Biochemistry: Metabolism

(from 100 to 112-1)

王琬菁
生化暨分子生物研究所
傳醫乙棟 R606
wangwj@nycu.edu.tw ; (02)2826-7117
 Metabolism Overview
 Two main processes in metabolism:
分解代谢 合成代谢
catabolism and anabolism.

(1) Catabolism: The breakdown of

large molecules into smaller units.
Energy is released (generate ATP,
NADH, NADPH, or FADH2).
(2) Anabolism: Energy is used to
build larger molecules from small
units (require NADPH).

Chemical energy
• ATP: energy currency.
• NADH, NADPH, or FADH2: (Coenzymes, derived from
adenine)
Pass Test Questions
(A) 29. Coenzyme A ， NAD+ ，和 FAD 都利用下列何種物質作為它們的共
同成分？
A. Adenine
B. Guanine
C. Cytosine
D. Thymidine

(B) 30. 下列何者主要是負責細胞還原生合成（ reductive biosynthesis ）反

應之輔酶？
A. NADH
B. NADPH
C. FADH2
D. FMNH2
Carbohydrate Metabolism
肝糖
 Glycolysis
 From 1 Glucose (C6) to 2 pyruvate (C3).
 Two phases:
(1) Energy-investing phase: require 2ATP
(2) Energy-generating phase: generates 4ATP and 2NADH

Step 1-5

Step 6-10
 Energy-investing phase
Glucose

 Activation by
phosphorylation: It
requires 2 ATP.
(Hexokinase and
phosphofructokinase). Glucose-6-phosphate (G6P)

 One glucose is cleaved to

form 2 GAP Fructose-6-phosphate (F6P)

(glyceraldehyde-3- Fructose-1,6-bisphosphate (FBP)

phosphate, GAP, G3P)(by
aldolase).

Glyceraldehyde-3-phosphate
(GAP, G3P)

Dihydroxyacetone
phosphate (DHAP)
 Energy-generating phase
 GAP is converted
1,3-Bisphosphoglycerate
to pyruvate. (BPG)

GAP Pyruvate

3-Phosphoglycerate (3PG)

 4 ATP and 2 NADH

are produced.
Phosphoenolpyruvate (PEP)
 Regulation of Glycolysis

Step 1
-High levels of
glucose-6-phosphate

Step 3

-Fatty acid
synthesis is active

Step 10
Pass Test Questions
(D) 87. 將一莫耳 (mole) 葡萄糖經由糖解作用 (glycolysis) 產生兩莫耳丙酮酸
(pyruvate) 的過程中，淨需要：
A. 四莫耳 ATP
B. 一莫耳 NAD+
C. 一莫耳磷酸根 (inogrganic phosphate)
D. 兩莫耳 ADP

(B) 40. 有一種罕見糖尿病，是由於 hexokinase 之基因突變所造成，其

substrate 是：
A. fructose
B. glucose
C. galactose
D. sucrose
(B) 40. 在糖解（ glycolysis ）作用中，那個酵素的功能可將六碳糖分解為兩個
三碳糖？
A. phosphohexose isomerase
B. aldolase
C. triose phosphate isomerase
D. enolase
Pass Test Questions
(D) 39. 下列那一個代謝途徑不會產生二氧化碳？
A. 五碳糖磷酸途徑（ pentose phosphate pathway ）
B. 克氏循環（ TCA cycle ）
C. 從草醯乙酸（ oxaloacetate ）開始的糖質新生作用
（ gluconeogenesis ）
D. 糖解作用（ glycolysis ）
(B) 95. 葡萄糖進入細胞後，主要經由下列何種修飾將其留在細胞內進行代謝？
A. glycosylation
B. phosphorylation
C. palmitoylation
D. acetylation

(D) 90. 葡萄糖在細胞內代謝成 acetyl-CoA 的過程中，不需要下列何者參與？

A.glyceraldehyde 3-phosphate dehydrogenase
B.pyruvate kinase
C.pyruvate dehydrogenase complex
D.phosphoenolpyruvate （ PEP ） carboxykinase
Pass Test Questions
(B) 88. 下列那一個酵素所催化的反應為糖解作用（ glycolysis ）中唯一將電子轉
移給 NAD+ 之氧化還原反應？
A. enolase
B. glyceraldehyde-3-phosphate dehydrogenase
C. pyruvate dehydrogenase
D. pyruvate kinase
 Polysaccharide/Glycogen degradation

 In animal metabolism, two primary

sources of glucose are derived from
polysaccharides:
1
1. Mobilization of the animal’s own
glycogen reserves. Glycosidic
bond
2. Digestion of dietary
polysaccharides, chiefly starch
from plant foodstuffs and 2
glycogen from meat.
 Cleavage of a glycosidic bond by
(1) hydrolysis or (2) phosphorolysis.
 Glycogen Metabolism

 Glycogen is the form of stored glucose.

 Glycogen is stored primarily in the liver and skeletal muscle.
 The function of muscle glycogen is to serve as a fuel
reserve.
 The function of liver glycogen is to maintain blood glucose
level.
 Glycogen synthesis
 Glycogen is a multibranched polysaccharide
of glucose. 由葡萄糖脫水缩合作用而成

 Three enzymatic steps

are required to
incorporate one G6P into
glycogen

 UDP-glucose is the
metabolically activated
form of glucose for
glycogen synthesis.
 Glycogen breakdown in muscle and liver
 Glycogen degradation involves sequential phosphorolytic
cleavages of Glycosidic bonds, catalyzed by glycogen
phosphorylase.

Glucose-1-P

Phosphoglucomutase ( 葡萄糖磷酸變位酶 )

Glucose-6-P
 Catabolism of sugars other than glucose
 In animals, most of the carbohydrate other than glucose
(Glycogen) comes from the diet.

乳糖

麥芽糖

甘露糖

蔗糖
 Lactose and galactose to glucose (Leloir pathway)
 Leloir pathway: For utilizing lactose and galactose by converting it to
glucose-6-phosphate
 Galactose-1-phosphate undergoes an exchange reaction with UDP-
glucose, which is catalyzed by galactose-1-phosphate uridyltransferase
and releases glucose-1-phosphate and UDP-galactose.
 Enzyme defects cause galactosemia 半乳糖血症

半乳糖

乳糖
Pass Test Questions
(D) 39. UDP-glucose 參與下列那個代謝路徑？
A. 五碳糖磷酸途徑（ pentose phosphate pathway ）
B. 肝醣分解（ glycogen degradation ）
C. 糖解作用（ glycolysis ）
D. 半乳糖轉變為葡萄糖（ epimerization of galactose to glucose ）

(B) 37. 下列何種情況，導致遺傳疾病半乳糖血症（ galactosemia ）的發生？

A. 缺少 fructokinase
B. 缺少 UDP-glucose:galactose 1-phosphate uridylyltransferase
C. 無法分解 lactose
D. 過度攝取 galactose
(C) 94. 雙醣分子（ disaccharide ）為兩個單醣分子（ monosaccharide ）依
照特定的方式組合，經縮合反應除去一個水分子而形成。下列何者為麥芽糖
（ maltose ）？
A.Glcα(1→2)Fru
B.Galβ(1→4)Glc
C.Glcα(1→4)Glc
D.Glcα(1→1)Glc
Pass Test Questions
(A) 64. 下列何種酵素可幫助麥芽糖（ maltose ）水解成為葡萄糖？
A. 蔗糖酶（ sucrase ）
B. 乳糖酶（ lactase ）
C. 海藻糖酶（ trehalase ）
D. 澱粉酶（ amylase ）
 Gluconeogenesis
Synthesis and use of glucose in
the human body  Liver and kidney cortex are the
primary gluconeogenic tissues.
 Brain, skeletal muscle, kidney
medulla, erythrocytes, and
testes use glucose as their sole
or primary energy source, but
they lack the enzymatic
machinery to synthesize it.
 Synthesis of glucose from
noncarbohydrate precursors is
essential for maintenance of
blood glucose levels within
acceptable limits.
 Glycolysis and gluconeogenesis
 Gluconeogenesis uses specific enzymes to bypass three
irreversible reactions of glycolysis (Step 1, 3, and 10).

Step 1

Step 3

Step 10
 Gluconeogenesis: Bypass 1
Bypass 1: Conversion of Pyruvate to Phosphoenolpyruvate
(PEP)
 The bypass of pyruvate kinase begins in the mitochondria and
involves two reactions.
 Gluconeogenesis: Bypass 1
 Reaction 1: Pyruvate carboxylase catalyzes the CO2, ATP,
and biotin-dependent conversion of pyruvate to oxaloacetate.
biotin

 Reaction 2: OAA is catalyized by phosphoenolpyruvate

carboxykinase (PEPCK) to give phosphoenolpyruvate (PEP).
GTP is used as a phosphorylating agent
 Gluconeogenesis: Bypass 2 and 3
 Two bypass reactions in gluconeogenesis involves simple
hydrolytic reactions that catalyzed by fructose-1,6-
bisphosphatase and glucose-6-phosphatase.
Glycolysis and gluconeogenesis
Precursors for gluconeogenic
 The important gluconeogenic precursors:
 Coordinated Regulation of Glycolysis and
Gluconeogenesis
 Fructose-2,6-bisphosphate is the most important regulator of
glycolysis and gluconeogenesis. 共同異位調解因子 (allosteric
regulator)

 Fructose-2,6-bisphosphate is synthesized and degraded by a

bifunctional enzyme (PFK-2/FBPase-2).
Insulin and glucose
Inhibit glycolysis Activate glycolysis

Glucagon 昇糖激素
Regulation of Glycolysis and Gluconeogenesis

+ F2, 6BP
 Pass Test Questions
(A) 38. 下列何種物質無法作為葡萄糖生合成（ gluconeogenesis ）之前驅物？
A. 脂肪酸
B. 胺基酸 arsenate
C. 甘油（ glycerol ）
D. 草醯乙酸（ oxaloacetate ）

(C) 38. Fructose 2,6-bisphosphate 是糖解作用（ glycolysis ）與糖質新生作用

（ gluconeogenesis ）的重要共同異位調解因子（ allosteric regulator ），下列
有關 fructose 2,6-bisphosphate 的敘述何者正確？
A. 昇糖激素（ glucagon ）促進其合成
B. fructose 2,6-bisphosphatase 催化其由 fructose 6-phosphate 合成
C. fructose 2,6-bisphosphate 活化 phosphofructokinase-1
D. fructose 2,6-bisphosphate 增加糖質新生作用（ gluconeogenesis ）

(D) 88. 病人無法進食時 , 因為肝臟可以進行 gluconeogenesis, 一般仍不至於發

生低血糖 , 下列何種物質無法被轉化為 glucose ？
A. lactate
B. alanine
C. glycerol
D. ethanol
Pass Test Questions
(A) 39. 下列有關人體細胞進行葡萄糖新生作用（ gluconeogenesis ）之敍述何
者正確？
A. 可將蛋白質轉變成血糖
B. 胰島素可活化葡萄糖新生作用
C. 攝取高醣類食物後，利用此作用來降低血糖
D. 脂肪酸轉變成葡萄糖之必需途徑

(B) 36. 下列那一個分子不是糖解作用（ glycolysis ）與糖質新生

（ gluconeogenesis ）共同的中間產物？
A. 磷酸烯醇式丙酮酸（ phosphoenolpyruvate ）
B. 草醯乙酸（ oxaloacetate ）
C. 1,3- 二磷酸甘油酸（ 1,3-bisphosphoglycerate ）
D. 6- 磷酸葡萄糖（ glucose 6-phosphate ）

(D) 87. 下列那種酶在肌細胞中含量較低 , 無法有效進行糖合成作用

(gluconeogenesis) ？
A. 丙酮酸脫氫酶（ pyruvate dehydrogenase ）
B. 磷酸果糖磷激酶 -1 （ phosphofructokinase-1 ）
C. 肝醣合成酶（ glycogen synthase ）
D. 葡萄糖 6- 磷酸酶（ glucose 6-phosphatase ）
Pass Test Questions
(A) 38. 下列那種酶同時參與糖解（ glycolysis ）及葡萄糖新生
（ gluconeogenesis ）之代謝途徑？
A. 3- 磷酸甘油酸激酶（ 3-phosphoglycerate kinase ）
B. 六碳糖激酶（ hexokinase ）
C. 磷酸果糖激酶 -1 （ phosphofructokinase-1 ）
D. 丙酮酸激酶（ pyruvate kinase ）

(C) 36. 常見的 glycogen storage disease 是因為病人缺乏 glucose-6-

phosphatase 所造成，下列敘述何者正確？
A. glycogen synthesis 增加
B. glucose-6-phosphate 無法轉化成 glucose-1-phosphate
C. 病人血中 glucose 濃度可能偏低
D. glycolysis 異常

(C) 90. 細胞進行糖質新生（ gluconeogenesis ）時，需要下列那兩種酵素共同

作用將 pyruvate 轉換為 phosphoenolpyruvate ？
A. pyruvate kinase and pyruvate dehydrogenase
B. pyruvate carboxylase and pyruvate kinase
C. pyruvate carboxylase and phosphoenolpyruvate carboxykinase
D.pyruvate dehydrogenease and phosphoenolpyruvate carboxykinase
 Pentose Phosphate Pathway(PPP)

 It converts glucose to various other sugars, while produce

energy (NADPH) at the same time.

 Two phases of pentose phosphate pathway

(1) Oxidative
phase…………………………………....irreversible reactions

(2) Nonoxidative (interconversion) phase ………..reversible

reactions
 Oxidative phase of PPP
 Glucose 6-phosphate dehydrogenase (G6PD) is the key
enzyme of the pathway. 缺陷造成蠶豆症
 The pathway is inhibited by NADPH and activated by NADP+
 In the oxidative phase, glucose-6-phosphate is oxidized to
ribulose-5-phosphate and CO2, with production of 2NADPH.
 Nonoxidative reaction of PPP pathway

Ribose-5-P

Fructose-6-P

G3P

Net reaction:
The importance of pentose phosphate pathway
 Energy generation: It
generates NADPH.

 Nucleotide synthesis: It
generates Ribose-5-
phosphate for nucleotide
biosynthesis.

 Glycolysis: The pentoses

are converted to
Fructose-6-phosphate
and glyceraldehyde-3-P
that are intermediates of
glycolysis.
Pass Test Questions
(D) 80. 下列關於戊糖磷酸途徑（ pentose phosphate pathway ）的敘述，何
者錯誤？
A. 產生 NADPH 供還原反應使用
B. 產物可轉換成 ribose-5-phosphate 供核苷酸合成使用
C. 反應中 glucose-6-phosphate dehydrogenase 缺乏會導致蠶豆症
的發生
D. 該反應速率限制酵素 (rate limiting enzyme) 為 6-phospho-
gluco-lactonase
(Glucose 6-phosphate dehydrogenase)
(B) 28. 下列何種化合物不是五碳糖途徑（ pentose phosphate pathway ）
之代謝物或產物？
A. NADPH
B. α-ketoglutarate
C. CO2
D. Ribulose 5-phosphate
(C) 87. 下列有關葡萄糖氧化的五碳糖磷酸途徑（ pentose phosphate
pathway ）功能之敘述，何者正確？
A. 負責催化每莫耳葡萄糖產生 36 莫耳 ATP
B. 負責催化每莫耳葡萄糖產生 5 莫耳 CO2
C. 供應合成核苷酸（ nucleotide ）所需要之核糖（ ribose ）的來源
D. 主要功能是產生 NADH 及 FADH2 進入呼吸鏈氧化產生能量
 Pyruvate metabolism
 Pyruvate represents a central metabolic branch point.
 The fate of pyruvate
depends crucially on
the oxidation state
(ratio of
NAD+/NADH).

Lactate
dehydrogenase

Cytosol
Cytosol
Mitochondria
 Lactate pathway and ethanol pathway
 Pyruvate to lactate: When tissues are insufficiently aerobic
to oxidize all of the NADH formed in glycolysis.

Lactate
dehydrogenase

Acetyl-CoA
Human
 Pyruvate oxidation and respiration

1. Pyruvate oxidation
Pyruvate converts to acetyl-CoA

2. The citric acid cycle

Acetyl-CoA is oxidized to
produce CO2, reduced electron
carriers (NADH and FADH2),
and a small amount of ATP.

3. Electron transport
4. Oxidative phosphorylation
The reduced electron carriers
are reoxidized for ATP
synthesis.
 Pyruvate oxidation
 If the oxygen is present, pyruvate molecules are transported
from cytosol to mitochondria matrix to form acetyl-CoA.
 Pyruvate oxidation is catalyzed by pyruvate dehydrogenase
complex (PDH complex)
 It involves three enzymes and five coenzymes.
 Pyruvate Dehydrogenase Complex
Three enzymes:
E1: pyruvate dehydrogenase: It removes CO2

E2: dihydrolipoamiide transferase: transfers the substrate to coenzyme A

E3: dihydrolipoamide dehydrogenase: transfers the H 2 that was retained in

the preceding steps to NAD+.
Structure of the pyruvate
dehydrogenase complex

Five coenzymes:
Pass Test Questions
(B) 87. 在動物細胞內，下列何者為葡萄糖進行無氧糖解（ anaerobic
glycolysis ）之淨產物？
A. ATP 和 pyruvate
B. ATP 和 lactate
C. NAD+ 和 ethanol
D. ATP 和 acetyl-CoA

(B) 40. 百米選手在激烈運動下，骨骼肌內之糖解作用（ glycolysis ）所產生的

NADH ，最主要經由下列何種反應再氧化生成 NAD+ ？
A. α-ketoglutarate 反應成為 succinyl-CoA
B. pyruvate 反應成為 lactate
C. coenzyme Q 反應成為 cytochrome b
D. pyruvate 反應成為 acetyl-CoA

(B) 40. 紅血球因缺乏粒線體，其葡萄糖分解的最終產物為何？

A. pyruvate
B. lactate
C. acetyl-CoA
D. CO2
Pass Test Questions
(B) 36. 抑制細胞內乳酸去氫酶（ lactate dehydrogenase ）的活性會影響下列
那些反應的進行？
A. 克氏循環（ TCA cycle ）無法進行
B. 無氧狀態的糖解作用（ anaerobic glycolysis ）無法進行，克氏循環
（ TCA cycle ）不受影響
C. 無氧狀態的糖解作用（ anaerobic glycolysis ）與克氏循環（ TCA
cycle ）皆無法進行
D. 氧化磷酸化作用（ oxidative phosphorylation ）與克氏循環（ TCA
cycle ）皆無法進行

(C) 95. 一新生兒發生非常嚴重乳酸中毒 (lactic acidosis), 進一步檢查發現有丙

酮酸脫氫酵素 (pyruvate dehydrogenase) 缺乏 , 下列敘述何者正確？
A. 在有氧狀況下，丙酮酸轉化為乳酸（ lactic acid ）及乙醇
（ ethanol ）
B. 在無氧狀況下，丙酮酸在粒線體轉化為乙醯輔酶 A （ acetyl-CoA ）
C. 丙酮酸脫氫酵素是由三種酵素複合體結合而成
D. 神經系統不會受到影響
Pass Test Questions
(D) 87.Pyruvate dehydrogenase （ PDH ）為催化 pyruvate 轉化為 acetyl-CoA
進入克氏循環（ Krebs cycle 或稱 TCA cycle ）的重要酵素。下列何者不是
PDH 會用到的 co-factor ？
A.flavin adenine dinucleotide （ FAD ）
B.Lipoamide
C.thiamine pyrophosphate （ TPP ）
D.pyridoxal phosphate （ PLP ）
(B) 89. 經由糖解作用（ glycolysis ）產生的丙酮酸（ pyruvate ）必須直接先被
轉換為下列何種分子，才能繼續以克式循環（ Krebs cycle ，亦稱 citric acid
cycle 或 TCA cycle ）進行氧化？
A.lactic acid
B.acetyl-CoA
C.S-adenosylmethionine
D.phosphoenolpyruvate
(C) 93. 下列糖解作用（ glycolysis ）的步驟中，那一個酵素所催化的步驟在正
常生理條件下為不可逆反應？
A. enolase
B. phosphoglycerate kinase
C. pyruvate kinase
D. aldolase
The Citric Acid Cycle (TCA cycle, Kerbs Cycle)
 It occurs in the mitochondria matrix over 8 different steps.
 1 TCA cycle generates:
- 1 (ATP or GTP)
- 3 NADH
- 1 FADH2
- 2 CO2

 It requires cofactor
CoA-SH
 Regulation of TCA Cycle

 In the complete
degradation of
pyruvate, pyruvate,
pyruvate is converted
to CO2.
 Isocitrate
dehydrogenase at
step 3 of the TCA C6
cycle: The rate
Step 3
limiting step of the
cycle. C5

C4
The link between TCA cycle intermediates
and other metabolic pathway
Pass Test Questions
(A) 88. 下列關於克式循環（ Krebs cycle ，亦稱 citric acid cycle 或 TCA
cycle ）的敘述，何者正確？
A. 在克式循環過程中， oxaloacetate 淨消耗 (net consumption) 為零
B. 在克式循環過程中，不涉及受質階層磷酸化（ substrate-level
phosphorylation ）
C. 一次的克式循環會產生一個分子的二氧化碳
D. 一次的克式循環會產生四個分子的 FADH2
(C) 38. 下列何種分子不會直接參與克式循環（ Krebs cycle ，亦稱 citric acid
cycle 或 TCA cycle ）中的化學反應？
A. coenzyme A （ CoA ）
B. ADP （或 GDP ）
C. glutathione
D. NAD+
(B) 29. 下列何種輔酶（ coenzyme ）不參與 α-ketoglutarate 轉換成 succinyl-
CoA 之氧化脫羧反應（ oxidative decarboxylation ）？
A.Thiamine pyrophosphate
B.Tetrahydrofolate
C.FAD
D.Coenzyme A
(C) 38. 克氏循環（ TCA cycle ）中那種酵素的受質為一個四碳化合物？
A. 異檸檬酸脫氫酶（ isocitrate dehydrogenase ）
B. 烏頭酸酶（ aconitase ）
C. 檸檬酸合成酶（ citrate synthase ）
D. 乳酸脫氫酶（ lactate dehydrogenase ）
(A) 95. 下列那一種克式循環（ Krebs cycle ，亦稱 citric acid cycle 或 TCA
cycle ）的中間產物可以不經由 NADH 的產生，而將其電子直接傳遞給電子
傳遞鏈中的複合體 II （ complex II ）進行氧化？
A. succinate
B.citrate
C.α-ketoglutarate
D.malate
 Electron Transport Chain (ETC)
 Four complexes (I-IV)
together with associated
electron carriers
(ubiquinone and
cytochrome C) is called
the ETC.
 They are embedded in the
inner mitochondrial
membrane that shuttle
electrons carried by
NADH and FADH2.

 These complexes actively

pump protons outward,
creating an energy
gradient for ATP
synthesis (complex V).
 The composition of electron transport chain
 Complex I: NADH dehydrogenase Iron–sulfur clusters
complex, 催化電子由 NADH 傳到 Cysteine
ubiquinone (Coenzyme Q).
 Complex II: Succinate dehydrogenase
與硫鐵蛋白 (2Fe-2S center; Iron–sulfur
clusters) 組成，催化電子由 FADH2 傳至
ubiquinone 。
 Complex III: 由 2 個 B-type cytochrome 、
cytochrome C1 與硫鐵分子 (2Fe-2S Cytochrome c and c1
center;) 組成，將 ubiquinone 攜帶的電子傳 Cysteine
遞至 cytochrome C
 Complex IV: 由 cytochrome oxidase 組
成，催化 4 個電子與 O2 形成 H2O 。

 Two electron carriers (ubiquinone and

cytochrome C): Shuttle electrons.
 Chemiosmotic coupling of electron transport and
ATP synthesis
 Protons are pumped as electrons flow through the complexes
that generate electrochemical gradient across membrane.
 Proton re-entry to the matrix, through the F0 channel of ATP
synthase (complex V), provides the energy to drive ATP
synthesis.
 Inhibitors for Electron Transport Chain
 Retenone and amytal inhibit NADH dehydrogenase
(complex I) 。
 CO ， azide(N3-) and cyanide(CN-) inhibit cytochrome
oxidase 。
 Antimycin A inhibit cytchrome b 。
Pass Test Questions
(C) 46. 下列那一個酵素位於粒線體電子傳遞鏈的 Complex II ？
A. NADH dehydrogenase
B. cytochrome c oxidase
C. succinate dehydrogenase
D. ubiquinol-cytochrome c oxidoreductase

(C) 47. 粒線體電子傳遞鏈的 Complex Ⅳ 主要是把電子由那裏傳遞到 O2 ？

A. Ubiquinone
B. NADH
C. Cytochrome c
D. Succinate

(A) 48. 粒線體進行電子傳遞過程中容易產生下列何種對細胞有害的物質？

A. reactive oxygen species(ROS)
B. CO
C. NH3
D. O2
Pass Test Questions
(A) 49. 粒線體電子傳遞鏈的 Complex III 主要是把電子傳遞到 :
A. Cytochrome c
B. Succinate
C. NADH
D. Ubiquinone

(D) 45. 參與電子傳遞鏈的蛋白質複合體使用那一種胺基酸形成 iron-sulfur

center ，輔助電子傳遞？
A. 丙胺酸（ alanine ）
B. 甲硫胺酸（ methionine ）
C. 色胺酸（ tryptophan ）
D. 半胱胺酸（ cysteine ）

(A) 46. 下列何者為粒線體電子傳遞鏈 Complex I 的 electron donor ？

A. NADH
B. Cytochrome c
C. Coenzyme Q
D. Succinate
 Pass Test Questions
(C) 44. 一氧化碳（ CO ）是粒線體的電子傳遞鏈抑制劑，其主要作用機制是下
列何者？
A. 抑制 ATP synthase
B. 抑制 cytochrome b 到 cytochrome c1 之電子傳遞
C. 抑制 cytochrome oxidase
D. 抑制電子由 Fe-S 中心流至 ubiquinone

(B) 46. 粒線體氧化磷酸化之去偶合（ uncoupling ）會造成下列何種現象？

A. ATP 持續合成，但停止 O2 消耗
B. ATP 不合成，但 O2 仍然消耗
C. 抑制粒線體之所有代謝反應
D. 抑制電子傳遞及 O2 之消耗

(C) 96. 下列關於電⼦傳遞鏈的敘述，何者錯誤？

A. 氧分⼦（ O2 ）為電⼦最終的接受者
B. NADH 的氧化發⽣於 complex I
C. Coenzyme Q （ CoQ ）可協助將電⼦由 complex I 傳遞⾄ complex II
D. Cytochrome c （ Cyt c ）可協助將電⼦由 complex III 傳遞⾄
complex IV
Pass Test Questions
(A) 49. Rotenone 會抑制粒線體電子傳遞鏈的那一個步驟？
A. NADH→coenzyme Q
B. Cyt b→Cyt c1
C. Cyt c1→Cyt c
D. Cyt c→Cyt (a+a3)

(A) 47. 下列那一種酵素參與克式循環（ Krebs cycle ，亦稱 citric acid cycle 或

TCA cycle ）的反應，是位於粒線體內膜上且直接參與電子傳遞鏈？
A. succinate dehydrogenase
B. isocitrate dehydrogenase
C. alpha-ketoglutarate dehydrogenase complex
D. malate dehydrogenase

(D) 95. 在粒線體中， NADH 經由電子傳遞鏈（ electron transport chain ）進行

氧化時，氫離子（ H+ ）如何移轉？
A. 由粒線體內外膜間的間隙運送至細胞質
B. 由細胞質運送至粒線體內外膜間的間隙
C. 由粒線體內外膜間的間隙運送至粒線體基質（ matrix ）
D. 由粒線體基質（ matrix ）運送至粒線體內外膜間的間隙
Pass Test Questions
(C) 95. 參與電子傳遞鏈（ electron transport chain ）有四種蛋白質複合體，下
列那一組複合體均具有氫離子幫浦（ proton pump ）的活性？
A. complexes I, II, III
B. complexes I, II, IV
C. complexes I, III, IV
D. complexes II, III, IV

(C) 88. 下列有關克氏循環（ Krebs cycle 或稱 TCA cycle ）的步驟中，那一個酵

素所催化的步驟在正常生理條件下為不可逆反應？
A. aconitase
B. fumarase
C. citrate synthase
D. succinyl-CoA synthetase
(A) 96. 粒線體電子傳遞鏈的 Complex III 主要是把電子傳遞到：
A.cytochrome c
B.succinate
C.NADH
D.ubiquinone
Pass Test Questions
(C) 100. 粒線體的膜電位差對於 ATP synthase （ complex V ）所催化的 ATP 合
成是必需的，當一對電子從 NADH 藉由電子傳遞鏈轉移到氧分子（ O2 ）的過程
中，下列敘述何者正確？
A. Complex I 會將 4 個氫離子移轉到細胞質
B. Complex II 會將 2 個氫離子移轉到粒線體內外膜間隙（ intermembrane
space ）
C. Complex III 會將 4 個氫離子移轉到粒線體內外膜間隙（ intermembrane
space ）
D. Complex IV 會將 2 個氫離子移轉到粒線體基質（ matrix ）

(B) 96. 下列何者為粒線體電子傳遞鏈 complex IV 之電子供應者（ electron

donor ）？
A. succinate
B. cytochrome c
C.coenzyme Q
D.NADH
 Pass Test Questions
(B) 88. 下列有關克氏循環（ Krebs cycle ，或稱 TCA cycle ）的敘述，何者正確？

A. 克氏循環過程中沒有 substrate-level phosphorylation

B. 一次完整的克氏循環會產生兩分子的 CO2
C. 一次完整的克氏循環會產生兩分子的 NADH
D. 一次完整的克氏循環會產生兩分子的 FADH2

(A) 96. 某新物種中粒線體的 complex V ，其 F0 之 c-ring 由 12 個 c subunit 所

組成，而 F1 complex 中的 αβ dimer 共有 6 組。依據目前已知 complex V 作用
機轉，此物種的 complex V 每合成一個 ATP 最有可能需要幾個氫離子通過粒線
體內膜（ inner membrane ）？
A. 2
B. 3
C. 4
D. 6
Lipid metabolism
-Lipid, membrane, and cellular transport
 Nomenclature of fatty acids

(C) 43. 脂肪酸 cis-, cis-delta 9, delta 12-octadecadienoate 是指下列

何者？
A. oleate 18:1cr9
B. palmitoleate 16:1cr9
C. linoleate 18:2cr9,12
D. arachidonate 20:4cr5,8,11,14
Lipid: The major constituents of biological membranes
 Membrane lipids are amphipathic.

 Major classes of membrane lipids.

o Glycerophospholipids
o Sphingolipids
o Glycospingolipids
o Glycoglycerolipids Glycolipid
o Cholesterol: The less amphipathic lipid.
 Diffusion of lipids in bilayers
 The diffusion of lipids in bilayers include transverse
diffusion (flip-flop) and lateral diffusion

Very slow
 Translocases or
flippasese: enzymes that
facilitate transverse
diffusion of lipids in
biological membrane
Rapid
 The properties of the biological membranes
 Membrane fluidity
-A functioning biological membrane is not a rigid, frozen
structure.
 The membrane fluidity is depend on the temperature and lipid
composition, and the presence of cholesterol.

bilayer width Formation of cholesterol

increases plaques in the circulatory
(become thickness) system or lipid rafts)
Pass Test Questions
(A) 40. 所有生物細胞膜內的脂雙層具有下列何種共同特色？
A. 個別的油脂分子能在脂雙層的表面自由地側向擴散（ lateral diffusion ）
B. 個別的油脂分子能夠快速在脂雙層中的其中一層自由翻轉擴散（ flip-flop
diffusion ）至另外一層
C. 具有極性但不帶電荷之化合物容易經由擴散穿過脂雙層
D. 脂雙層利用鄰近磷脂分子之間的共價鍵而形成穩定結構

(C) 1. 關於細胞膜上的膽固醇（ cholesterol ）其結構及功能的敘述，下列何者正確？

A. 與細胞膜相較，胞器膜（ membrane of the organelle ）上的膽固醇含量較
多
B. 膽固醇帶極性的羥基（ polar hydroxyl group ）鑲嵌於細胞膜的雙脂層
（ lipid
bilayers ）夾層內部（ interior ）
C. 膽固醇可幫助調節細胞膜的膜流動性（ membrane fluidity ）
D. 膽固醇在細胞膜內外側的分布是對稱的（ symmetric ）

(B) 47. 就低溫下幫助維持細胞膜的流動性（ membrane fluidity ）而言，下列何種化

學物質最為重要？
A. 飽和脂肪酸
B. 膽固醇
C. 穿膜蛋白
 Three classes of membranes proteins
1. Transmembrane proteins– They penetrate and pass through
lipid bilayer.
2. Peripheral proteins- They are attached to the membrane by
weak bonds.
3. Lipid-anchored proteins- They are distinguished both by the
types of lipid anchor and their orientation.
 Characteristics of transmembrane proteins
 Transmembrane proteins contain high proportion of hydrophobic
amino acids that are embedded in the membrane.
 The transmembrane regions typically contain 20-25 amino acid
residues.

Bacteriorhodopsin
Seven helices
細菌視紫蛋白

a-helical

Hydrophobicity plot
 Amino acids of transmembrane protein in lipid-
water interface
 Transmembrane protein domains often contain interfacial
aromatic residues.
 It may play a role in the insertion and stability of membrane
helices.
 Trp and Tyr are often found situated at the lipid-water interface .
 Lipid-anchored membrane proteins
 Many proteins involved in signal
transduction are modified in this
way.

 Three types are most common

Acylation
(1) Prenylated proteins (Prenylation)
Farnesylate proteins (C15 isoprene
unit)
Geranylgeranylate proteins (C20
isoprene unit)

(2) Fatty acylated proteins Prenylation

(Acylation)
Myristoylated proteins (C14)
Palmitoylated proteins (C16)

(3) Glycosylphosphatidylinositol-
linked proteins (GPI-anchored
proteins).
 Glycosylphosphatidylinositol-linked proteins
(GPI-anchored proteins)

 The GPI-modified proteins are frequently localized in regions of

the membrane that are enriched in cholesterol and
sphingolipids (also call lipid raft or membrane raft)
Pass Test Questions
(D) 42. 厭水性分析圖（ hydropathy plot ）一般可用於：
A. 推算膜蛋白質的四級結構
B. 測定天然的蛋白質（ native protein ）的水含量
C. 推算膜蛋白質的實際分子量
D. 預測已知的蛋白質胺基酸序列是否含有穿膜區（ membrane-
spanning
segment ）

(B) 43. 下列何者不屬於穿膜蛋白 - 細菌視紫蛋白（ bacteriorhodopsin ）的特性？

A. 它是利用 7 個 α- 螺旋結構形成的通道穿過細胞膜
B. 它是利用單一的 β- 螺旋結構穿過細胞膜
C. 它是藉由穿膜結構與 retinal 分子結合
D. 它具有光驅動質子運輸（ light-driven proton transport ）的功能

(C) 41. 穿越細胞膜（ transmembrane ）的蛋白質中，色胺酸（ tryptophan ）

最常位於何處？
A. 細胞膜脂肪層內（ intra-lipid bilayer ）
B. 細胞質的水相中
C. 細胞膜脂肪層與細胞質水相之交接處
D. 緊鄰於甘胺酸（ glycine ）
Pass Test Questions
(C) 92. 膜蛋白質最常以共價鍵結合下列何種脂質（ lipid ），而附著在細胞膜外
層上？
A. 硬脂酸（ stearic acid ）
B. 神經鞘氨醇（ sphingosine ）
C. 糖基化磷脂醯肌醇（ glycosyl phosphatidylinositol; GPI ）
D. 磷脂醯肌醇（ phosphatidylinositol ）

(C) 40. 下列何種分子是屬於 glycerophospholipid 並參與細胞內訊息傳遞？

A. arachidonic acid
B. vitamin C
C. phosphatidylinositol
D. phosphatidylethanolamine

(D) 41. 有關細胞膜上之脂膜筏（ lipid raft ），下列敘述何者正確？

A. 有較低量膽固醇（ cholesterol ）
B. 有較低量鞘脂（ sphingolipid ）
C. 不含有燒杯狀膜小囊蛋白（ caveolin ）
D. 有較高量的糖基化磷脂醯肌醇（ glycosylated derivative of
phosphatidylinositol; GPI ）結合蛋白質
Pass Test Questions
(B) 40. 下列何者不屬於膜上蛋白質之脂質錨定（ lipid anchor ）？
A. glycosyl phosphatidylinositol anchor
B. acetyl anchor
C. myristoyl anchor
D. thioether anchor
 Transport across the membrane

(1) Nonmediated transport: Simple Diffusion (Brownian

motion of molecules). Passive transport

(2) Facilitated transport: Accelerated Diffusion.

-Three general types of facilitated transport are known to
occur: Passive transport
1. through pores or channels
2. through carrier proteins
3. through permeases

(3) Active transport: transport against a concentration

gradient. Energy dependent
 Types of transport
 They include:
(a) Uniport
(b) Cotransport (include Symport and Antiport)
 (1) Nonmediated transport: Molecular diffusion
 Diffusion requires both a concentration gradient and membrane
permeability.

(2) Facilitate transport: Accelerated diffusion

 Three major ways for facilitated transport :
(a) Pores or channels Ionophores
(b) Carriers molecules
(c) Permeases
 Rate depends on the transporter amount.

Gramicidin A

Valinomycin
 Two features of ion channels
1. Ion selectivity
-Selectivity for a particular ion

2. Ion gating
-In response to gating stimulus (like pH, membrane potential, or
ligand), the switching between conductive and nonconductive
conformation is called ion gating.

Lys
Arg

Selectivity
filter Closed Opened
Na+/Leu transporter A model for voltage-gating in the K+ channel
 Permeases
 For transporting big molecules are called permeases (such
as amino acids, glucose and etc…).

 The permeases function require conformation changes.

 Active transport
 Substances are moved across a membrane against a
concentration gradient.
 Require ATP: by direct or indirect coupling of transport to ATP
hydrolysis.

E2 conformation (P)

E1 conformation

The functional cycle of the Na+–K+ pump

Pass Test Questions

(D) 5. 下列何種運送方式需要能量？
A. simple diffusion
B. facilitated diffusion.
C. osmosis
D. secondary active transport

(C) 43. 下列何者為中性（ neutral ）物質的穿膜促進性擴散作用（ facilitated

diffusion ）之特徵？
A. 這是一種需能反應
B. 主要依賴於膜電位（ membrane potential ）
C. 當代謝物濃度增加時，輸送速度會有上限
D. 以輸送速度與代謝物濃度作圖，將呈現線性圖

(D) 51. 下列有關於 facilitated diffusion 之敘述，何者錯誤？

A. 需要 carrier 媒介
B. 會飽和
C. 對某些化合物具選擇性
D. 需消耗能量
Pass Test Questions
(A) 42. 下列何者是細胞運送物質通過細胞膜之促進性擴散作用（ facilitated
diffusion ）的特性？
A. 受到溶質濃度梯度的驅動
B. 需要 ATP 的驅動
C. 通常是一種吸能的（ endergonic ）反應
D. 通常是一種不可逆的反應

(D) 41. 葡萄糖經由下列何種運輸方式，進入到紅血球內？

A. 主動運輸（ active transport ）
B. 反向運輸（ antiport ）
C. 電能單向運輸（ electrogenic uniport ）
D. 促進性擴散（ facilitated diffusion ）

(C) 43. 下列何者是配體管制型離子通道（ ligand-gated ion channel ）如菸

鹼性乙醯膽鹼受體（ nicotinic acetylcholine receptor ）的特性？
A. 在脂雙層中允許離子通透的帶電脂質
B. 碰到特定的離子時才允許配體通過細胞膜
C. 碰到特定的配體時才允許離子通過細胞膜
D. 配體與細胞膜上相對應受體結合需依賴特定離子存在
Pass Test Questions
(A) 91. 關於通過細胞膜的促進性擴散作用（ facilitated diffusion ），下列敘
述何者正確？
A. 經由專一性膜白質的作用，降低溶質通過細胞膜的活化能
B. 經由專一性膜白質的作用，增加擴散性溶質之穿膜濃度梯度的大
小
C. 被運載溶質的極性會影響脂雙層之特性
D. 細胞利用此機轉運輸氧氣，氮氣或甲烷等氣體通過細胞膜

(C) 95. 下列關於 ATP synthase 的敘述，何者錯誤？

A. 位於粒線體內膜
B. 使⽤粒線體內膜兩側的氫離⼦濃度差合成 ATP
C. ATP 會在粒線體內膜及外膜之間的間隙中形成
D. 合成 ATP 的過程中涉及 ATP synthase 之四級結構變化

(C) 47. 下列關於粒線體 ATP synthase 的敘述，何者錯誤？

A. 位於粒線體內膜
B. 可利用氫離子濃度梯度（ H+ gradient ）將 ADP 轉換為 ATP
C. 為氫離子與磷酸根之 symporter
D. 此酵素運作時會產生蛋白質四級結構變化
Pass Test Questions
(A) 91. 關於通過細胞膜的促進性擴散作用（ facilitated diffusion ），下列敘
述何者正確？
A. 經由專一性膜白質的作用，降低溶質通過細胞膜的活化能
B. 經由專一性膜白質的作用，增加擴散性溶質之穿膜濃度梯度的大
小
C. 被運載溶質的極性會影響脂雙層之特性
D. 細胞利用此機轉運輸氧氣，氮氣或甲烷等氣體通過細胞膜

(D) 91. 下列何種穿膜運輸作用是利用他種離子梯度當作能量來源？

A. 促進性擴散（ facilitated diffusion ）
B. 被動運輸（ passive transport ）
C. 初級主動運輸（ primary active transport ）
D. 次級主動運輸（ secondary active transport ）

(C) 65. 下列何者之濃度變化，最可能影響小腸對葡萄糖與胺基酸的吸收？

A. 血中胰島素
B. 血中鉀離子
C. 腸上皮細胞外之鈉離子
D. 腸上皮細胞外之鈣離子
 Utilization and Transport of Fat
Fats are insoluble in the aqueous media
 Bile salt: Emulsifier. It requires bile salt and takes place in
the duodenum.
1. Lipoproteins (soluble lipid and protein complex): transport
through the blood and lymphatic system.

Emulsification

脂肪小球
脂肪球
 Lipoproteins
 Lipoproteins are lipid–protein complexes.

 The lipoprotein complexes allow the transport of lipids to

tissue for energy storage or for oxidation.

 Cholesterol also use lipoprotein for transport and Utilization

 Classification of lipoproteins
 5 major lipoproteins are found in human.

 Chylomicron, very low-density lipoprotein (VLDL), intermediate-density

lipoprotein (IDL), low-density lipoprotein (LDL), and high density
lipoprotein (HDL). Each of them plays defined roles in lipid transport.

 These families are classified in terms of their density, as determined by

centrifugation.
Transport of Fat and Cholesterol
 LDL and Cholesterol Transport
 Cholesterol biosynthesis is confined primarily to the liver with
some occurring in intestine.
 LDL plays an important role in delivering cholesterol to other
tissue.

Familial hypercholesterolemia
( 家族性高膽固醇血症 ).

They demonstrate that cholesterol

uptake by cells is a receptor-
mediated process and the quantity
of receptors themselves is subject
to regulation.
 LDL receptors in cholesterol uptake
 Its requires Apo B-100 to interact with LDL receptor.
 The LDL receptor is recycled.
 The lysosomes digest LDL and release cholesterols for cholesterol
utilization or storage.

Lysosome

Endosome
 Chylomicron VLDL LDL HDL
Density Lowest Highest
Size Biggest smallest
origin Intestine Most from VLDL-IDL Liver,
liver intestine, and
plasma
Apoprotein ApoB-48, ApoB-100, ApoB-100
Apo-C Apo-C, Apo-E
Protein Lowest Highest
amount
Lipid amount Highest Lowest

Cholesterol Lowest Highest

amount
Function Transport Transport de Transport de Transport
dietary TG novo novo cholesterol
and synthesis TG synthesis back to liver
cholesterol and cholesterol
cholesterol
Pass Test Questions
(D) 44. 下列關於脂蛋白（ lipoprotein ）的敘述，何者錯誤？
A. 脂蛋白含脂質與蛋白質，它負責運送膽固醇（ cholesterol ）、磷
脂質（ phospholipid ）與三酸甘油酯（ triacylglycerol ）到各組織器官
B. ApoC-II 會促進血液中三酸甘油酯之分解
C. 含蛋白質量最多的脂蛋白是高密度脂蛋白（ HDL, high density
lipoprotein ）
D. 運送肝臟細胞所合成的三酸甘油酯到周邊組織的脂蛋白為乳糜微
粒（ chylomicrons ）

(D) 41. 肥胖是脂肪過多的疾病 , 關於脂肪組織之脂肪代謝 , 下列敘述何者錯誤？

A. 脂肪組織脂肪分解，釋放出來的脂肪酸，可供給其他組織產生能量
B. 脂肪組織脂肪分解，分解出來的脂肪酸，大部分仍在脂肪組織內合成三酸
甘油脂
C. 脂肪組織脂肪分解，釋放出來的脂肪酸可送到肝臟內再合成三酸甘油脂，
所以肥胖病患易合併脂肪肝
D. 空腹時 , 釋放出來的脂肪酸送到肝臟內合成三酸甘油脂 , 包裝成乳糜微粒
（ Chylomicron ）分泌至血液中
Pass Test Questions
(B) 44. 一種體染色體顯性（ autosomal dominant ）遺傳疾病稱為 familial hyper-
cholesterolemia 乃是因為 low density lipoprotein （ LDL ） receptor 突變所致。下列
有關 LDL 的敘述，何者正確？
A. LDL receptor 只存在肝細胞上
B. LDL 中的膽固醇經由 LDL receptor 之作用，可提供肝細胞合成 bile salts
C. LDL 所含的脂肪以 triglyceride 為主
D. LDL 是直接由肝臟製造分泌

(D) 79. 有關家族性高膽固醇血症（ familial hypercholesterolemia ）之敘述，下列何

者正確？
A. 主要是低密度脂蛋白結構異常引起的遺傳性疾病
B. 大多是低密度脂蛋白基因印記（ genomic imprinting ）異常所致
C. 大多是調控低密度脂蛋白表現的基因被甲基化（ methylation ）所致
D. 大多是低密度脂蛋白受器（ receptor ）基因突變引起的遺傳性疾病

(D) 42. 有關家族性高膽固醇症（ familial hypercholesterolemia ）最主要的致病原因

為何 ?
A. 飲食中過度高油脂食物的攝取
B. HMG-CoA reductase 基因變異
C. 正常 LDL receptor 蛋白表現量過高
D. LDL receptor 基因變異
Pass Test Questions
(A) 64. 有關脂肪的消化和吸收過程的敘述，下列何者錯誤？
A. 小於 10 個碳分子的脂肪酸主要由淋巴管匯集進入肝臟
B. 單酸甘油酯經擴散作用進入上皮細胞
C. 脂肪酸和單酸甘油酯在平滑內質網中變成三酸甘油酯
D. 腸上皮細胞內的三酸甘油酯可被蛋白質包覆

(D) 43. 關於脂肪組織之脂肪代謝，下列敘述何者錯誤？

A. 脂肪組織脂肪分解，釋放出來的脂肪酸，可供給其他組織產生能量
B. 脂肪組織脂肪分解，分解出來的脂肪酸，釋放至血液與血清白蛋白（
serum albumin ）結合
C. 脂肪組織脂肪分解，釋放出來的脂肪酸可送到肝臟內再合成三酸甘油
酯，所以肥胖病患易合併脂肪肝
D. 空腹時，釋放出來的脂肪酸送到肝臟內合成三酸甘油酯，包裝成乳糜
微粒（ chylomicron ）分泌至血液中

(A) 42. 下列何者與促進細胞攝取血液中膽固醇有關？

A. Apo B-100
B. Apo C-I
C. Apo C-II
D. lipoprotein lipase
Pass Test Questions
(B) 42. 下列關於脂質代謝的敘述，何者錯誤？
A. 細胞中合成膽固醇的前驅物為乙醯輔酶（ acetyl-CoA ）
B. 運送由食物攝取之三酸甘油酯（ triacylglycerol ）的主要脂蛋白
（
lipoprotein ），為超低密度脂蛋白（ VLDL , very low density
lipoprotein ）
C. 低密度脂蛋白（ LDL, low density lipoprotein ）主要功能是將膽
固醇送到周邊組織，易增加膽固醇在血管內壁堆積的風險，因此被稱為壞膽
固醇（ bad cholesterol ）
D. 胰島素可藉由活化 HMG-CoA reductase 而促進細胞中膽固醇的
生合成
 Membrane biosynthesis
Fat mobilization
(Lipolysis)

Fatty acid synthesis

b oxidation

Cholesterol metabolism
Steroids
&
Ketogenesis Vitamin D
 Fatty Acid metabolism
 Carnitine serves as a carrier to transport fatty acyl-CoA from
cytosol to mitochondrion for fatty acid oxidation.
 Citrate serves as a carrier to transport acetyl-CoA from
mitochondria to the cytosol for fatty acid synthesis.
Steps in b-oxidation of fatty acids

Step 1
Activation of fatty acids
(in cytosol)

Step 2
Transport of fatty acids
into mitochondria

Step 3
b-xidation
(in mitochondria matrix)
Transport of Fatty acyl-CoA into the mitochondria
matrix
Step 1: Carnitine interacts with fatty acyl-CoA yield fatty acyl-
carnitine via Carntine acyltransferase I.
Step 2: Fatty acyl-carnitine transverses the inner membrane through
translocase.
Step 3: Carnitine acyltransferase II exchanges fatty acyl-carnitine
for free carnitine and fatty acyl-CoA in the mitochondrial matrix

Translocase
 The importance of movement of fatty acyl-CoA
through the inner mitochondrial membrane

 The transportation of fatty acids into mitochondria is the rate-

limiting step for b-oxidation and is the primary point of regulation.

 It is regulated by controlling carntine acyltransferase I activity.

Carntine acyltransferase I is inhibited by malonyl-CoA, the first
committed intermediate in fatty acid synthesis.
 The b-oxidation pathway
Step I: Dehydrogenation
(Oxidation): require FAD and
generate 1 FADH2

Step II: Hydration ETC

Require H2O

Step III: Dehydrogenation

(Oxidation): Require NAD+ and ETC
generate 1 NADH

Step IV: Thiolysis: Form acetyl-

CoA and shorter fatty acyl-CoA TCA cycle
(2 carbon shorter each time).
Oxidation of fatty acid with odd-number carbon chain
 The propionyl-CoA has to be converted to succinyl-CoA
(a constitute of the citric acid cycle)

 ATP-dependent carboxylation of propionyl-CoA (by

propionyl-CoA carboxylase, ATP dependent)

(C3)

(C4)
 Ketogenesis
 It happens when carbohydrate intake is too low (fasting or
starvation). It causes acetyl-CoA accumulation.
 The “extra” acetyl-CoA is 2 Acetyl-CoA
converted to ketone bodies.
 It takes places in the liver
Acetoacetyl-CoA
mitochondria.
Acetyl-CoA
 Ketone bodies are
transported from liver to other HMG-CoA
tissues as an energy source
for tissues. Acetyl-CoA

spontaneous Acetoacetate NADH-depend reduction

Acetone b-hydroxybutyrate
ketone bodies
 Mobilization of the store fat (Lipolysis)
 The release of fats from adipose tissue is controlled hormonally to
met the needs of organism for energy generation.

 Three lipolytic enzymes are known to participate in this process:

1. Triacylglycerol lipase (also called hormone-sensitive lipase; HSL)
2. Adipose triglyceride lipase (ATGL).
3. Monoacylglycerol lipase (MGL).
 Fatty Acid synthesis
 Two main enzyme:
-Acetyl CoA carboxylase
-fatty acid synthase

 Cofactor:
-Biotin
-NADH

 The fatty acid synthesis depends on three separate enzymatic

systems:
(1) Biosynthesis of palmitate from acetyl-CoA
(2) Chain elongation starting from palmitate
(3) fatty acid desaturation
Fatty Acid synthesis (Anabolism)

 Each step of fatty acid

synthesis includes
cycles of four enzyme-
catalyzed steps:

1. Condensation of the
growing chain with
actived acetate
2. Reduction

3. Dehydration

4. Reduction.
 Rate-limiting step for fatty acid synthesis

 The formation of Malonyl-CoA is the first committed step

in fatty acid biosynthesis (An ATP-dependent, irreversible
reaction, requires biotin)

acetyl-CoA carboxylase
(ACC)
Pass Test Questions
(C) 90. 脂肪酸生合成之速率決定步驟（ rate-limiting step ）為：
A. 從 acetate 合成 acetyl-CoA
B. acetyl-CoA 與 malonyl-CoA 的縮合反應（ condensation ）
C. acetyl-CoA carboxylase 所催化合成 malonyl-CoA 的反應步驟
D. 使 malonate 轉變為 malonyl-CoA 的反應步驟

(B) 46. 下列關於脂肪酸的敘述 , 何者正確 ?

A. 血液中荷爾蒙 glucagon 可以促進細胞中脂肪酸的生合成
B. 細胞中脂肪酸的生合成過程中需要 NADPH 做為電子攜帶者
（ electron Carrier ）
C. 細胞中脂肪酸的生合成中間產物 malonyl-CoA 會活化粒線體外
膜上酵素（ carnitine acyltransferase I ）
D. 胰島素（ insulin ）可以增加血液中脂肪酸的濃度

(C) 40. 肝臟粒線體內 HMG-CoA synthase 合成酶的主要功能為下列何者？

A. 促進膽固醇合成 (Cholesterol biosynthesis)
B. 抑制脂肪酸合成 (Fatty acid biosynthesis)
C. 促進酮體合成 (Ketone body biosynthesis)
D. 促進糖質新生 (Gluconeogenesis ）
Pass Test Questions
(C) 34. 第一型糖尿病病人在極度缺乏胰島素及嚴重壓力下會產生 diabetic
ketoacidosis ，血中的 ketone bodies 濃度上升。下列相關敘述，何者錯誤？
A. ketone bodies 含 acetoacetic acid 及 β-hydroxybutyric acid
B. ketone bodies 由 acetyl-CoA 所形成
C. ketone bodies 是代謝酸，必須由呼吸及腎臟排出，無法被身體利用
D. ketone bodies 主要來源是脂肪酸分解而來的

(A) 41. 在人體中，屬於酮體（ ketone body ）成員之一的 acetoacetate ，主

要在下列那一個組織或器官中合成？
A. Liver
B. Intestinal mucosa
C. Adipose tissues
D. Kidney
(D) 90. 人體下列何組織較不會以酮體（ ketone bodies ）作為能量的來源 ?
A. 心臟
B. 腦
C. 肌肉組織
D. 肝臟
Pass Test Questions
(B) 92. 關於 acetyl-CoA carboxylase 在脂肪生成（ lipogenesis ）中的敘述，
下列何者錯誤？
A. 催化反應的產物之一為 malonyl-CoA
B. 反應過程需直接消耗 NADH
C. 催化的化學反應為脂肪酸合成的速率限制步驟
D. 肌肉中 AMP 上升時，經由活化 AMPK ，進而抑制 acetyl-CoA
carboxylase 的酵素活性
(D) 91.Carnitine palmitoyl transferases （ CPTs ）的損壞最可能會導致下列何
種物質無法直接進入粒線體中？
A. NADH
B. succinyl CoA
C. triacylglycerol
D. long-chain fatty acids

(B) 96. 下列那一類生化反應主要不是在粒線體內進行？

A. pyruvate oxidative decarboxylation
B. pentose phosphate pathway
C. oxidative phosphorylation
D. fatty acid β-oxidation
Pass Test Questions
(D) 93. 下列何種脂肪酸在進行 β-oxidation 時，需要 2,4-dienoyl-CoA
reductase 的參與？
A. Laurate
B. Palmitoleate
C. Oleate
D. linoleate
 (3 C2)
Cholesterol metabolism
condensation
 Cholesterol is synthesized in liver
cytosol. (C 6)
 All carbon atoms of cholesterol are from decarboxylation
acetyl-CoA.
(C 5)
 Cholesterol biosynthesis can be
separate into three processes:
condensation
1. Conversion of C2 fragments (acetyl-
CoA) to a C6 isoprenoid precursor
(mevalonate).
(C30)
2. Conversion of six C6 mevalonates, via
activated C5 intermediates, to the C30 cyclization
squalene.

3. Cyclization of squalene and its (C27)

transformation to the C27 cholesterol.
 The regulation of cholesterol synthesis
 Committed reaction:
Convert HMG-CoA to
Mevalonate (required
HMG-CoA reductase)

 HMG-CoA reductase is
an ER membrane
Committed reaction
protein with catalytic
unit hanging in the
cytosol.
Control of cholesterol
amount
1. Through controlling de
novo cholesterol
biosynthesis : the major
target for regulation of the
overall pathways (HMG-
CoA reductase).
(3) (1, major)
2. Through storing excess
cholesterol in the form of
cholesterol ester.

3. Through regulating the

synthesis of the LDL
receptor
(2)
 Regulation of HMG-CoA reductase
 Control of HMG-CoA reductase through transcriptional
and posttranslational regulation.

 Proteins that control HMG-CoA reductase activity are at

ER membrane.

 The central players:

- Insigs (Insulin-induced growth response genes)
- SREBP (Sterol regulatory element binding proteins)
- Scap (SREBP cleavage-activating proteins)
 Regulation of HMG-CoA reductase
-through transcriptional regulation
 When cholesterol levels in the cell are low, Scap and SREBP transport to
the Golgi.
 Membrane-bound proteases (S1P) releases SREBP’s transcription factor
domain (bHLH), which enters the nucleus and binds to sterol regulatory
elements (SRE) in the promoters of target genes.

 High levels of cholesterol block this process by Insig-mediated retention

of Scap–SREBP in the ER.

Low cholesterol
Express HMG-CoA
reductase and
LDL receptor
 Regulation of HMG-CoA reductase
- through ubiquitin-mediated proteolysis
 Sterol binding leads to rapid ubiquitin-proteasome degradation of
the HMG-CoA reductase.
Uniquitination complex
1 3

Sterol

2 4
 Statin
(1) They act by competitivelysinhibiting HMG-CoA reductase.

(2) It also leads to the increase production of LDL receptors and allows
more rapid clearance of extracellular cholesterol from the blood.
Thus, it decreases blood cholesterol level.
 The biological functions of cholesterol

 Cholesterol in the formation of lipid anchor proteins

(Prenylation).

 Cholesterol in the synthesis of bile acids

 Cholesterol in the synthesis of steroid hormones

 Lipid-soluble vitamins (Vitamin D)

Cholesterol in the synthesis of steroid hormones

Cholesterol
desmolase

 Cytochrome P450SCC/cholesterol side chain cleavage enzyme =

cholesterol desmolase=CYP11A1
 Pregnenolone (C21) is the precursor to all other known steroid
compounds.
 Cholesterol and vitamin D
 7-dehydrocholesterol is the
intermediate in cholesterol synthesis.

 On exposure to sunlight, the 7-

dehydrocholesterol is converted to
cholecalciferol (vitamin D3) in the
skin through UV photolysis.

 Liver makes 25-hydroxyvitamin D3

(Hydroxylation).

 Kidney makes 1, 25-dihydroxyvitamin

D3 (Hydroxylation).

 1, 25-dihydroxyvitamin D3 is the
active form of vitamin D.
Pass Test Questions
(B) 40. 下列關於固醇調節區域結合蛋白質（ sterol regulatory element-binding
protein ； SREBP ）之敘述，何者錯誤？
A. 位於內質網
B. 經由切斷連結的脂肪酸而活化
C. 活化後進入細胞核
D. 做為轉錄因子增加合成膽固醇（ cholesterol ）的基因表現

(C) 4. 膽固醇（ cholesterol ）進入目標細胞粒線體內層膜（ inner membrane ），係

經由何種酵素轉變成為妊烯醇酮（ pregnenolone ）？
A. 3β- 類固醇去氫酶（ 3β-hydroxysteroid dehydrogenase, 3β-HSD ）
B. 17α- 羥化酶（ 17α-hydroxylase ）
C. 膽固醇碳鏈酶（ cholesterol desmolase ）
D. 21β- 羥化酶（ 21β-hydroxylase ）

(C) 43. 下列關於細胞內膽固醇恆定的調控敘述，何者錯誤？

A. 膽固醇合成的關鍵性酵素為 HMG-CoA 還原酶（ HMG-CoA reductase ）
B. 細胞內膽固醇量過多時，可以活化 ACAT （ Acyl-CoA:cholesterol acyl
transferase ）使膽固醇進行酯化
C. 當細胞內缺乏膽固醇時，可以攝取葡萄糖直接促進膽固醇的合成
D. 細胞內膽固醇量過多時，細胞將抑制 LDL receptor 的表現，進而降低細胞
對血液中膽固醇的攝取量
Pass Test Questions
(B) 78. 膽固醇是下列何種維生素 (vitamin) 合成的前驅物 ?
A. A
B. D
C. E
D. K

(C) 57. 有關 vitamin D 的敘述，下列何者錯誤？

A. 主要經由皮膚在紫外線輻射下由 7- 脫氫膽固醇（ 7-dehydrocholesterol ）
轉
化而來
B. 其活性代謝產物會增加血漿中鈣離子濃度
C. 其活性代謝產物會降低血漿中磷酸鹽（ phosphate ）濃度
D. 其衍生物 19-nor-1α,25-dihydroxyvitamin D2 具有抑制副甲狀腺激素（
parathyroid hormone ; PTH ）的釋放作用

(A) 20. 下列何者是活化態維生素 D 的分子結構？

A. 1, 25-dihydroxycholecalciferol
B. 7-dehydrocholesterol
C. 25-hydroxycholecalciferol
D. cholecalciferol
 Pass Test Questions
(C) 45. Lovastatin 與 compactin 是用來治療家族性高膽固醇症（ familial
hypercholesterolemia ）的常用藥物，這兩種藥物主要是藉由抑制那一種酵素活性，進而
降低細胞內膽固醇的合成？
A. HMG-CoA synthase
B. HMG-CoA lyase
C. HMG-CoA reductase
D. HMG-CoA isomerase

(B) 42. 下列關於膽固醇代謝的敘述，何者錯誤？

A. 膽固醇是由乙醯輔酶 A （ acetyl-CoA ）生合成而來
B. 六碳結構 Mevalonate 是膽固醇的前驅物，每形成一個膽固醇需要 5 個分
子的 mevalonate
C. HMG-CoA reductase 是調控膽固醇合成的關鍵性酵素
D. 扮演不同生理功能的 bile acid ， vitamin D 與 estrogen 都是膽固醇的代謝
衍生產物

(D) 31. 有關「心臟病患血中膽固醇（ cholesterol ）過高而服用降膽固醇藥物 statin ，會

影響 SREBP （ sterol response element binding protein ）之作用」，下列何者錯誤？
A. 肝細胞中 SREBP 會由 ER 釋放出來
B. LDL receptor 基因表現會增加
C. 血液中 LDL-cholesterol 會下降
D. SREBP 只調控與膽固醇代謝相關的基因
Pass Test Questions
(C) 69. 人體內， vitamineD3 轉為 25-hydroxycholecalciferol 主要在下列哪
種器官中進行？
A. Skin
B. kidney
C. Liver
D. Parathyroid gland
(C) 92.Statins 是用來治療家族性高膽固醇血症（ familial
hypercholesterolemia ）的常用藥物，這類藥物主要是藉由抑制那一種酵素
活性，進而降低細胞內膽固醇的合成？
A.β-hydroxy-β-methylglutaryl-CoA （ HMG-CoA ） synthase
B.β-hydroxy-β-methylglutaryl-CoA （ HMG-CoA ） lyase
C.β-hydroxy-β-methylglutaryl-CoA （ HMG-CoA ） reductase
D.β-hydroxy-β-methylglutaryl-CoA （ HMG-CoA ） isomerase
(C) 90. 下列何者並非膽固醇（ cholesterol ）生合成之前驅物？
A. 乙酸（ acetate ）
B. 異戊二烯（ isoprene ）
C. 二氫鞘氨醇（ sphinganine ）
D. 鯊烯（ squalene ）
Pass Test Questions
(C) 69. 人體內， vitamineD3 轉為 25-hydroxycholecalciferol 主要在下列哪
種器官中進行？
A. Skin
B. kidney
C. Liver
D. Parathyroid glan

(D) 69. 有關維生素 D3 （ vitamin D3 ）的敘述，下列何者最為適當？

A. 又稱為 25-hydroxycholecalciferol
B. 在肝臟製造合成
C. 維生素 D3 經 1α-hydroxylase 作用，形成有活性的代謝產物
D. 維生素 D3 可由食物中攝取補充

(A) 92. 有關家族性高膽固醇症（ familial hypercholesterolemia ）的敘述，

下列何者最不正確？
A. LDL receptor 過度表達
B. LDL 的濃度太高
C. LDL receptor 基因突變
D. LDL receptor 運送到細胞膜過程受阻
Nucleotide metabolism
 Significances of nucleotides
 They are precursors of DNA and RNA.

 They are energy currency in metabolic transactions (ATP,

GTP).

 They are components of:

-Cofactors: such as NAD, NADPH, FAD, S-
adenosylmethionine (SAM), and coenzyme A

-Activated biosynthetic intermediates: such as UDP-

glucose (drives carbohydrate metabolism), and CDP-
diacylglycerol, CDP-choline (drives lipid metabolism)

-Second messengers: such as cAMP and cGMP

 Nucleotide
(Nucleobase)

4 1
3 2

Lack a 2’-OH group

 Overview of nucleotide metabolism

 De novo pathways: Most of organisms can synthesize

purine and pyrimidine nucleotide from low-molecular-
weight precursors (ex: liver and intestine).
-It requires a lots of energy!!!

 Salvage pathways: Most of organisms can also synthesize

nucleotides from nucleosides or bases that become
available either in the diet or through enzymatic
breakdown of nucleic acids (ex: brain).
-Save energy!!!
De novo pathway of nucleotide biosynthesis

low-molecular-
weight precursors
 Overview of nucleotide metabolism
 Salvage pathways: The reutilization of nucleosides and nucleobases

b-Alanine
5-phospho-a-D-ribosyl-1-pyrophosphate (PRPP) is the
central metabolite in de novo and salvage pathway

PRPP, an activated ribose

De Novo pathway Salvage pathway

PRPP + amino acids + PRPP +
ATP + CO2 +…… free nucleobase

PPi
Nucleotide Nucleotide
 The synthesis of PRPP
 It requires ATP

 It is formed through the action of PRPP synthetase, which

activates carbon 1 of ribose-5-phosphate.

1
5 1 5
 Pass Test Questions
(D) 80. 下列何者為核苷酸（ nucleotide ）重新合成路徑（ de novo synthesis ）
及補救合成路徑（ salvage pathway ）皆會使用的重要代謝物？
A. glycinamide ribonucleotide （ GAR ）
B. 5-phosphoribosylamine （ PRA ）
C. formylglycinamide ribonucleotide （ FGAR ）
D. 5-phospho-α-D-ribosyl-1-pyrophosphate （ PRPP ）
Purine Metabolism
 Generation of IMP
 Inosinic acid (Inosine-5’-monophosphate; IMP): The first fully
formed purine nucleotide (11 step reaction).

Hypoxanthine

11 step
reaction
 Generation of IMP
 The atoms of purine ring are contributed by a number of compounds
including amino acids (aspartate, glycine and glutamine), CO2, and
tetrahydrofolate (10-Formyl-tetrahydrofolate).
 Regulatory step
-It requires PRPP amidotransferase
-High amount of AMP, GMP, ADP, and GDP amount inhibit the
reaction

Purine ring

IMP
IMP GMP
Gln, ATP

GMP
IMP synthetase
dehydrogenase

AMP
IMP
Asp, GTP

Adenylosuccinat
e synthetase
Regulatory control of IMP to GMP and AMP
-The reciprocal control of production
De Novo biosynthesis of purine nucleotides

Gln, Asp, Gly, CO2, 10-fomyl-THF, ATP

Rate limiting step: PRPP amidotransferase

Asp, GTP Gln, ATP

Nucleoside diphosphate
kinase
 Salvage pathway of purine nucleotides
 A phosphoribosyl transferase reaction catalyzes the
transfer of a free base to the ribose of PRPP, displacing
pyrophosphate and producing a nucleoside
monophosphate (nucleotide).

Phosphoribosyl
transferase

Activated PRPP + Nucleobase Nucleotide

 Salvage pathway of purine nucleotides
 Two specific enzyme systems (phosphoribosyltransferases) catalyze
the transfer of ribose phosphate from PRPP to free purine base.

 HGPRT: hypoxanthine-guanine
phosphoribosyltransferase.

 APRTase: adenine
phosphoribosyltransferase
 Purine degradation
 Purine degradation leads to form of xanthine and uric acid.
Strategy

Nucleotides

Nucleotidase

Nucleosides
Purine
nucleoside
phosphorylase
(PNP)
Free nucleobases

Uric acids
 Xanthine to Uric acid
 Xanthine is the point of convergence for the metabolism of the purine
bases (Xanthine  Uric acid)

 It requires Xanthine dehydrogenase.

 Purine ribonucleotide degradation pathway is same for purine

deoxyribonucleotides.
 Excessive accumulation of uric acids: Gout
 The high concentration of uric acids: cause hyperuricemia ( 高
尿酸血症 , 0.3% in North America and Europe).

 Prolonged or acute elevation of blood urate leads to its

precipitation, as crystals of sodium urate, in the synovial fluid
of joints. (inflammation and arthritis).
 Salvage of purines and Lesch-Nyhan Syndrome
 Lesch-Nyhan Syndrome is a sex-linked recessive trait
because the HGPRT (HPRT1 gene) is at X chromosome.
萊希 - 尼亨症候群
 Allopurinol and gout
 A structural analog of hypoxanthine. Allopurinol strongly inhibits
Xanthine dehydrogenase.
 This inhibition causes accumulation of hypoxanthine and
xanthine, both of which are more soluble.

Allopurinol
 Pass Test Questions
A) 32. 5-phosphoribosyl-1-pyrophosphate （ PRPP ）合成 inosine 5'-
monophosphate （ IMP ）的核苷酸生合成途徑中， PRPP amidotransferase 反
應速率可受到下列那一個產物的直接負調控？
A. AMP
B. CMP
C. FAD
D. Malonyl-CoA

(C) 80. 下列那一個分子最不可能經由嘌呤回收（ purine salvage ）途徑再利用？

A. adenine
B. guanine
C. xanthine
D. hypoxanthine

(A) 45. Lesch-Nyhan syndrome 是因缺乏次黃嘌呤－ 鳥嘌呤磷酸核苷轉移酶（

hypoxanthine-guaninephosphoribosyltransferase ），因而發生下列何種現象？
A. 大量嘌呤（ purine ）生合成
B. 大量 dTTP 合成
C. 在血液中 dCTP 量非常低
D. 尿液出現大量尿素（ urea ）
 Pass Test Questions
(D) 31. 下列關於痛風（ Gout ）的敘述，何者錯誤？
A. 當嘌呤代謝出現異常時，累積過多的尿酸而導致
B. 關節會因累積過多的尿酸鈉鹽晶體（ sodium urate crystals ）而發
炎疼痛
C. Allopurinol 會抑制 xanthine oxidase ，使得嘌呤的代謝物以水溶性
的
xanthine 和 hypoxanthine 形式排出
D. Allopurinol 在痛風急性發作時可以直接抑制發炎反應，緩解疼痛

(B) 31. 下列關於 Lesch-Nyhan syndrome 的敘述 , 何者錯誤？

A. 先天缺乏 Hypoxanthine-guanine phosphoribosyltransferase 而導
致
B. 無法藉由新合成路徑（ De novo pathway ）合成鳥糞嘌呤
C. 患病兒童通常在 2 歲前發病 , 出現肢體不協調與智能障礙
D. 嚴重者會累積過多的尿酸 , 造成組織的破壞
(C) 93. 下列何種胺基酸可作為基質（ substrate ）參與尿素（ urea ）、嘌呤
（ purine ）或嘧啶（ pyrimidine ）的合成？
A. 甲硫胺酸（ methionine ）
B. 離胺酸（ lysine ）
C. 天門冬胺酸（ aspartate ）
 Pass Test Questions
(B) 79. 下列何種反應是一種 deamination 的作用？
A. 胞嘧啶（ cytosine ）變成次黃嘌呤（ hypoxanthine ）
B.5'- 甲基胞嘧啶（ 5'-methylcytosine ）變成胸腺嘧啶（ thymine ）
C. 腺嘌呤（ adenine ）變成黃嘌呤（ xanthine ）
D. 鳥糞嘌呤（ guanine ）變成尿嘧啶（ uracil ）

(B) 80. 下列何種酵素與尿酸堆積及痛風發生最為相關？

A. adenine phosphoribosyltransferase
B. 5-phospho-α-D-ribosyl-1-pyrophosphate synthetase
C .glucose 6-phosphatase
D. orotate phosphoribosyltransferase
 Pyrimidine Nucleotide Metabolism
 Uridine Monophosphate (UMP) is synthesized first.
 The pyrimidine pathway is un-branched
UMP  UDP  UTP  CDP  CDP  CTP

Glutamine

CO2
Glutamine and CO2 Sources of carbon atoms
in pyrimidine rings
 Control of pyrimidine synthesis

1. Aspartate transcarbamoylase
(ATCase): The enzyme is
inhibited by CTP and activated
by ATP.

CTP synthetase

2. CTP synthetase: The enzyme is

inhibited by CTP and activated by GTP.
 Degradation of Pyrimidines
(CMP and UMP)

Pyrimidines are degraded to uracil

Uracil reduced in liver, forming b-

Ureidopropionic acid or b-alanine.

(1) They are converted to malonyl-CoA 

fatty acid synthesis for energy
metabolism.

(2) b-alanine can be used in the

biosynthesis of coenzyme A.
 Deoxyribonucleotide Biosynthesis and Metabolism
 One enzyme, ribonucleotide reductase (rNDP reductase),
reduces all four ribonucleotides to their 2-deoxyribose
derivatives.
Biosynthesis of thymine deoxyribonucleotides
(1) De novo

Thymidylate
synthase
dUMP

(2) salvage
From
Thymidine 5, 10-Methyle-THF
kinase
 5-Fluorouracil (FUra)
 A target enzyme for chemotherapy because cancer cells requires
dTTP for their proliferation.
 Those compounds form dUMP analog that can function as an
irreversible inhibitor of TS.
 Some of chemotherapeutic drugs are indicated by
blocking the conversion of DHF to THF.
 Pass Test Questions
(C) 30.RNA 降解後， CMP 與 UMP 主要會被代謝成下列那一個中間產物？
A.β-aminoisobutyrate
B.thymine
C.uracil
D.hypoxanthine

(D) 30. 抗癌藥 5-Fluorouracil 可減少細胞中之 dTMP 的供應，因而抑制 DNA

合成，其作用機轉是因為此藥物之衍生物可直接抑制下列何種酵素之活性？
A. Dihydrofolate reductase
B. Ribonucleotide reductase
C. Thymidine kinase
D. Thymidylate synthase

(D) 29. 去氧月尿苷（ deoxyuridylate, dUMP ）轉變為胸苷（ thymidylate,

dTMP ）之酶反應需要何種輔酶參與？
A. Coenzyme A
B. Biotin
C. S-adenosylmethionine
D. N5, N10-methylenetetrahydrofolate
Pass Test Questions
(C) 90. 下列何者不是細胞內 acetyl-CoA 的主要來源？
A. Fatty acids
B. Ketogenic amino acids
C. Pyrimidine
D. Pyruvate
(B) 79. 下列那一個官能基出現在胸腺嘧啶（ thymine ）而不出現在尿嘧啶
（ uracil ）？
A. 去氧核糖（ deoxyribose ）
B. 甲基（ -CH3 ）
C. 胺基（ -NH2 ）
D. 核糖（ ribose ）
 Amino acid metabolism
Metabolic uses of amino acids

 Building blocks for

protein synthesis

 Precursors of
Nucleotides and
Heme

 Source of energy
(TCA cycle)
The degradation and recovery of amino acid
 Degradation of Carbon skeletons
 Glucogenic amino acids are amino acids whose carbon skeletons
are degraded to one of these five intermediates.
• Pyruvate
• a-Ketoglutarate
• Succinyl-CoA TCA cycle (Glucogenesis)
• Fumarate
• Oxaloacetate
 Ketogenic (Lipogenic) amino acids are amino acids whose
carbon skeletons are degraded to: ketone bodies
• Acetoacetate
Ketone body(ketogenesis)
• Acetyl-CoA

 Some amino acids are both glucogenic and ketogenic.

Degradation of Carbon skeletons
 Transamination reaction of amino acids
 Amino acids lose their α-amino group (α-NH2 group) through
transamination, that is, transfer to an α-keto acid ( 酮酸 , ususally
α-ketoglutarate).

 Transamination is reversible and is mediated by several different

aminotransferase enzymes and the coenzymes.
Example:

Aminotransferase
PLP

Coenzymes
(amino acid1) (α-keto acid1) (Vitamin B6) (α-keto acid2) (amino acid2)
 Pyridoxal phosphate (PLP)
Vitamin B6
 Vitamin B6 is also called pyridoxine.

 The active coenzyme has been

oxidized to an aldehyde and the
hydroxymethyl group at position 5 is
phosphorylated.

 Pyridoxal phosphate (PLP) is the

predominant coenzyme form

 Pyridoxamine phosphate (PMP) is an

intermediate form in transamination
reactions.
 Amino acids that produce oxaloacetate
 Amino acids: Asparagine and
Aspartate.

 A PLP- dependent transamination

PLP
Amino acids that produce pyruvate
 Serine: transamination.

 Alanine: dehydration and transamination.

 Amino acids that produce pyruvate

 Glycine carbon skeleton

becomes Pyruvate via Serine.

 It is THF and PLP-dependent.

 THF provide methyl group.

Transamination
Amino acids that produce a-ketoglutarate
 Glutamine to a-ketoglutarate via Glutamate

glutaminase

Deamination
Or
Transamination
Amino acids that produce a-ketoglutarate

Glutamate
Amino acids that produce Succinate

Succinyl-CoA
 Nitrogen disposal

 Nitrogen accruing outside the liver is transported to the

liver as glutamine (in most tissues ) or alanine (in
muscle).

 In the liver, nitrogen is released as free ammonia.

Ammonia is then incorporated into urea.

 Urea is released from the liver into the bloodstream and

excreted through the kidneys.
Nitrogen disposal
The urea cycle spans mitochondria and cytosol in
liver
Amino Acid Biosynthesis Overview
An overview of amino acid metabolism
Dietary protein Body protein

Protein Synthesis of
Amino acid
synthesis N-compound

a-ketoglutarate

Transamination

Glutamate
Deamination
NH3
Keto acids

Urea
Energy Glucose Fat Non-essential
Amino acids
 Pass Test Questions
(C) 44. 胺基酸代謝須進行轉氨反應，此反應最常需要那一種維生素參與？
A. Vitamin B1 （ Thiamine ）
B. Vitamin B2 （ Riboflavine ）
C. Vitamin B6 （ Pyridoxine ）
D. Vitamin B12 （ Cobalamin ）

(B) 44. 那一種胺基酸生合成過程中， tetrahydrofolate 會轉變成 N5, N10-

methylenetetrahydrofolate ？
A. serine+homocysteine → cysteine+alpha-ketobutyrate
B. serine → glycine
C. glutamate → glutamine
D. glutamate → proline

(D) 93. 在哺乳類細胞中， N5- 甲基四氫葉酸 (N5-methyl tetrahydrofolate; N5-

methyl H4 folate) 直接參與下列哪一種氨基酸生合成？
A. Isoleucine
B. Leucine
C. lysine
D. Methionine
 Pass Test Questions
(B) 93. 下列有關尿素循環（ urea cycle ）的敘述 , 何者錯誤？
A. 尿素循環主要於肝臟中進行
B. 尿素循環的產物之一為草醯乙酸（ oxaloacetate ）
C. 尿素循環的一部分反應於粒線體內進行，另一部分反應則在細胞質
中進行
D. 在人體中，尿素循環可將含氮的代謝物轉變為尿素

(B) 44. Ammonium ion （ NH4+ ）可藉由下列何種方式，由骨骼肌細胞運送到

肝細胞代謝？
A. Krebs cycle
B. glucose-alanine cycle
C. urea cycle
D. citric acid cycle

(B) 41. free ammonia 在細胞內可藉由那一個酵素作用 , 將其轉化為無毒性的

L-glutamine?
A. glutaminase
B. glutamine synthetase
C. glutamate dehydrogenase
D. aspartate aminotransferase
 Pass Test Questions
(C) 43. 克氏循環（ TCA cycle ）的中間產物可經由轉氨基作用
（ transamination ）直接生成下列那兩種胺基酸？
A. 精胺酸（ arginine ）與組胺酸（ histidine ）
B. 酪胺酸（ tyrosine ）與脯胺酸（ proline ）
C. 麩胺酸（ glutamate ）與天冬胺酸（ aspartate ）
D. 丙胺酸（ alanine ）與絲胺酸（ serine ）

(D) 94. 胺基酸最主要是經由下列何種代謝路徑間接產生葡萄糖（ glucose ）？

A. pentose phosphate pathway
B. urea cycle
C. oxidative phosphorylation
D. citric acid cycle

(A) 47. 下列那一個胺基酸可以降解成 pyruvate ？

A. alanine
B. leucine
C. lysine
D. tyrosine
 Pass Test Questions
(D) 44. 腦中核酸分解所形成之氨（ ammonia ），主要轉化為下列何種物質，
再經由血液運送至肝臟或腎臟？
A. 尿酸（ uric acid ）
B. 尿素（ urea ）
C. 天冬醯胺（ asparagine ）
D. 麩胺醯胺（ glutamine ）

(A) 93. 下列何種物質可經由轉氨基作⽤（ transamination ）直接合成 glutamic

acid ？
A. α-ketoglutarate
B. Pyruvate
C. Acetoacetate
D. Oxaloacetate
(A) 93.Aspartate-argininosuccinate shunt 是代謝胺基酸之重要途徑，其與下列
那兩種代謝環之連結有關？
A.citric acid cycle 和 urea cycle
B.urea cycle 和 Cori cycle
C.citric acid cycle 和 glyoxylate cycle
D.glucose-alanine cycle 和 urea cycle
 Pass Test Questions
(D) 99. 下列何者兼具必需胺基酸（ essential amino acid ）及生酮性胺基酸
（ ketogenic amino acid ）特性？
A. 天門冬胺酸（ aspartate ）
B. 組胺酸（ histidine ）
C. 酪胺酸（ tyrosine ）
D. 白胺酸（ leucine
(C) 92. 下列關於 Cori cycle 在體內不同組織進行反應的敘述，何者正確？
A. 乳酸（ lactate ）由肝臟運送到骨骼肌
B. 葡萄糖由骨骼肌運送到肝臟
C. 肝臟經過糖質新生（ gluconeogenesis ）產生葡萄糖
D. 骨骼肌經過糖質新生（ gluconeogenesis ）產生乳酸

(D) 95. 胺基酸在肌肉組織中代謝產生的氨（ ammonia ）會再以何種胺基酸型式

攜帶進入肝臟進行代謝？
A. 離胺酸（ lysine ）
B. 瓜胺酸（ citrulline ）
C. 精胺酸（ arginine ）
D. 丙胺酸（ alanine ）
 Pass Test Questions
(D) 94. 下列有關琥珀酸–甘胺酸路徑（ succinate-glycine pathway ）的敘述，
何者錯誤？
A. 此路徑作用的第一個酵素為 δ-aminolevulinic acid synthase （ ALA
synthase ）
B. 血基質（ heme ）中的碳原子來自琥珀酸（ succinate ）及甘胺酸
（ glycine ）
C. 需要磷酸吡哆醛（ pyridoxal phosphate ）參與作用
D. 血基質（ heme ）合成在細胞質中完成

(D) 78. 胺基酸的代謝需要有多重輔因子（ cofactors ）參與，下列那一種輔因子不能作為

單一碳基團（ one carbonmoiety ）供給者或傳送者？
A. tetrahydrofolate
B. Biotin
C. S-adenosylmethionine
D. pyridoxal phosphate