与合成

第26章 糖原的分解与合成 Degradat ion and Synthesis of Glycogen

第 26 章 糖原的分解与合成 Degradation and Synthesis of Glycogen

糖原的分解代谢 1. Glycogen in cells is first converted to Glc-6-P for oxidative degradation ★糖原磷酸化酶作用于糖原的非还原性末端, 经磷酸解作用,产生Gc-1-P。 ★糖原磷酸化酶的辅基磷酸吡哆醛直接作用 于(α-1,4)糖苷键 ★在距分支点四个糖单位处,糖原磷酸化酶 停止磷酸解作用

一、糖原的分解代谢 1. Glycogen in cells is first converted to Glc-6-P for oxidative degradation: ★ 糖原磷酸化酶作用于糖原的非还原性末端， 经磷酸解作用，产生 Glc-1-P 。 ★ 糖原磷酸化酶的辅基磷酸吡哆醛直接作用 于(a-1,4) 糖苷键。 ★ 在距分支点四个糖单位处，糖原磷酸化酶 停止磷酸解作用

★转移酶( a bifunctional debranching enzyme)(160kD)转移一个分支点的三个 糖单位到另一个非还原末端,脱枝酶(α 1,6- glucosidase)脱去分支点的葡萄糖。 x Glc-1-P is then converted to Glc-6-p by the catalysis of phosphoglucomutase, which uses glucose 1, 6-bisphosphate as both a cofactor and an intermediate an ser residue on the enzyme facilitates the phosphorylation cycle Glc-6-P is further degraded via the glycolysis pathway(or converted to glucose in liver)

★ 转移酶（ A bifunctional debranching enzyme ） (160 kD)转移一个分支点的三个 糖单位到另一个非还原末端， 脱枝酶（ a- 1,6- glucosidase ）脱去分支点的葡萄糖。 ★ Glc-1-P is then converted to Glc-6-P by the catalysis of phosphoglucomutase, which uses glucose 1,6-bisphosphate as both a cofactor and an intermediate. An Ser residue on the enzyme facilitates the phosphorylation cycle. ★ Glc-6-P is further degraded via the glycolysis pathway (or converted to glucose in liver)

2. The glycogen phosphorylase isozymes in muscle and liver are regulated and differently ◆肌糖原和肝糖原的生理功能不同:前者主要是 氧化供能( oxidative degradation to generate ATP for muscle),而肝糖原主要用于维持血 糖浓度( producing and exporting glucose when in demand and importing and storing When in excess ◆肌糖原磷酸化酶和肝糖原磷酸化酶为同工酶 者的活性均受磷酸化(cata! yzed by specific phosphorylase b kinase)和脱磷酸 catalyzed by specific phosphorylase a phosphatase)共价可逆调控

2. The glycogen phosphorylase isozymes in muscle and liver are regulated and differently ◆肌糖原和肝糖原的生理功能不同：前者主要是 氧化供能（ oxidative degradation to generate ATP for muscle ），而肝糖原主要用于维持血 糖浓度（producing and exporting glucose when in demand and importing and storing when in excess）. ◆ 肌糖原磷酸化酶和肝糖原磷酸化酶为同工酶， 二者的活性均受磷酸化（ catalyzed by specific phosphorylase b kinase ）和脱磷酸 （ catalyzed by specific phosphorylase a phosphatase ）共价可逆调控

The phosphorylase b kinases in muscle and liver are controlled by two different hormones, epinephrine(肾上腺素)and g! ucagon(胰增血糖素) respectively.D High level of amp binds to and activates the b form of the muscle isozyme which is blocked by a high level of aTp High level of glucose binds to the a form of the liver isozyme exposing the phosphorylated ser residues to the action of phosphorylase a phosphatase and converting it to the less active b form

◆ The phosphorylase b kinases in muscle and liver are controlled by two different hormones, epinephrine (肾上腺素) and glucagon(胰增血糖素) respectively. • ◆ High level of AMP binds to and activates the b form of the muscle isozyme, which is blocked by a high level of ATP. • ◆ High level of glucose binds to the a form of the liver isozyme, exposing the phosphorylated Ser residues to the action of phosphorylase a phosphatase and converting it to the less active b form

糖原的合成代谢 1. Glycogen is synthesized using UDP-glucose: ◆6-磷酸葡萄糖( from glucose phosphorylation or gluconeogenesis)首先 转化为1-磷酸葡萄糖(cata/ yzed by phosphoglucomutase),然后与UTP反应形 成 UDP-glucose(UDPG),催化该反应 的是尿嘧啶核苷二磷酸葡萄糖焦磷酸化酧 (UDP-glucose pyrophosphorylase named for the reverse reaction

二、糖原的合成代谢 1. Glycogen is synthesized using UDP-glucose： ◆ 6-磷酸葡萄糖 (from glucose phosphorylation or gluconeogenesis)首先 转化为1-磷酸葡萄糖 (catalyzed by phosphoglucomutase), 然后与UTP反应形 成 UDP-glucose（UDPG） ，催化该反应 的是尿嘧啶核苷二磷酸葡萄糖焦磷酸化酶 (UDP-glucose pyrophosphorylase named for the reverse reaction)

2. Glycogen is extended from the nonreducing end using UDP-glucose ※在糖原合成酶催化下,UDFG中的葡萄糖分子 通过α-1,4糖苷键连接到糖原引物的非还原性末 端 ※分枝的形成由分枝酶催化[ glycosy(4->6)- transferase ] a terminal fragment of 6-7 residues is transferred from a branch having at least 11 residues to the C-6 hydroxyl group at a more interior position of the same or another glycogen chain

2. Glycogen is extended from the nonreducing end using UDP-glucose • ※ 在糖原合成酶催化下，UDPG中的葡萄糖分子 通过a-1,4 糖苷键连接到糖原引物的非还原性末 端。 • ※ 分枝的形成由分枝酶催化［ glycosyl-(4→6)- transferase ］: a terminal fragment of 6-7 residues is transferred from a branch having at least 11 residues to the C-6 hydroxyl group at a more interior position of the same or another glycogen chain

※在没有糖原引物时,糖原的合成是从生 糖原蛋白质开始的。 The very first glucose residue transferred from UDP-glucose, is covalently attached to Tyr 94 of glycogenin (生糖原蛋白质),a37 kDa protein that also catalyzes the assembly of the first 8 glucose residues in a complex formed between glycogenin and glycogen synthase

• ※ 在没有糖原引物时，糖原的合成是从生 糖原蛋白质开始的。 The very first glucose residue, transferred from UDP-glucose, is covalently attached to Tyr194 of glycogenin （生糖原蛋白质）, a 37 kDa protein that also catalyzes the assembly of the first 8 glucose residues in a complex formed between glycogenin and glycogen synthase

3. Glycogen synthase and glycogen phosphorylase are reciprocally regulated in vertebrates by hormones ★糖原磷酸化酶和糖原合成酶的活性均受磷酸化 和脱磷酸( Phosphorylation and dephosphorylation)调控,但作用正好相反 x Hormones like epinephrine(acting on muscle cells) or glucagon(acting on liver cells) will activate protein kinase a, which will lead to phosphorylation modification of both the glycogen phosphorylase(thus activating it and the glycogen synthase(thus inactivating it

3. Glycogen synthase and glycogen phosphorylase are reciprocally regulated in vertebrates by hormones • ★糖原磷酸化酶和糖原合成酶的活性均受磷酸化 和脱磷酸（ Phosphorylation and dephosphorylation ）调控，但作用正好相反。 • ★ Hormones like epinephrine (acting on muscle cells) or glucagon (acting on liver cells) will activate protein kinase A, which will lead to phosphorylation modification of both the glycogen phosphorylase (thus activating it) and the glycogen synthase (thus inactivating it)

Insulin nsulin receptor ranI PI-3K kpIp PIP2-00000005 OH PDK-1 Cytosol IRS-1 L IRS. PKB Activ P GSK3 GSK3 Inactive AIOH Glycogen YP Glycogen Y-OH synthase synthase b Inactive