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Pentose phosphate PathwayPentose phosphate Pathway
Chapter 20.4Chapter 20.4
GlycolysisGlycolysis
中間代謝物中間代謝物
TransketolaseTransketolase
轉酮醇酶轉酮醇酶
TPP 為 transketolase 的輔基
接收 aldose
得到重組的 ketose
TransaldolaseTransaldolase
轉醛醇酶轉醛醇酶
TransaldolaseTransaldolase
上的上的 LysLys
脫水脫水 質子化質子化
去質子化去質子化
TransketolaseTransketolase
轉酮醇酶轉酮醇酶
TransaldolaseTransaldolase
轉醛醇酶轉醛醇酶
磷酸五碳糖的四個代謝模式磷酸五碳糖的四個代謝模式
取決於取決於 NADPHNADPH 、、 Ribose-5-PRibose-5-P 、、 ATPATP
GycolysisGycolysis
當當 NADPHNADPH 需要量需要量 < Ribose-5-P< Ribose-5-P 需要量需要量
5 G-6-P + ATP5 G-6-P + ATP  6 Ribose-5-P + ADP +2H6 Ribose-5-P + ADP +2H++
GlycolysisGlycolysis
中間代謝物中間代謝物
當當 NADPHNADPH 需要量需要量 = Ribose-5-P= Ribose-5-P 需要量需要量
6 G-6-P + 2 NADP6 G-6-P + 2 NADP++
+ H+ H22OO 5 Ribose-5-P + 2 NADPH+5 Ribose-5-P + 2 NADPH+
2 H2 H++
+ CO+ CO22
Ribulose-5-PRibulose-5-P 完全氧化產生完全氧化產生 NADPHNADPH 進行糖質新生進行糖質新生
6 G-6-P + 12 NADP6 G-6-P + 12 NADP++
+7 H+7 H22OO 6 CO6 CO22 ++
12 NADPH + Pi+ 12 H12 NADPH + Pi+ 12 H++
當當 NADPHNADPH 需要量需要量 = ATP= ATP 需要量需要量
3 G-6-P + 6 NADP3 G-6-P + 6 NADP++
+ 5 NAD+ 5 NAD++
+ 5 Pi +8 ATP+ 5 Pi +8 ATP  55
pyruvatepyruvate ++ 6 NADPH + 5 NADH + 8 ATP6 NADPH + 5 NADH + 8 ATP + 8 H+ 8 H22O + 8 HO + 8 H++
體內重要的抗氧化酵素需要體內重要的抗氧化酵素需要 NADPHNADPH 還原成還原態還原成還原態
2 GSH + ROOH2 GSH + ROOH  GSSG + ROH + HGSSG + ROH + H22OO
Glutathione peroxidaseGlutathione peroxidase
Flavoprotein Glutathione reductaseFlavoprotein Glutathione reductase
(( 需要需要 NADPHNADPH 使使 –– S-S-S-S- 還原成還原成 -SH)-SH)
缺乏缺乏 G-6-P dehydrogenaseG-6-P dehydrogenase 導致溶血性貧血導致溶血性貧血
Biochemistry
Sixth Edition
Chapter 21:
Glycogen Metabolism
Berg • Tymoczko • Stryer
身體需要的能量時,迅
速轉換成 glucose ,並
產生能量
Glycogen 的功
用在維持血糖的
恒定
Structure of Glycogen
直鏈— α-1,4 linkage
支鏈— α-1,6 linkage
非還原端
肝細胞中細胞質電子顯微鏡圖
肝糖的三個代謝路徑肝糖的三個代謝路徑
需要能量時
提供組織利用,
維持血糖恆定
DNA 、 RNA
、 β-
oxidation 等
Glycogen phosphorylase—Glycogen phosphorylase—
剪切後以磷酸根取代剪切後以磷酸根取代 1st1st 碳的殘基,碳的殘基,
切下一個切下一個 glucoseglucose 分子。分子。
由非環原端逐次
切下 glucose 分
子,切下的
glucose 轉換成
G-1-P 。
支鏈的殘基轉移至
直鏈部分
切除支鏈的剩下的
一個殘基完全直鏈狀
態
G-6-P
(Debranching enzyme)(Debranching enzyme)
去分支水解酵素去分支水解酵素
物是產物是產 glucoseglucose ,不是,不是 G-1-PG-1-P
αα-1,6 glucosidase-1,6 glucosidase
Epimer ( 表異構物 ) : Gal Glc
G-6-P
Glycolysis
pathway
Phosphoglucomuta
se
Gal-1-P
G-1-P
轉移帶有磷酸根的 uridine 到
Gal-1-P 原本的 UDP-glucose 轉變成
G-1-P
與醣類代謝路徑接軌
的酵素
PhosphoglucomutasePhosphoglucomutase
與醣類代謝路徑接軌的酵素
G-6-P
Glucose
Glycolysis
糖質新生,維持血糖恆定
糖解代謝,產生能量
Pentose
phosphate
pathway
PhosphoglucomutasePhosphoglucomutase
G-6-PhosphaseG-6-Phosphase
只有只有 LiverLiver 才具有的酵素才具有的酵素
內質網內質網
Glucose
主要提供腦細胞與主要提供腦細胞與
骨骼肌利用骨骼肌利用
Glycogen phosphorylase
HomodimerHomodimer
同分子量同分子量
可與磷酸鹽受可與磷酸鹽受
質結合的部位質結合的部位
Glycogen
phosphorylase
所需要的輔酶
Pyridoxine (Vit
B6) 的衍生物
GlucoseGlucose G-1-PG-1-P
Glycogen
phosphorylase
作用機制
Glycogen
phosphorylase
的活性調控
Insulin
胰島素 Epinephri
ne
腎上腺素
Glucagon
昇糖激素
Regulation Glycogen MetabolismRegulation Glycogen Metabolism
Muscle Liver
Glycogen
phosphorylase
的活性調控
產生能量供 Muscle 利用 維持全身組織
glucose 的恒定
Muscle Glycogen Phosphorylase
Phosphorylase a
Relaxed state
不受 AMP 、 ATP 與
G-6-P 影響,一直具有活性
Phosphorylase b
常以 Tense state
High AMP conc. 時有活性 R stat
High ATP conc. 低活性 T state
High G-6-P 抑制活性  T stateEpinephrine ↑
興奮、恐懼、運動
Phosphorylase kinase
平衡時以平衡時以
Tense stateTense state
存在,不具有活存在,不具有活
性。性。
AMP↑AMP↑ ATP↑ATP↑
Phosphorylase
kinase
Phosphorylase
kinase
具有活性
具有活性
Epinephrine ↑
興奮、恐懼、運動
G-6-P↑G-6-P↑
缺乏能量時
能量充足時
不具有活不具有活
性性
具有活性具有活性
LiverLiver 中 Phosphorylase 的調
控方式— 當血糖濃度低時活性增加。
不具有活不具有活
性性
具有活性具有活性
GlucoseGlucose 充充
足,足, GlycogenGlycogen 沒有沒有
必要分解產生必要分解產生
glucoseglucose
不受不受 AMPAMP 影響,影響,
因為因為 liverliver 中不如中不如
肌肉中會有劇烈的能肌肉中會有劇烈的能
增加 Ca2+
含量
磷酸化
β-subunit 被磷酸化
δ-subunit 被鈣離子化
得到最大活性
Phosphorylase kinase
Epinephrine 與 Glucagon
對於肝醣代謝之調控
胰臟
腎髓質
ReceptorReceptor
ReceptorReceptor
1. Epinephrine 與 Glucagon
進入 transmenbrane 與特定
receptor 結合 。
2. 結合後活化 Gs protein ,然
後活化 G-protein 。
3. GTP Gs subunit 活 化
adenylate cyclase 。
1. Epinephrine 與 Glucagon
進入 transmenbrane 與特定
receptor 結合 。
2. 結合後活化 Gs protein ,然
後活化 G-protein 。
3. GTP Gs subunit 活 化
adenylate cyclase 。
GTPase
終止肝醣分解
Regulatory Cascade for Glycogen Breakdown.
1.Glycogen degradation is stimulated by hormone
binding to 7TM receptors.
2.Hormone binding initiates a G-protein-dependentG-protein-dependent
signal-transduction pathwaysignal-transduction pathway
3.that results in the phosphorylation and activationactivation
of glycogen phosphorylase.of glycogen phosphorylase.
Glycogen synthesis
(Uridine triphosphate)
(UDP-Glucose
pyrophosphoryla
se)
UDP-glucose, the glucose donor in the biosynthesis of glycogenglucose donor in the biosynthesis of glycogen, is an
activated form of glucoseactivated form of glucose, just as ATP and acetyl CoA are activated forms
of orthophosphate and acetate, respectively.
hydroxyl group is esterified to thehydroxyl group is esterified to the
diphosphate moiety of UDP.diphosphate moiety of UDP.
Glycogen
synthase
Glycogen 合成的關鍵酵素—
只能作用在超過 4 個殘基的多醣鏈
上
Glycogenin ( 肝醣合成蛋白 )
分支 α-1,6 由 branching
enzyme 轉移合成
A Branching Enzyme Forms α-1,6
Linkages
Branching is important because it increases
the solubility of glycogen.
Furthermore, branching creates a large number
of terminal residues, the sites of action of
glycogen phosphorylase and synthase
Thus, branching increases thebranching increases the rate of glycogen
synthesis and degradation.
 Glycogen branching requires a
single transferase activity.
 Glycogen debranching requires
two enzyme activities: a transferase and
an α -1,6 glucosidase.
Synthase a
不受 G-6-P 影響
,一直具有活性
Synthase b
不具活性
Glycogen
sythatase kinase
/
Protein kinase A
High G-6-P
concentration
合成肝醣
G-6-P  G-1-P
UTP
UDP-glucose
PPi
H2O
Pi
Glycogen (n)
Glycogen (n+1)
UDP
ATP
ADP
Glycogen synthesis pathway
抑制肝醣合成
運動時需要肝醣分解以提高
血糖濃度與能量
bbaa
具有活性不具活性
PP1
使 GM 磷酸
化 與 PP1
分離
肌肉中肝醣結合
位置
肌肉中的小分子
protein
運動過程中,使 Protein Phosphotase 1
(PP1) 失去活性以抑制肝醣生成之作用機
制
Insulin 對於 Glycogen
synthesis 的調控—
Glycogen synthase
kinase
(Insulin receptor substrate)(Insulin receptor substrate)
Insulin 活化 Glycogen
sythase kinase 活性以
促進 Glycogen
synthesis
作用在使作用在使 GlycogenGlycogen
synthesissynthesis 維持在不維持在不
活化的狀態活化的狀態
不活化狀態不活化狀態
活化狀態活化狀態
活化狀態活化狀態 不活化狀態不活化狀態
Wk11 glycogen metabolism
Wk11 glycogen metabolism

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Wk11 glycogen metabolism