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Chapter 4
Carbohydrates Metabolism
§ 1 Overview
• Carbohydrates in general are
polyhydroxy aldehydes or ketones
or compounds which yield these on
hydrolysis.
Biosignificance of Carbohydrates
• The major source of carbon atoms and
energy for living organisms.
• Supplying a huge array of metabolic
intermediates for biosynthetic reactions.
• The structural elements in cell coat or
connective tissues.
Glucose transporters
(GLUT)
• GLUT1~5
GLUT1: RBC
GLUT4: adipose tissue, muscle
The metabolism of
glucose
•
•
•
•
•
glycolysis
aerobic oxidation
pentose phosphate pathway
glycogen synthesis and catabolism
gluconeogenesis
glycogen
Glycogenesis
Glycogenolysis
starch
lactate
glucose
Lactate,
amino
acids,
glycerol
H2O+CO2
Pentose phosphate
pathway
Ribose, NADPH
§2 Glycolysis
Glycolysis
• The anaerobic catabolic pathway by
which a molecule of glucose is broken
down into two molecules of lactate.
glucose →2lactic acid (lack of O2)
• All of the enzymes of glycolysis locate
in cytosol.
1. The procedure of glycolysis
G
glycolytic pathway
pyruvate
lactic acid
1) Glycolytic pathway :
G → pyruvate
including 10 reactions.
glucose 6-phosphate
HO CH2
H
H
OH
O
H
OH
H
H
OH
ATP
ADP
2+
Mg
Hexokinase
OH
G
P O CH2
H
H
OH
O
H
OH
H
OH
H
OH
G-6-P
• Phosphorylated G cannot get out of cell
• Hexokinase , HK (4 isoenzymes) ,
glucokinase, GK in liver ;
• Irreversible .
Comparison of hexokinase and
glucokinase
hexokinase
glucokinase
occurrence in all tissues
only in
liver
Km value
0.1mmol/L
10mmol/L
Substrate
G, fructose,
mannose
glucose
(2) G-6-P → fructose 6-phosphate
P O CH2
H
H
OH
P O CH2
O H
H
H
OH
OH
H
O
OH
G-6-P
isomerase
CH2OH
OH
OH
H
OH
H
F-6-P
(3) F-6-P → fructose 1,6bisphosphate
P O CH2
O
PFK-1
OH
H
OH
H
OH
P O CH2
CH2OH
H
F-6-P
H
Mg2+
ATP
CH2 O P
O
OH
OH
H
ADP
OH
H
F-1,6-BP
• The second phosphorylation
• phosphofructokinase-1, PFK-1
(4) F-1,6-BP → 2 Triose
phosphates
CH2 O P
C O
HO C H
H C OH
CH2 O P
C O
aldolase
H C OH
CH2 O P
F-1,6-BP
• Reversible
CH2OH
CHO
+
CHOH
CH2 O P
dihydroxyacetone glyceraldehyde
3-phosphate,
phosphate,
GAP
DHAP
(5) Triose phosphate
isomerization
CH2 O P
C O
CH2OH
DHAP
CHO
phosphotriose
isomerase
CHOH
CH2 O P
GAP
G→2 molecule glyceraldehyde-3-phosphate,
consume 2 ATP .
(6) Glyceraldehyde 3-phosphate
→
glycerate 1,3-bisphosphate
CHO
CHOH
CH2 O P
glyceraldehyde
3-phosphate
Pi NAD+
NADH+H +
glyceraldehyde
3-phosphate
dehydrogenase,
GAPDH
O C O~ P
CHOH
CH2 O P
glycerate
1,3-bisphosphate,
1,3-BPG
(7) 1,3-BPG → glycerate 3phosphate
O C O~ P
CHOH
CH2 O P
glycerate
1,3-bisphosphate
ADP
ATP
Phosphoglycerate
kinase
COOCHOH
CH2 O P
glycerate
3-phosphate
• Substrate level phosphorylation
(8) Glycerate 3-phosphate →
glycerate 2-phosphate
COO-
-
COO
CHOH
CH2 O P
glycerate
3-phosphate
Mutase
CH O P
CH2OH
glycerate
2-phosphate
(9) Glycerate 2-phosphate →
phosphoenol pyruvate
COOCH O P
enolase
CH2OH
glycerate
2-phosphate
COOC O ~ P + H2O
CH2
PEP
(10) PEP →pyruvate
COO
-
C O~ P
CH2
PEP
ADP
ATP
pyruvate kinase
COOC O
CH3
Pyruvate
• Second substrate level phosphorylation
• irreversible
2) Pyruvate → lactate
NADH + H+
COO
C O
CH3
Pyr
NAD+
COO
CHOH
Lactate dehydrogenase,
CH3
LDH
Lactic acid
Summary of Glycolysis
ADP
ADP
ATP 2+
ATP 2+
Mg
Mg
F- 6-P
F- 1,6-BP
G
G-6-P
HK
Isomerase
PFK-1
Aldolase
lactate
NAD+
DHAP
GAP
LDH
H3PO4
NAD+
glyceraldehyde
NADH+H+
pyruvate
3-phosphate
+
NADH+H
dehydrogenase
ATP
pyruvate kinase
ADP
PEP
glycerate
1,3-bisphosphate
ADP
Enolase
ATP
Mutase
glycerate
glycerate
H2O
2-phosphate
3-phosphate
Phosphoglycerate
kinase
Total reaction:
C6H12O6 + 2ADP + 2Pi
2CH3CHOHCOOH + 2ATP + 2H2O
Formation of ATP:
The net yield is 2 ~P or 2 molecules of ATP
per glucose.
2. Regulation of Glycolysis
• Three key enzymes catalyze
irreversible reactions : Hexokinase,
Phosphofructokinase & Pyruvate
Kinase.
1) PFK-1
The reaction catalyzed by PFK-1 is
usually the rate-limiting step of the
Glycolysis pathway.
This enzyme is regulated by covalent
modification, allosteric regulation.
bifunctional
enzyme
2) Pyruvate kinase
• Allosteric regulation:
F-1,6-BP acts as allosteric activator；
ATP and Ala in liver act as allosteric
inhibitors;
• Covalent modification:
phosphorylated by Glucagon
through cAMP and PKA and inhibited.
ATP
Pyruvate Kinase
(active)
ADP
PKA
cAMP
Glucagon
Pyruvate Kinase- P
(inactive)
3) Hexokinase and
glucokinase
• This enzyme is regulated by covalent
modification, allosteric regulation and
isoenzyme(同工酶) regulation.
• Inhibited by its product G-6-P.
• Insulin induces synthesis of glucokinase.
3. Significance of glycolysis
1) Glycolysis is the emergency energyyielding pathway.
2) Glycolysis is the main way to
produce ATP in some tissues, even
though the oxygen supply is sufficient,
such as red blood cells, retina, testis,
skin, medulla of kidney.
•
In glycolysis, 1mol G produces 2mol
lactic acid and 2mol ATP.
§ 3 Aerobic Oxidation of
Glucose
• The process of complete oxidation
of glucose to CO2 and water with
liberation of energy as the form of
ATP is named aerobic oxidation.
• The main pathway of G oxidation.
1. Process of aerobic
oxidation
cytosol
first
stage
G
Pyr
glycolytic
pathway
Mitochodria
third
second
stage
stage
Pyr
CH3CO~SCoA
CO2 + H2O+ATP
TAC
1) Oxidative decarboxylation
of Pyruvate to Acetyl CoA
-
COO
NAD+
C O + HSCoA
CH3
NADH + H + O
Pyruvate
dehydrogenase
complex
pyruvate
• irreversible;
• in mitochodria.
H3C C ~SCoA + CO2
Acetyl CoA
Pyruvate dehydrogenase complex:
E1 pyruvate dehydrogenase
Es E2 dihydrolipoyl transacetylase二氢硫辛酸转乙酰
酶
E3 dihydrolipoyl dehydrogenase二氢硫辛酸脱氢酶
thiamine pyrophosphate, TPP (VB1)
HSCoA (pantothenic acid)
cofactors
lipoic Acid
NAD+ (Vpp)
FAD (VB2)
Pyruvate dehydrogenase complex:
HSCoA
NAD+
The structure of
pyruvate dehydrogenase complex
N
H3C C
N
NH2
C
HC
C
C
H
S
N
C
H2
O-
+
O-
C
CH2CH2 O
P
O P
C
CH3
O
O
O-
TPP
H2
C
+2H
CH (CH2)4 COOH
H2C
S
H2
C
S
lipoic acid
-2H
H2C
SH
CH (CH2)4 COOH
SH
dihydrolipoic acid
HSCoA
4'-phosphopantotheine
OH CH3
HS CH2 CH2 NH C CH2 CH2 NH C C
O H
O
¦Â-mercaptoethylamine
¦Â-alanine
OH
OH
C CH2 O P O P O 3'AMP
CH3
O
O
pantoic acid pyrophosphate
pantothenic acid
CO2
NADH
+H+
NAD+
CoASH
2) Tricarboxylic acid cycle, TCAC
The cycle comprises the combination of a
molecule of acetyl-CoA with oxaloacetate,
resulting in the formation of a six-carbon
tricarboxylic acid, citrate. There follows a
series of reactions in the course of which
two molecules of CO2 are released and
oxaloacetate is regenerated.
Also called citrate cycle or Krebs cycle.
(1) Process of reactions
CH3CO~SCoA
acetyl CoA HSCoA
H2O
CH2 COO
CH2 COO
CO COO
CH2 COO
oxaloacetate
NADH+H+
H2O
HO C
citrate
synthase
COO
CH2 COO
CH
COO
cis-aconitate
citrate
+
aconitase
NAD
HO CH
COO
malate
CH2 COO
Citrate cycle
COO
isocitrate CH
HO CH
fumarate
succinate
COO
isocitrate dehydrogenase
succinyl CoA
syntetase
CH2 COO
NADH+H+
NAD+
CO~ SCoA
CH2 COO
CH2
CH2
CoASH GTP GDP+Pi
CO2
NADH+H+
succinate dehydrogenase
CH2 COO
COO
NAD+
OOC CH
FAD
CH2 COO
H2O
CH2 COO
fumarase
HC
FADH2
COO
aconitase
malate dehydrogenase
H2O
C
CO2
HSCoA
COCOO
succinyl-CoA ¦Á-ketoglutarate ¦Á-ketodehydrogenase glutarate
Summary of
Krebs Cycle
①
Reducing
equivalents
② The net reaction of the TCAC:
acetylCoA+3NAD++FAD+GDP+Pi+2H2O
→ 2CO2+3NADH+3H++FADH2+GTP+
HSCoA
③ Irreversible and aerobic reaction
④ The enzymes are located in the
mitochondrial matrix.
⑤ Anaplerotic reaction of
oxaloacetate
ADP + Pi
ATP
CH3
Biotin
C H2
C O + CO2
pyruvate carboxylase
COOH
CH3
COOH
C
O
COOH
NADPH+H+
C O + CO2
COOH
+
NADP
COOH
NAD+
NADH+H+
C H2
C H2
malic enzyme
CHOH
COOH
COOH
malic acid DH
C
O
COOH
(2) Bio-significance of TCAC
① Acts as the final common pathway for
the oxidation of carbohydrates, lipids,
and proteins.
② Serves as the crossroad for the
interconversion among carbohydrates,
lipids, and non-essential amino acids,
and as a source of biosynthetic
intermediates.
Krebs Cycle is at the
hinge of metabolism.
2. ATP produced in the aerobic
oxidation
• acetyl CoA → TCAC : 3 (NADH+H+) +
FADH2 + 1GTP → 12 ATP.
• pyruvate →acetyl CoA: NADH+H+ → 3 ATP
• 1 G → 2 pyruvate : 2(NADH+H+) → 6 or
8ATP
1mol G： 36 or 38mol ATP
（12＋3 ）×2 ＋ 6（ 8 ）＝36（ 38 ）
3. The regulation of aerobic
oxidation
• The Key Enzymes of aerobic oxidation
The Key Enzymes of glycolysis
Pyruvate Dehydrogenase Complex
Citrate synthase
Isocitrate dehydrogenase (rate-limiting )
-Ketoglutarate dehydrogenase
(1) Pyruvate dehydrogenase complex
allosteric activators:
AMP, CoA,
NAD+,Ca2+
allosteric inhibitors:
ATP, acetyl CoA,
NADH, FA
Pyruvate dehydrogenase
(active form)
Pi
ATP
pyruvate dehydrogenase
phosphatase
H2O
2+
Ca ,insulin
pyruvate dehydrogenase
kinase
ADP
pyruvate dehydrogenase P
(inactive form)
acetyl CoA,
NADH
ADP,
NAD+
(2) Citrate synthase
• Allosteric activator: ADP
• Allosteric inhibitor: NADH, succinyl CoA,
citrate, ATP
(3) Isocitrate dehydrogenase
• Allosteric activator: ADP, Ca2+
• Allosteric inhibitor: ATP
(4) -Ketoglutarate dehydrogenase
• Similar with Pyruvate dehydrogenase
complex
Oxidative phosphorylation→TCAC↑
• ATP/ADP↑
inhibit
TCAC,
Oxidative phosphorylation ↓
• ATP/ADP↓，promote TCAC，
Oxidative phosphorylation ↑
4. Pasteur Effect
• Under aerobic conditions, glycolysis
is inhibited and this inhibitory effect of
oxygen on glycolysis is known as
Pasteur effect.
• The key point is NADH ：
NADH
mitochondria
Pyr
TCAC
CO2＋H2O
Pyr can’t produce to lactate.
§4 Pentose Phosphate
Pathway
1. The procedure of pentose
phosphate pathway/shunt
 In cytosol
1) Oxidative Phase
NADP+
NADPH+H+
H2O
6-phosphogluco6-Phosphogluconate
G-6-P
G-6-P
nolactone
6-Phospho
dehydrogenase
NADP+
gluconolactonase
6-phosphogluconate
dehydrogenase
Ribose 5-P
Isomerase
Xylulose 5-P
NADPH+H+
CO2
Ribulose 5-P
Epimerase
2) Non-Oxidative Phase
Ribose 5-p
Fructose 6-p
Glycolysis
Fructose 6-p
Xylulose 5-p
Xylulose 5-p
Glyceraldehyde 3-p
• Transketolase: requires TPP
• Transaldolase
The net reation:
3G-6-P + 6NADP+ →
++
2F-6-P
+
GAP
+
6NADPH
+
H
3CO
2
2. Regulation of pentose phosphate
pathway
 Glucose-6-phosphate Dehydrogenase is the
rate-limiting enzyme.
NADPH/NADP+↑, inhibit;
NADPH/NADP+↓, activate.
3. Significance of pentose
Phosphate pathway
1) To supply ribose 5-phosphate for biosynthesis of nucleic acid;
2) To supply NADPH as H-donor in
metabolism;
 NADPH is very important “reducing
power” for the synthesis of fatty acids
and cholesterol, and amino acids, etc.
 NADPH is the coenzyme of glutathione
reductase to keep the normal level of
reduced glutathione;
H2O2
2GSH
NADP+
glutathione reductase
2H2O
G-S-S-G
+
NADPH + H
So, NADPH, glutathione and glutathione
reductase together will preserved the integrity
of RBC membrane.
Deficiency of glucose 6-phosphate
dehydrogenase results in hemolytic
anemia.
 NADPH serves as the coenzyme of
mixed function oxidases (monooxygenases). In liver this enzyme
participates in biotransformation.
§5 Glycogen synthesis and
catabolism
Glycogen is a polymer of glucose
residues linked by
 (1→4) glycosidic bonds, mainly
 (1→6) glycosidic bonds, at branch
points.
1. Glycogen synthesis (Glycogenesis)
• The process of glycogenesis occurs
in cytosol of liver and skeletal muscle
mainly.
ATP ADP
G
G-6-P
HK or GK
UDP
Gn+1
G-1-P
UDPG
glycogen
UDPG
synthase
pyrophosphorylase
UTP
PPi
Gn
• UDPG: G active pattern, G active donor.
• In glycogen anabolism, 1 G consumes 2~P.
• Glycogen synthase: key E.
O
CH2OH
HN
O
H
H
OH
H
O
H
O
OH
H
OH
P
O
O
O
O
P
O
CH2
O
O
H
H
OH
H
OH
H
UDPG
N
Branching enzyme
2. Glycogen catabolism (glycogenolysis)
Pi
Gn
Gn-1
H2O
G-1-P
Phosphorylase
Phosphorylase磷酸化酶:
G-6-P
Pi
G-6-Pase
G
key E;
The end products: 85% of G-1-P and 15%
of free G;
There is no activity of glucose 6phosphatase (G-6-Pase) in skeletal
muscle.
Debranching enzyme:
glucan葡聚糖 transferase
-1,6-glucosidase葡糖苷酶
(1→6) linkage
Nonreducing ends
Glycogen
phosphorylase
Transferase activity of
debranching enzyme
(1→6) glucosidase activity of
debranching enzyme
Glucos
e
3. Regulation of glycogenesis糖原生成 and
glycogenolysis糖原分解
1) Allosteric regulation
In liver:
G
phosphorylase
glycogenolysis
In muscle:
AMP
Ca2+
phosphorylase-b
ATP
G-6-P
phosphorylase-a
glycogenolysis
2) Covalent modification
Glucagon
epinephrine
cAMP
receptor
PKA
G protein
Adenylyl
cyclase
Phosphorylase
Glycogen synthase
glycogenolysis
glycogenesis
Blood sugar
glucagon, epinephrine
active
adenylate cyclase
inactive
adenylate cyclase
cAMP
phosphorylase b
kinase
ATP
ATP
inactive
PKA
ATP
active
PKA
glycogen
synthase
(active)
glycogen
synthase
(inactive)
Pi
H2O
ATP
H2O
phosphorylase b
kinase
ATP
P
inhibitor-1
(inactive)
P
ADP
ADP
Pi
ADP
P
phosphorylase b phosphorylase a
Pi
protein
phosphatase-1
inhibitor-1
(active)
P
H2O
quiz
1，线粒体外NADH经α-磷酸甘油穿梭作用，进入线粒体内实
现氧化磷酸化，其p/o值为
A、0
D、3
2，下列化合物中除(
A、CoQ
NAD+
B、1
C、2
)外都是呼吸链的组成成分。
B、Cytb
C、CoA
D、
3，厌氧条件下，下列哪种化合物会在哺乳动物肌肉组织中
积累？
A、丙酮酸
CO2
B、乙醇
C、乳酸
4，下列化合物中哪一种是琥珀酸脱氢酶的辅酶？（
A、生物素
B、FAD
C、NADP+
D、
）
D、NAD+
5，下列不属于高能化合物的是：
A，1,3－二磷酸甘油酸
C，磷酸烯醇式丙酮酸
E，琥珀酰辅酶A
B，磷酸肌酸
D，6－磷酸葡萄糖
6，胞液中一分子乳酸彻底氧化后产生多少分子ATP？
A，11或12
C，15或16，
B，13或14
D，17或18
7，对二硝基苯酚的描述正确的是
A ，呼吸链阻断剂
的H+梯度
C， 抑制还原当量的转移
B，可破坏线粒体内外
D，可抑制ATP合成酶的活性
8，在TCA（三羧酸循环）中，下列哪一个阶段发生了底物水
平磷酸化？
A，柠檬酸→α－酮戊二酸
C，琥珀酸→延胡索酸
B，α－酮戊二酸→琥珀酸
D，延胡索酸→苹果酸
§6 Gluconeogenesis
糖异生作用
• Concept:
The process of transformation of noncarbohydrates to glucose or glycogen
Materials:
lactate乳酸, glycerol甘油, pyruvate丙酮酸 and
glucogenic amino acid生糖氨基酸
• Site: mainly liver, kidney.
Daily consumption of glucose：
brain
120g
Red blood cell
40g
Resting muscle
40g
Total
200g
Daily available glucose: 150g (stored in liver as
glycogen)，only last for 12h。
在机体内糖的供应不足时，利用非糖物质合成糖
以维持血糖恒定就显得特别重要。
Gluconeogenesis Pathway 糖异生途径
• essentially a reversal of glycolysis（糖酵解）
• but three energy barriers obstructing a
simple reversal of glycolysis.
Gluconeogenesis and glycolysis
NAD+ ⑤磷酸丙糖异构酶
2
⑥3-磷酸甘油醛脱氢酶
ΔG= -0.6kcal/mol
磷酸烯醇式丙酮酸
⑥氧化磷酸化
1.3-二磷酸甘油酸
ΔG= -0.4kcal/mol
ADP
⑦产能 1
⑦磷酸甘油酸激酶
ATP
丙酮酸→
(可逆)
NADH ＋ H
2
克服第1步不可逆反应
磷酸二羟丙酮 ⑤异构
3-磷酸甘油醛
(可逆)
提问：如何进行？
ΔG= +0.3kcal/mol
(可逆)
3-磷酸甘油酸
⑧异构
⑨脱水
ΔG= +0.2kcal/mol ΔG=-0.8kcal/mol
2
⑧磷酸甘油酸变位酶 (可逆)
H20
2-磷酸甘油酸
2
⑨烯醇化酶
（可逆）
磷酸
ADP
烯醇式丙酮酸
ATP
2 丙酮酸
⑩丙酮酸激酶 ⑩产能 2
ΔG= -4.0kcal/mol
(不可逆)
答案：采用
不同的酶,提
供更多的活
化能量迂回
绕过。
carboxylation of Pyruvate
GDP
CO 2
COO
-
CH O ~ P
PEP carboxykinase
GTP
COO
£¨ 1/3Mt.
. 2/3cytosal£©
-
CH2
PEP
ADP
Pyr kinase
ATP
ADP+Pi
ATP
CO
COO
2
C O
Biotin
C O
CH2
Pyr carboxylase
CH3
COOH
£¨ Mt.£©
pyruvate
oxaloacetic acid
pyruvate carboxylase
N subject to
carboxylation
O
C
HN
NH
lysine
residue
CH CH
H2C
CH
S
(CH2)4
O
O
C
biotin
Biotin as coenzyme
NH
C
(CH2)4 CH
NH
O
O
O
-O
C
C
C
C
丙酮酸
O
CH3
pyruvate
O
N
H2C
(CH2)4
C
NH
R
羧
化
生
物
素
O
C
C
O
CH2
HN
NH
O
oxaloacetate
biotin
CH CH
H2C
C
O
O
CH
S
C
草酰乙酸
carboxybiotin
CH CH
O
O
NH
CH
S
(CH2)4
O
C
NH R
生
物
素
Pyruvate Carboxylase
PEP Carboxykinase
O
O
O
O
C
ATP ADP + Pi
C
C
C
O
CH3
O
GTP GDP
CH2
HCO3
C
O
O
O
C
CO2
O
pyruvate
oxaloacetate
丙酮酸
草酰乙酸
C
OPO32
CH2
PEP
磷酸烯醇式丙酮酸
葡萄糖
ATP
①己糖激酶
糖原（淀粉）
①活化
ΔG= -7.5kcal/mol
磷酸化酶
(不可逆)
磷酸
ADP
磷酸葡萄糖变位酶
6-磷酸葡萄糖
②磷酸葡萄糖
异构酶
1-磷酸葡萄糖
②异构
ΔG= -0.6kcal/mol
(可逆)
6-磷酸果糖
ATP
③磷酸果糖激酶
ADP
1．6—二磷酸果糖
④醛缩酶
3-磷酸甘油醛
③二次活化
ΔG= -5.0kcal/mol
(不可逆)
④裂解
ΔG= -0.3kcal/mol
磷酸二羟丙酮 (可逆)
• 磷酸烯醇式
丙酮酸逆行
至1，6-二磷
酸果糖
• 第2步
提问：如何进行？
OCH2 O CH
P•答案：在
P酶作
2O
水解
HO
用下水解。
1，6-二磷
酸果糖
OH
•第3步
水解酶催化
P OCH2 O CH2OH
HO
6-磷酸果糖
磷酸烯醇式丙酮酸
OH
Two Glycolysis irreversible reactions are
bypassed by simple hydrolysis reactions:
Fructose-1,6-bisphosphatase
6 CH OPO 2
2
3
1 CH2OPO32
O
5
H
H
4
OH
HO
2
3 OH
H
fructose-1,6-bisphosphate
H2O
CH2OPO32
O
H
CH2OH
+ Pi
HO
H
OH
OH
H
fructose-6-phosphate
Glucose-6-phosphatase
6 CH OPO 2
2
3
5
O
H
4
OH
H
OH
3
H
H
2
CH2OH
1
OH
OH
glucose-6-phosphate
O
H
H
H2O
H
OH
H
+ Pi
H
OH
OH
H
glucose
OH
glyceraldehyde-3-phosphate
NAD+ + Pi
Glyceraldehyde-3-phosphate
Dehydrogenase
NADH + H+
Summary of
Gluconeogenesis
Pathway:
糖异生途径总结.
1,3-bisphosphoglycerate
ADP
Phosphoglycerate Kinase
ATP
3-phosphoglycerate
Phosphoglycerate Mutase
2-phosphoglycerate
Enolase
H2O
phosphoenolpyruvate
CO2 + GDP
PEP Carboxykinase
GTP
oxaloacetate
Pi + ADP
HCO3 + ATP
pyruvate
Pyruvate Carboxylase
Gluconeogenesis
glucose
Pi
Gluconeogenesis
Glucose-6-phosphatase
H2O
glucose-6-phosphate
Phosphoglucose Isomerase
fructose-6-phosphate
Pi
Fructose-1,6-bisphosphatase
H2O
fructose-1,6-bisphosphate
Aldolase
glyceraldehyde-3-phosphate + dihydroxyacetone-phosphate
Triosephosphate
Isomerase
(continued)
glucose
glycogen
G-6-P
G-1-P
gluconeogenesis
CYTOSOL
MITOCHONDRIA
F-6-P
NAD+
glyceraldehyde 3-P
glutamate
glutamate
¦Á-ketoglutarate
NADH+H+
DHAP
malic acid
malic acid
F-1,6BP
OAA
Asp
¦Á-ketoglutarate
NADH+H+
Asp
1.3-bisphospho2/3
glycerate
CO2
ADP
GDP
ATP
glycerate 3-P
phosphoenol
pyruvate
ADP
glycerate 2-P
PK
ATP
NAD+ NADH+H+
lactate
pyruvate
OAA
GTP
GTP
glycerol
NAD+
ADP
CO2
GDP
1/3
phosphoenol
pyruvate
ATP
CO2
pyruvate
Key enzymes of gluconeogenesis
PEP carboxykinase
Pyr carboxylase
Fructose-bisphosphatase
Glucose-6-phosphatase
gluconeogenesis:
F-6-P
Pi
F-2,6-BP
PFK-1
FBPase-1
AMP
H2O
ATP
F-1,6-BP
glycolysis
ADP
F-2,6-BP
glucagon
PEP
ADP
F-1,6-BP
glucagon
Ala in liver
insulin
OAA
ATP
Pyr
acetyl CoA
What Materials can be Transformed
to Glucose by Gluconeogenesis?
1），All
those that can be transformed to pyruvate
and any intermediate in TCAC, via oxaloacetate.
– Glucogenic AA生糖氨基酸(mainly precursor when
starving)
– 反刍动物转化纤维素形成的有机酸
gluconeogenesis
fermentation
cellulose
有机酸
glucose
2），glycerol
3），lactate
肌肉剧烈运动后产生的大量
乳酸，经血液运输到肝脏，氧化成丙酮酸进入
糖异生途径变成葡萄糖，再进入血液运输到肌
肉中，构成Cori 循环，
Lactic acid (Cori) cycle
• Lactate, formed by the oxidation of glucose in
skeletal muscle and by blood, is transported to the
liver where it re-forms glucose, which again
becomes available via the circulation for oxidation
in the tissues. This process is known as the lactic
acid cycle or Cori cycle.
• prevent acidosis；reused lactate
Lactic acid cycle
glucose
glucose
gluconeogenesis
glucose
glycolytic
pathway
pyruvate
pyruvate
NADH+H+
NAD+
NAD+
NADH+H+
lactate
liver
lactate
lactate
blood
muscle
Gluconeogenesis is energy consuming
1．pyruvate ＋ ATP ＋ HCO3－
2．草酰乙酸 ＋GTP
3．3－P－甘油酸 ＋ ATP
oxaloacetate＋ ADP ＋Pi ＋ H＋
PEP ＋ CO2 ＋ GDP
1，3－二磷酸甘油酸 ＋ ADP ＋ Pi
Net ATP consumption: 4ATP
2 pyruvates
1 glucose
glucose，use 6 ATP
2 pyruvate, net productioin 2 ATP
So, what’s the significance of lactic acid cycle?
花费能量为代价换取肌肉中能量的产生
3. Significance of gluconeogenesis
(1) Replenishment(补充) of Glucose by
Gluconeogenesis and Maintaining Normal
Blood Sugar Level.
(2) Replenishment of Liver Glycogen.
(3) Regulation of Acid-base Balance.
(4) Beneficial for prey(被捕食者) and predator（捕食者）
In survival competition
§6 Blood Sugar and
Its Regulation
1. The source and fate of blood sugar
origin (income)
fate (outcome)
CO2 + H2O + energy
dietary supply
liver glycogen
non-carbohydrate
(gluconeogenesis)
other saccharides
blood sugar
glycogen
3.89¡« 6.11mmol/L
other saccharides
non-carbohydrates
(lipids and some
amino acids)
>8.89¡« 10.00mmol/L
(threshold of kidney)
urine glucose
Blood sugar level must be maintained
within a limited range to ensure the
supply of glucose to brain.
The blood glucose concentration is
3.89～6.11mmol/L normally.
2.Hormones Regulating
blood sugar level
1）insulin： decreasing (unique)
2）glucagon：increasing
3）glucocorticoid（糖皮质激素）:increasing
4）adrenaline（肾上腺素）：increasing
3. Abnormal Blood Sugar Level
• Hyperglycemia: > 7.22～7.78 mmol/L
• The renalthreshold for glucose (肾糖阈）:
8.89～10.00mmol/L
• Hypoglycemia: < 3.33～3.89mmol/L
Summary of
carbohydrate
metabolism
1st stage
(cytosol)
2nd stage
(Mt.)
3rd stage
(Mt.)
Exercise
1,从乳酸进行糖异生不需要（）活性
A 醛缩酶
B 磷酸果糖激酶 C 3-磷酸甘油脱氢酶
D 乳酸脱氢酶
2，下列化合物对人糖异生中葡萄糖的净生成没有作用的是（）
A 丙酸盐 B甘油 C 乙酰辅酶A
D 乳酸 E 丙氨酸
3，糖异生的第一步由（）催化
A 己糖激酶 B 丙酮酸羧化酶
C PEP羧激酶
D 丙酮酸激酶
4，乳酸异生为糖的过程发生在（）
A 细胞质 B 线粒体 C 细胞核 D 核糖体
5，高AMP水平对糖酵解和糖异生的影响是什么？它是通过什么原理实现的？