Chapter 8~9
Carbohydrate Metabolism
牛永东
【目的与要求】
1.糖的消化、吸收;
2.糖酵解反应过程、调节;
3.有氧氧化(三羧酸循环)反应过程、调节;
4.磷酸戊糖途径反应的两个阶段、调节;
5.糖原合成与分解;
6.糖异生(途径);
7.巴斯德效应、乳酸循环、Cori cycle;
8.血糖的来源和去路及其调节……
各代谢的细胞定位、过程、关键酶、调节及意义……
学习方法
• 因素一：未进入定量阶段，尚处于定性阶段
• 因素二：自然界很少存在永恒/绝对，几乎所有结论
都可能或将可能被一些例外打破（生物多样性）
• 要求：课前预习（看小说）数遍，课堂专心听讲（省时省
力），课后复习（重要），择重记忆（概念--记忆为主，
记忆基础上理解）
• 如何学习好？
Tips：关键要学好“糖代谢”
？
outline
• Background
• Glycolysis (Anaerobic Degradation)
• Aerobic oxidation of glucose
• The Pentose Phosphate Pathway
• Glycogen Formation and Degradation
• Gluconeogenesis
Background
* Breakdown (catabolism):
A Glycogen – Glucose
A TG – Fatty Acids + Glycerol
A Protein – Amino Acids
ANABOLISM
A Requires Energy
CATABOLISM
• Metabolism (Greek for change) :
all the chemical and physical processes that take place in the body
* Synthesis (anabolism):
Macromolecules
A Glucose – Glycogen
A FA+ Glycerol – TG
A Amino Acids – Protein
Small
molecules
A Energy is released
What are Carbohydrates?
• Carbohydrates are aldehyde or ketone compounds with
multiple hydroxyl groups
• Empirical formula = (CH2O)n, literally a “carbon
hydrate”
• CH2O make up 3% of the body’s organic matter
Functions of CH2O
• Energy Source(66.8 kJ/1g carbohydrate)
• Structural elements
• Component of nucleic acids
• Conversion to lipids and non-essential amino acids
• …….
Categories of Carbohydrates
 Monosaccharides (Single sugar units): the smallest
carbohydrates ,serve as fuel and carbon sources
 Disaccharides (formed from 2 monosaccharides joined by a
glycoside linkage)
 Polysaccharides: many monosaccharide units (starch, cellulose)
Monosaccharides
• Glucose (C6H12O6) 葡萄糖
Glucose (C6H12O6)
-found in fruits, vegetables, honey
-“blood sugar”
-used for energy
• Fructose
果糖
- Found in fruits, honey, corn syrup H
HOH 2 C
-“fruit sugar”
HO
• Galactose 半乳糖
- Found as part of lactose in milk
O
H
HO
H
H
椅式
OH
OH H
环状
Disaccharides
 Sucrose = glucose + fructose (brown sugar;25% of sugar intake) 蔗糖
 Maltose = glucose + glucose (honey) 麦芽糖
Natural Sweetness
 Lactose = glucose + galactose (milk sugar; least sweet) 乳糖
果糖>蔗糖>葡萄糖>麦芽糖>半乳糖
Sucrose
Maltose
Polysaccharides
6CH 2 OH
蓝色:
α-1,6-糖苷键
红色:
α-1,4-糖苷键
Glucose
O
4
OH
H
H
HO
O
O
O
CH2OH
O
CH2OH
CH2
O
O
O
OH
CH2OH
O
O
-[1,4] linkages
-[1-6] linkage
CH2OH
O
O
1
OH
H
CH2OH
O
starch
O H
H
Section 1 Digestion of carbohydrates
Starch
Pancreatic amylase
麦芽三糖
Salivary amylase
麦芽糖
α-糊精
-葡萄糖苷酶
G
葡萄糖
-糊精酶
Starch
Mouth
α-mylase
Glycogen
Brush Border
of the Mucosal
Epithelium
1
glucose
2
fructose
stomach
maltose
sucrose
3
galactose
galactose
Monosaccharides
limited breakdown
of starch and
glycogen occurs
glucose
fructose
no significant
digestive
enzymes
present
Responsible for
most of
carbohydrate
digestion
BLOOD
lactose
部位：*口腔
*小肠
Na+ dependent glucose Absorption and transporter, GLT
facilitated diffusion
GLT
GLT
+
Na dependent
co-transport
Intestinal Epithelial cell
Family of glucose transporters
Name
Tissue location
Km
GLUT1
GLUT2
All mammalian tissues
1mmol/L
Liver and pancreatic
15~20mmol/L
 cells
GLUT3
GLUT4
All mammalian tissues
Muscle and fat cells
GLUT5
Small intestine
1mmol/L
5mmol/L
－
Comments
Basal glucose uptake
In the pancreas,plays a role
in regulation of insulin
In the liver, removes excess
glucose from the blood
Basal glucose uptake
Amount in muscle plasma
membrane increases with
endurance training
Primarily a fructose transporter
Not digested: Dietary Fiber
 Water insoluble fibers
- Cellulose, hemicellulose , pectins 果胶……
 Water soluble fiber
- beans, rice, carrots, fruits……
- Obesity, diabetes, cancer……
 Recommended intake of fiber
 20-35 g/day; insoluble:soluble = 3:1
Overview of carbohydrate metabolism
Glycogen
Glycogenesis UDPG
4
G1P
Glycogenolysis
Pi
5
G6P
glucose
Pi
F6P
6-phosphogluconate
Pentose phosphate pathway
3
non-carbohydrates
trioses phosphate
Anaerobic degradation
(glycolysis)
lac tate
1
Pyruvate
G luc o ne o g e ne sis
acetyl CoA
Tricarboxylic acid cycle
CO2 +H 2O+ energy
6
Aerobic oxidation
2
Section 2 Glycolysis (Anaerobic Degradation)
• “Glycolysis” is derived from Greek words glycos (sugar,
sweet) and lysis (dissolution)
• The glycolytic pathway (Glucose to pyruvate) was
elucidated by 1940, largely through the pioneering
contributions of Gustav Embden. so glycolysis is also
known as the Embden-Meyerhof pathway
Glycolysis
糖酵解
• For glycolysis, the overall goal is to break the glucose
molecule into smaller, more oxidized pieces
• 11 steps metabolic pathway to convert 6 carbon
glucose into 2 molecules of 3 carbon lactate 乳酸and
two molecules ATP (and NADH * )
• Occurs in cytoplasm
* glycolysis has two stages:
1. glycolytic pathway (Glucose to pyruvate) ,including two phases
2.Fermentation phase 发酵 (pyruvate to lactate)
• Anaerobic
– Does not REQUIRE oxygen
– Occurs whether oxygen is available or not
** glycolytic pathway = breakdown of glucose
to yield energy and pyruvate
CH2OH
O
or
break
C3break
C4 C3-C4
bond
bond
D-glucose
breakage of C3-C4 bond
glycolytic pathway has two phases
A. Energy investment phase (Reactions, 1-5)
Glucose(6C) is first phophorylated (thus activated) and
then cleaved to produce two glyceraldehyde-3phosphate(3C) intermediates. 2 ATPs are invested (the
preparatory phase)
B. Energy payoff phase (Reactions 6-10)
two glyceraldehyde 3-phosphate intermediates are oxidized,
generating to two pyruvate plus four ATP molecules
Energy investment phase
O
-P-O
OH
isomerase
glucose
O
CHO
-P-O
CH2 OH
H-C-OH
C=O OH
HO-C-H
H-C-OH
H-C-OH O
CH2 O H-P-O
OH
Step 1. Hexokinase (1 ATP utilization)
Step 2. Phosphoglucose Isomerase (PGI)
Step 3. Phosphofructokinase -1 (PFK-1) (2 ATP utilization)
energy investment phase
dihydroxyacetone phosphate
O
CHOOH
CH
2 -P-O
H-C-OH
C=O OH
HO-C-H
H-C-OH
H-C-OH O
C H2 OH-P-O
OH
4. Aldolase
O
CH2O -P-O
C=O OH
HO-C-H
H
+
H-C-OH
H-C-OH O
CH2O -P-O
OH
CH2OPO3=
C=O
CH2OH
DHAP
HC=O
H-C-OH
CH2OPO3=
Glyceraldehyde 3-PO4
energy investment phase
dihydroxyacetone phosphate
Glyceraldehyde 3-PO4
TPI
isomerase
The isomerization of an aldose to a ketose
5. Triose Phosphate Isomerase (TIM or TPI )
energy investment phase
Glucose
Hexokinase
ATP
ADP
Glucose 6-phosphate
Phosphogluco- isomerase
Uses 2 ATP
Fructose 6-phosphate
Phosphofructokinase
ATP
ADP
Fructose 1.6-bisphosphate
Aldolase
Dihydroxyacetone
phosphate
Triose phosphate isomerase
Glyceraldehyde
3-phosphate
Energy payoff phase
(Reactions, 6-10)
O
C ~OPO3
PO4
CHO
H-C-OH
CH2OPO3
NAD+
H-C-OH
NADH + H+
Glyceraldehyde-3-PO4
dehydrogenase
CH2OPO3
COO
ADP
ATP
H-C-OH
Phosphoglycerate
kinase
Where ?
CH2OPO3
Energy payoff phase
COO
H-C-OH
Low energy
CH2OPO3
3-PGA
COO
H-C-OPO3
COO
-H2O
High energy
C~ OPO3
CH2OH
CH2
2-PGA
PEP
ADP
COO
C=O
ATP CH3
Pyruvate
Glyceraldehyde 3-phosphate
Glyceraldehyde
NAD+ + Pi
3-phosphate
dehydrogenase
NADH + H+
1,3-Bisphosphoglycerate
ADP
Phosphoglycerate kinase
ATP
3-Phosphoglycerate
Oxidation
ATP generation
Phosphoglyceromutase
2-Phosphoglycerate
Enolase
HO
Phosphoenolpyruvate
2
ADP
ATP
Pyruvate kinase
Pyruvate
ATP generation
energy payoff phase
Energy investment phase
Energy payoff phase
Summary of
Energy Relationships for glycolytic pathway
* Input = 2 ATP
1. glucose + ATP  glucose-6-P
2. fructose-6-P + ATP  fructose 1,6 bisphosphate
* Output = 4 ATP + 2 NADH
1. 2 glyceraldehyde-3-P + 2 Pi + 2 NAD+
2 (1,3 bisphosphoglycerate) + 2 NADH
2. 2 (1,3 bisphosphoglycerate) + 2 ADP
2 (3-P-glycerate) + 2 ATP
3. 2 PEP + 2 ADP  2 pyruvate + 2 ATP
**
Net =2 ATP and 2 NADH
Fate of Pyruvate
• Two anerobic pathways: (Low O2 )
- to lactate via lactate dehydrogenase in muscle
- to ethanol (fermentation) via ethanol dehydrogenase
• Aerobic pathway – through citric acid cycle and
respiration; Enough O2,this pathway yields far more
energy
NADH + O2  NAD+ + energy
Pyruvate + O2  3CO2 + energy
Oxygen availability
determines fate of Pyruvate
Pyruvate
Alcohol
Fermentation
Anaerobic
Glycolysis
Aerobic Glycolysis
The anaerobic fate of Pyruvate ( Reaction 11 of glycolysis )
From?
• Hydrogen at C4 of
NADH is transferred
to the pyruvate
uses up all the NADH
(reducing equivalents)
produced in glycolysis
Energy Yield From Glycolysis
Overall process of anaerobic glycolysis in muscle can be represented:
The lactate, the end product, is exported from the muscle cell
and carried by the blood to the liver, where it is reconverted to
glucose
• Glucose ---------6 CO2
-2840 kJ/mol
• 2 ATPs produced 61 kJ/mol glucose
• Energy yield = 61/2840 = 2%
in all: high investment, low output
Summary of Glycolysis
6c互变
a. 11 steps ; Location: cytosol
b. Original material: glucose (C6H12O6)
6c变3c
c. End product: lactate
醛变酸 3c-3c
- Twice substrate level phosphorylations
酸变酸 3c-3c
- Net of 2 ATP
d. Key enzymes: Hexokinase (HK) …energy investment phase
Phosphofructokinase 1 (PFK-1) …energy investment phase
Pyruvate kinase (PK) …energy payoff phase
e. Once dehydrogenation: oxidation
Once hydrogenation: reduction
f. No oxygen is required
The regulation of glycolysis

Glucagon
Glucose
ATP
Adenylate
cyclase
cAMP

ATP
AMP
Citrate

－
Hormone regulation
Covalent regulation
Allosteric regulation
ADP
PFK-2 FBP-2
active inactive
Glucose 6-phosphate
ATP
F-6-P
ADP
glycolysis
F-2,6-BP
PKA Phosphoprotein
Phosphatase
ATP
P
P
Pi
PFK-2 FBP-2
active
inactive
－
Lactate
PFK-1

ADP 

F-1,6-BP

－
AMP
Citrate
Pi
3. The significance of glycolysis
• Glycolysis is the emergency energy-yielding
pathway, such as play ball, climb mountain.…..
• Glycolysis is the major way to produce ATP in
some tissues, even though the oxygen supply is
sufficient, such as RBC, retina, testis, skin……
Section 3 Aerobic oxidation of glucose
• The process of oxidation completely from glucose to
CO2 and H2O is named aerobic oxidation
• This process is the major process to provide energy for
most tissues
** 3 phases of Glucose Aerobic oxidation
1. Oxidation from glucose to pyruvate in cytosol
(6C to 3C)
2. Oxidation from pyruvate to acetyl CoA in mitochondria (3C to 2C)
3. Tricarboxylic acid cycle and oxidative phosphorylation (2C to 1C)
O2
O2
H 2O
O2
Acetyl CoA
Glucose
H+ +e
G-6-P
Pyruvate
TCA cycle
Pyruvate
cytosol
mitochondria
CO2
2. Oxidation from pyruvate to acetyl CoA
(3C to 2C)
O
O
C
C
C H3
O-
Pyruvate DH complex
O
S
C
CoASH
NAD+
C H3
NADH
C oA +
CO 2
Acetyl-CoA: a common two-carbon unit
Pyruvate+NAD++HSCoA
Acetyl CoA+NADH+H++CO2
Pyruvate dehydrogenase complex
E1. pyruvate dehydrogenase
（丙酮酸脱氢酶）
E2. dihydrolipoyl transacetylase
（二氢硫辛酰胺转乙酰酶）
E3. dihydrolipoyl dehydrogenase
（二氢硫辛酰胺脱氢酶）
Pyruvate dehydrogenase complex
3. Two stages
of the 3rd phase of Glucose Aerobic oxidation
• Stage I The acetyl-CoA is completely oxidized into
CO2, with electrons collected by NAD and FAD via a
cyclic pathway (tricarboxylic acid cycle)
• Stage II Electrons of NADH and FADH2 are
transferred to O2 via a series carriers, producing H2O
and a H+ gradient, which will promote ATP
formation （oxidative phosphorylation）
(NEXT CHAPTER)
Tricarboxylic acid cycle (2C to 1C)
• Citric Acid Cycle or Krebs cycle
• Occurs in mitochondrial matrix
• Is the biochemical hub of the cell, oxidizing carbon fuels,
usually in the form of acetyl CoA, interconversion of
carbohydrates, lipids, and some amino acids, as well as
serving as a source of precursors for biosynthesis
• For the citric acid cycle, the goal is to use the oxidative
power of O2 to derive as much energy as possible from
the products of glycolysis
Substrates required:
Oxaloacetic Acid GDP 3NAD+
FAD two-carbon units (Acetyl-CoA)
Intermediate Reactants: Citric Acid
Output:
Oxaloacetic Acid GTP
3 NADH FADH2 2CO2
(4 high-energy electrons)
C2
C6
C4
NADH+H+
FADH2
GTP
Each Acetyl-CoA yields
2 CO2, 3 NADH + H+,
1 FADH2, 1 GTP
Tricarboxylic acid cycle
NADH+H+
CO2
C5
C4
NADH+H+
CO2
Stage I Tricarboxylic acid cycle
O
2C
S
C
C
HO
O
O-
C3
CoASH
C2
C
C H2 O -
C
C H2
C
O
O-
C H2 O
Citrate synthase
＋
4C
-O
C oA
C H3
O
O
-O
Oxaloacetic Acid
C1
O
Citrate
6C
O
O-
C
C1
6C
Aconitase
C
O
H 2C
C
C
C2
C H2 O -O
O
C3
C H2 O
HO
O-
O
H
C
C
OO
-O
cis-aconitate intermediate
6C
O
O-
O
C
C H2 O
H
HO
C
C
O-
C
C
O
-O
6C
Isocitrate
OC
CO2
C H2
Isocitrate DH
+
C H2
NAD
O
NADH
C
C
O
-O
a-ketoglutarate
5C
O
OO
C
C H2
a-ketoglutarate DH
C H2
O
NAD+,
C
C
-O
O
5C
a-ketoglutarate
OC
C H2
CO2
+
C H2
CoASH
O
NADH
C
S C oA
4C
Succinyl CoA
O
O-
O
C
C H2
SuccinylCoA synthetase
C H2
O
C
S C oA
4C
Succinyl CoA
OC
C H2
GDP, Pi
C H2
O
CoASH
C
+
GTP
O4C
O
O
OC
C H2
O
O-
C
C H2
C
C
H
(FAD)
C
O
C
(FADH2)
+
H
O-
O-
4C
fumarate
4C
O
C
H
O-
C
C
O
C
HO
H
Ofumarate
O
4C
C
O-
C
H
CH2
H2 O
-O
C
O
malate
4C
O
HO
C
C
O-
O
H
CH2
-O
C
O
C
malate DH
CH2
NAD+
-O
O
malate
C
C
O+
O
Oxaloacetic Acid
4C
NADH
4C
O
C H3 C
C
O
C O O H
C H
2
C O O H
+
NADH+ H
~S C o A C o A S H
C H2 C O O H
C H2 C O O H
HO C C O O H
citrate synthase
C
C H2 C O O H
C O O H
C H
C O O H
NAD+
H O CH
CO O H
C H2 C O O H
Tricarboxylic acid cycle
HC C O O H
HO C H
HC C O O H
H OO C C
H
FAD2 H
C H2 C O O
+H
+
NADH+
NAD
H
GTP
O
GDP+Pi
C
~S C oA
+
+
NADH+ H
C O2
C H2 C O O H
C H2
C H2
CoASH
C O O H
N AD
isocitrate dehydrogenase
FAD
C H2 C O O H
C H2 C O O H
C H2 C O O H
CoASH
C O2
O
C
C O O H
- ketoglutarate dehydrogenase
Aerobic oxidation of glucose
C6H12O6 + 6O2 + 38 ADP +38 P
6CO2 + 6H2O + 38 ATP
Generation of ATP in aerobic oxidation of glucose
Reactions
Catalyzed by
Glycolytic
pathway
Glyceraldehyde 3-phosphate
dehydrogenase
Methods of
ATP production
formed moles of ATP
Respiratory chain Oxidation of 2 NADH
Phosphoglycerate kinase
Phosphorylation at substrate level
Pyruvate kinase
Phosphorylation at substrate level
consumption of ATP by reactions catalyzed by hexokinase and phosphofructokinase
Production of
acetyl CoA
TCA cycle
6 or 4 /5 or 3
2
2
-2
Pyruvate dehydrogenase
complex
Respiratory chain Oxidation
of 2 NADH
6 or 5
Isocitrate dehydrogenase
Respiratory chain Oxidation of 2 NADH
6 or 5
Alpha-ketoglutarate
Dehydrogenase complex
Respiratory chain Oxidation of 2 NADH
6 or 5
Succinyl CoA synthetase
Phosphorylation at substrate level
2
Succinate dehydrogenase
Respiratory chain Oxidation of 2 FADH2
4 or 3
Malate dehydrogenase
Respiratory chain Oxidation of 2 NADH
6 or 5
Total per mole of glucose under aerobic conditions: 32 or 30(38 or 36) ATPs
Regulation of aerobic oxidation
pyruvate
Regulation of pyruvate dehydrogenase
C2
3 control points
of citric acid cycle :
C4
Iso C6
Krebs Cycle
isocitrate dehydrogenase
C5
C4
citrate synthase
-ketoglutarate dehydrogenase
Regulation of pyruvate dehydrogenase
Inhibited by products,
NADH & Acetyl CoA
Also regulated by covalent modification,
the kinase & phosphatase also regulated
The Alosteric regulation of citric acid cycle
Acetyl CoA
citrate synthase
isocitrate dehydrogenase
- ketoglutarate dehydrogenase
CoA
[1]
Citrate
Oxaloacetate
cis - Aconitate
NADH
Isocitrate
[6]
NAD+
[2]
Malate
NADH, CO2
-Ketoglutarate
[3]
Allosteric inhibitor
Fumarate
FADH2
ADP
allosteric activator
NAD+
[4]
[5]
Succinate
FAD
Succinyl CoA
GDP
GTP
CoA,
NAD+
NADH:
allosteric inhibitor
NADH, CO2
GTP
allosteric inhibitor
* Pastuer effect
• The total amount of glucose consumed by yeast are about 7 times
greater under anaerobic conditions than under aerobic conditions
• This effect is also seen in muscle under anaerobic conditions
• The yield of ATP under anaerobic conditions is 2 per molecule;
but under aerobic conditions the yield is 38 ATP per glucose
• Therefore, glucose flux through the pathway is regulated to
achieve constant ATP levels or decided by the fate of
NADH+H+
•
“Crabtree effect “
Section 4
The Pentose Phosphate Pathway (PPP) **
• The PENTOSE PHOSPHATE pathway ,by carring out oxidation and
decarboxylation of the 6-C sugar glucose-6-P, is basically used for the
synthesis of NADPH and 5-C sugar ribulose-5-P
• It plays only a minor role (compared to GLYCOLYSIS) in degradation for ATP
energy
• Other names:
Pentose phosphate Shunt
Hexose Monophosphate Shunt
Pentose phosphate pathway
• Two stages:
– Oxidative portion (NADPH producing)
– Non-oxidative (carbon recycling/unit transferring)
• Location: cytosol
• Original material: glucose 6-phosphate
• End product: NADPH , pentose phosphate
• Important in adipose tissue, adrenal cortex, liver
(biosynthesis), Important in red blood cells (antioxidant
reasons)
STAGE
I
(Oxidation=NADPH producing and formation of pentose phosphate)
O
COO
CHO
C
C-OH
HO-C
C-OH
C-OH
CH2OP
NADP+
C-OH
C-OH
HO-C
NADPH + H+
G-6-P
dehydrogenase
C-OH
O
C
HO-C
C-OH
Lactonase
C-OH
CH2OP
+ H2O
CH2OP
6-Phosphoglucono-6-PhosphoGlucose-6-PO4
lactone
gluconate
G-6-P dehydrogenase: Rate limiting step, controlled by NADP+ levels
Glucose-6-phosphate Dehydrogenase catalyzes oxidation of the aldehyde
(hemiacetal), at C1 of glucose-6-phosphate, to a carboxylic acid, in ester
linkage (lactone). NADP+ serves as electron acceptor
STAGE
COO-
I
Ribulose-5-PO4 (Ru5P)
Ribose-5-PO4
CH2OH 5C
CHO
CO2
HO-C-H
C=O
C-OH
C-OH NADP+
C-OH
C-OH
Ru5P
C-OH
C-OH
isomerase C-OH
+
NADPH + H
CH2OP
CH2OP
CH2OP
Ru5P
6-phosphogluconate
6C
epimerase
Dehydrogenase
CH2OH
6-Phosphogluconate
C=O
HO- C
C-OH
5C CH2OP 5-p-木酮糖
Xylulose-5-PO4
C-OH
5C
STAGE II ( Non-oxidative=carbon recycling)
CH2OH
5C
5C
3C
CH2OH
C=O
HO- C
C-OH
CH2OP
Xyulose-5-PO4
+
CHO
C-OH
CH2OP
Glyceraldehyde-3-PO4
CHO
C-OH
C-OH
C-OH
CH2OP
酮醇转移酶 2C
Transketolase
Ribose-5-PO4
C=O
HO-C
C-OH
C-OH
C-OH
CH2OP
7-p-景天糖
Sedoheptulose-7-PO4
7C
STAGE II ( Non-oxidative=carbon recycling)
CH2OH
CH2OH
C=O
HO-C
C-OH
C-OH
CH2OP
C=O
CHO
HO-C
C-OH
C-OH
+
CH2OP
3C
C-OH
C-OH
Glyceraldehyde-3-PO4
CH2OP
Sedoheptulose-7-PO4
7C
CHO
C-OH
C-OH
CH2OP
4-p-赤藓糖
Erythrose-4-PO4
Fructose-6-PO4
Transaldolase
醛糖移转酶 3C
4C
6C
STAGE II ( Non-oxidative=carbon recycling)
CHO
C-OH
C-OH
CH2OP
CH2OH
C=O
+
Erythrose-4-PO4
4C
HO- C
C-OH
CH2OP
CH2OH
CHO
C=O
C-OH
+ HO-C
CH2OP
C-OH
C-OH
Glyceraldehyde-3-PO4
CH2OP
Xylulose-5-PO4
3C
5C
Transketolase
Fructose-6-PO4
6C
glycolysis
Pentose phosphate pathway
Oxidative stage
ATP
Glucose
ADP
NADP
NADPH
Glucose 6-P
6-Phosphogluconate
CO2
Ribulose 5-P
Non-oxidative stage
Xylulose 5-P
Glyceraldehyde 3-P
(5C)
( 5C)
Glyceraldehyde 3-P
(3C)
Fructose 6-P
Erythrose 4-P
(4C)
NADP
NADPH
Ribose 5-P
(5 C)
Sedoheptulose 7-P
(7 C)
Fructose 6-P
(6C)
SUMMARY
+
+
+
+
3CO2
+
C5 + C5  C3 + C7
(Transketolase)
C3 + C7  C6 + C4
(Transaldolase)
C5 + C4  C6 + C3
(Transketolase)
C3 + C6+ C6
C5 + C5 + C5
3 C5  2 C6 + C3
(Overall)
3 Glucose-6-PO4 + 6 NADP+ + 3H2O
6 NADPH + 6H+ + 3CO2 + 2 Fructose-6-PO4
3 G 6-P
•Per glucose oxidized, 2 NADPHs are formed
+ Glyceraldehyde-3-PO4
•C7、C4 are strictly intermediates
•Glyceraldehyde-3-PO4 is both an intermediate and final product
•Fructose-6-PO4 is never used as an intermediate, return to the glycolytic pathway
*** The significance of PPP
1. Produce ribose 5-phosphate
needed for DNA and RNA synthesis
2. Generate reducing equivalents NADPH
1) Reducing power for biosynthesis of fatty acids,
cholesterol, folate, and so on
2) Coenzyme of glutathione reductase to keep the
normal level of reduced glutathione
3) NADPH serves as the coenzyme of mixed function
oxidases (mono-oxygenases)
Section 5
Glycogen Biosynthesis and Degradation
Introduction
A constant source of blood glucose is an absolute
requirement for life
- glucose is the preferred energy source for
the brain and for cells with few or no
mitochondria, such as mature erythrocytes
- glucose is an essential energy source in
exercising muscle
What is Glycogen?
CH2OH
O
O
a-1,6-glycosidic linkage））
CH2OH
CH2OH
O
CH2OH
O
CH2OH
CH2O
O
O
Reducing end
a-1,4-glycosidic linkage
1. Glycogen is a highly branched homopolymer of a-glucose (polysaccharide)
2. Approx. every 10 residues there is a branch, linked by an a-1,6-glycosidic
linkage
Glycogen Biosynthesis(Glycogenesis)
• Glycogenesis: the process of storing excess glucose as glycogen (In times
of plenty the body needs to store fuel)
• occurs in the cell cytoplasm of liver, muscle & kidney, when blood
glucose levels are high
• Excess glucose is stored (limited capacity)
– liver and muscle are major glycogen storage sites
• liver glycogen used to regulate blood glucose levels
– brain cells cannot live for > 5 minutes without glucose
• muscle glycogen used to fuel an active muscle
• Glycogenesis involves addition of a-D-glucose residues to the C4 (nonreducing end) of an pre-existing chain
Requirement of formation glycogen
• Glycogenin
• glycogen synthase
• glycogen-branching enzyme
• UDP-glucose pyrophosphorylase
Requirement of Formation glycogen
• Primer
– glycogenin acts as the primer to which the
first glucose residue is attached
– glycogenin also catalyzes attachment of
additional glucose units to form chains of
up to eight units
• Glycogen-branching enzyme
– takes over at this point
– chain cannot extend indefinitely
Requirement of Formation glycogen
• Glycogen Synthase
– exists in an active (dephosphorylated) and inactive (phosphorylated)
form
– relative amount of each form is regulated by cellular level of cAMP
– cAMP is regulated by insulin:glucagon ratio
• High insulin keeps GS in dephosphorylated, active form
• High insulin can also stimulate dephosphorylation of GS
• High glucagon activates cAMP which activates PK which phosphorylates
and inactivates GS
– Glycogen Synthase reaction is primary target of insulin’s
stimulatory effect on glycogenesis
Glycogenesis
2Pi
ATP
glucose
Mg2+
UTP
(uridine
triphosphate)
phospho
glucomutase
ADP
G-6-P
PPi
H2O
G-1-P
glycogen
primer
UDP
UDPG
glycogen
(uridine GLYCOGEN ¦Á -1,4-glycosidic
diphosphate SYNTHASE
bond
glucose)
GK(liver),HK
branching
enzyme
glycogen
¦Á-1,4,¦Á -1,6glycosidic bond
O
O
NH
CH2OH
O
O
O
G-1-P
P
O- + -O
O-
P
O
O-
P
N
O
O
O
O
O-
P
O
O-
UTP
CH 2 O
H
H
H
OH
OH
O
PPi
NH
CH2OH
O
O
O
UDPG pyrophosphorylase
P
N
O
O
O-
P
O
O-
UDPG
CH2OH
CH2OH
O
O-UDP
UDPG
+
UDP
CH2OH
O
O
O
glycogen primer (n)
CH2OH
CH2OH
O
O
GLYCOGEN
SYNTHASE
CH2OH
O
O
CH 2 O
H
H
H
OH
OH
O
O
glycogen (n+1)
O
O
Glycogenesis
glycogen synthase
oligo  1,6-glucantransferase
Debranching
glycogen
synthase
oligo  1,6-glucantransferase
Debranching
Glycogenolysis
Glycogenolysis : glycogen  glucose
• In times of need the body needs to mobilize its’ fuel stores
• Hepatic glycogen not sufficient during 12 hr fast
• Glycogen degradation
• Occurs in cytosol
• Signal that glucose is needed is given by hormones
– epinephrine stimulates glycogen breakdown in muscle
– glucagon which stimulates glycogen breakdown in liver in
response to low BG
– used to sustain blood glucose level between meals and to provide
energy during an emergency/exercise
phosphorylase a
phosphorylase a
Glycogenolysis
1,4 glucose 1-phosphate
glucan transferase
glucosidase
Debranching has two enzyme
activities in one peptide: oligo 
1,4 1,4-glucantransferase and 
1,6-glucosidase
phosphorylase a
1 glucose
12 glucose 1-phosphate
Glycogen Phosphorylase Regulation
• Glycogen phosphorylase
– exists in a “b” inactive form (dephosphorylated) and an
“a” active form (phosphorylated)
– phosphorylase kinase converts glycogen phosphorylase
to active form “a” via addition of inorganic phosphate
• phosphorylase kinase also exists in an active “a” and an
inactive “b” form
– activated by cAMP-dependent protein kinase; it is also activated
by calcium ions
– PK is activated by glucagon and epinephrine
» via 2nd messenger cAMP
Glycogen Phosphorylase Regulation
• Glycogen phosphorylase “a” (active) is converted to “b” form
by phosphoprotein phosphatase
– Stimulated by insulin
• Glycogen phosphorylase can also be regulated by allosterically
– GP “b” inactive form can be converted to GP “b” active form by
high AMP
– GP “b” active form can be converted back to GP “b” inactive form
by high ATP
hormons:glucagon, epinephrine
active
adenylate
cyclase
ATP
Regulation of
Glycogenesis and Glycogenolysis
inactive
adenylate
cyclase
cAMP
inactive
protein
kinase A
ATP
active
protein
kinase A
P
phosphorylase b kinase
ADP
ATP
ATP
H2O
ADP
ADP
P
P
glycogen
synthase
(active)
Pi
phosphorylase b kinase
phosphorylase b phosphorylase a
glycogen
synthase
(inactive)
Pi
H2O
glycogenolysis
Pi
protein
phosphatase-1
H2O
glycogenesis
inhibitor-1
(inactive)
ATP
inhibitor-1
(active)
P
The significance of glycogenesis and glycogenolysis
- Liver glycogen (as much as 10% of liver wet
weight) functions as a glucose reserve for
maintaining blood glucose concentration
- Muscle glycogen (total 400 gram) serves as a
fuel reserve for synthesis of ATP within that
tissue
Section 6 *** Gluconeogenesis
• Synthesis of glucose from non-CHO precursors
– Lactate, most amino acids and glycerol ***
– Lactate and amino acids (except leucine and lysine)
are converted to either pyruvate or OAA
(oxalloacetate)
– Glycerol is converted (phosphorylated) to G3P and
then to dihydroxyacetone phosphate
• Occurs primarily in liver, sometimes kidney
PO4
Phosphatase
Blood
Glucose
H2 O
Glucose
Kinase
Ribose 5-PO4
G6P
Glycogen
F6P
PO4
Kinase
Phosphatase
F1,6bisP
DHAP
Gluconeogenesis
H2 O
Gly-3-P
1,3bisPGA
Kinase
3PGA
2PGA
PEP
Kinase
L-lactate
Pyruvate
OAA
Gluconeogenesis
• Reversal of glycolysis except at 3 steps
– HK(GK), PFK and PK
• 3 Steps need to be bypassed
Hexokinase and Phosphofructokinase are bypassed by
glucose 6 phosphatase and fructose 1,6-bisphosphatase
Pyruvate Kinase bypass involves formation of OAA as an
intermediate
– OAA in mitochondrial matrix cannot directly cross
membrane so is converted to malate
Gluconeogenesis
• Bypass of PK reaction continued
– Malate and aspartate can transverse mitochondrial
matrix
• converted back to OAA in cytoplasm
– OAA is decarboxylated and phosphorylated to PEP by
PEP carboxykinase
• Carbon skeletons of many amino acids that enter
TCA cycle can thus be used for glucose synthesis
(glucogenic amino acids)
Bypasses in Gluconeogenesis-1 (2 reactions)
Pyruvate Carboxylase (Gluconeogenesis) catalyzes:
pyruvate + HCO3- + ATP  oxaloacetate + ADP + Pi
PEP Carboxykinase (Gluconeogenesis) catalyzes:
oxaloacetate + GTP  PEP + GDP + CO2
Pyruvate Carboxylase
PEP Carboxykinase
O
O
O
C
C
-
O
C H3
HC O 3
G T P G DP
O
-
oxaloacetate
-
C
C
CO2
C
O
pyruvate
O
C H2
-
O
O
C
AT P ADP + P i
C
O
-
O PO 3 2
C H2
PEP
-
Bypasses in Gluconeogenesis-2
glycolysis
ADP
ATP
Mg2+
Fructose 1,6-2 PO4
Fructose-6-PO4
Fructose 1,6 bi-sphosphatase
H2 O
PO4
Gluconeogenesis
Bypasses in Gluconeogenesis-3
Glucose-6-Phosphatase (Gluconeogenesis) catalyzes:
glucose-6-phosphate + H2O  glucose + Pi
Glucose 6 phosphatase
6 C H O PO 22
3
5
H
4
OH
O
H
OH
3
H
C H2 O H
H
1
H
2
OH
OH
glucose -6 phosphate
H2 O
O
H
H
OH
H
+
H
OH
OH
H
glucose
OH
Pi
Substrate cycle is a pair of opposed irreversible reactions
Substrate cycle or futile cycle: nothing is accomplished but
the waste of ATP. In substrate cycle, ATP is formed in one
direction and then is hydrolyzed in the opposite direction.
Substrate cycle produces net hydrolysis of ATP
We must remember that the direction of the substrate cycle
is strictly controlled by allosteric effectors to meet the needs of
the body for energy
Glucose Paradox
• Evidence that glucose ingested during a meal is not
used to form glycogen directly
• Glucose is first taken up by RBCs in bloodstream and
converted to lactate by glycolysis
• Lactate is taken up by liver and converted to G6P by
gluconeogenesis
• G6P converted to glycogen
The significance of gluconeogenesis
1. To keep blood sugar level stable
2. To replenish liver glycogen
3. To clear the products of other tissues’ metabolites from the
blood
4. To convert glucogenic amino acids to glucose
5. To regulate acid-base balance
phosphoenolpyruvate carboxykinase
induces biosynthesis
gluconeogenesis
alpha-ketoglutarate
NH3
H+
NH4+
glutamic acid
NH3
glutamine
H+
glucose
NH4+excreted in
urine and pH
raised in blood
Na+ absorbed
urine
** Cori Cycle（Muscles lack G6-phosphatase ）
- used to prevent high blood lactate levels and to fuel muscle activity
- l-actate leaves muscle cells
- transported via blood to liver
- liver converts to glucose
- glucose released back into circulation
- returned to muscles
Regulation of gluconeogenesis and glycolysis
F-6-P
F-1,6-biphosphatase
ATP
citrate
ADP
AMP
F-2,6-BP
F-1,6-BP
phosphofructokinase-1
F-1,6-BP
glycolysis
insulin
gluconeogenesis
glucokinase
pyruvate carboxylase
phosphofructokinase-1
phosphoenolpyruvate carboxykinase
pyruvate kinase
fructose 1,6-biphosphatase
glucose 6-phosphatase
glucagon
Glucocorticoids
epinephrine
***** Section VII Blood Sugar and Its Regulation
Fate (outcome)
Origin (income)
Dietary supply
aerobic oxidation
Liver glycogen
glyc oge ne sis
Gluconeoesis
(non-carbohydrate)
Blood sugar
3.89~6.11mmol/L
PPP
C O 2 + H 2 O + e ne rgy
glycogen
o the r sac c haride s
non-c arbohydrate s
(lipids and som e am ino ac ids)
Other saccharides
8 .8 9 -- 1 0 .0 0 m m o l/L
( th re s h o ld o f k id ne y )
urine glucose
Regulation of high Blood Sugar
H ig h b lo o d s u g ar le v e l
( h y p e rg ly c e m ia)
insulin
insulin re c e ptor
a c ti v e tra n s p o r t
in m u s c le an d
a d i p o s e ti s s u e
c e lls ( n o t in liv e r
a n d b ra i n )
cAMP
1
4
m odulating system
3
5
5
6
glyc olysis
and ae ro bic
o xidatio n
2
gluc o ne o ge ne sis
2
glycogenolysis
lipogenesis
glycogenesis
lipolysis
pro te in synthe sis
Regulation of Low Blood Sugar
Low blood sugar level
(hypoglycemia)
glucagon
cAMP
Modulating system
1
hepatic
glycogenolysis
3
4
3
1
2
hepatic
glycogenesis
glycolysis
gluconeogenesis lipolysis transport of
glucogenic
amino acids
选择题练习
糖代谢
1. 糖类最主要的生理功能是(
A 提供能量
B 细胞膜组分
C 软骨的基质
D 信息传递
E 免疫作用
)
2. 关于糖类消化吸收的叙述,错误的是(
A 食物中的糖主要是淀粉
B 消化的部位主要是小肠
C 部分消化的部位可在口腔
D 胰淀粉酶将淀粉全部水解成葡萄糖
E 异麦芽糖酶可水解-1,6-糖苷键
)
3. 关于糖酵解途径中的关键酶正确的是(
A 磷酸果糖激酶-1
B 果糖双磷酸酶-1
C 磷酸甘油酸激酶
D 丙酮酸羧化酶
E 果糖双磷酸酶-2
)
4. 1分子葡萄糖在有氧或无氧条件下经酵解途
径氧化产生ATP分子数之比为(
)
A 2
B 4
C 6
D 19
E 36
5. 1分子乙酰CoA经三羧酸循环氧化后的产物是(
A 柠檬酸
B 草酰乙酸
C 2CO2+ 4分子还原当量
D CO2+H2O
E 草酰乙酸+CO2
)
6.
三羧酸循环主要在细胞的哪个部位进行?
A 胞液
B 细胞核
C 微粒体
D 线粒体
E 高尔基体
7. 磷酸戊糖途径是在哪个亚细胞部位进行的?
A 胞液中
B 线粒体
C 微粒体
D 高尔基体
E 溶酶体
8. 磷酸戊糖途径主要的生理功用(
A 为核酸的生物合成提供核糖
B 为机体提供大量NADPH+H+
C 生成6-磷酸葡萄糖
D 生成3-磷酸甘油醛
E 生成6-磷酸葡萄糖酸
)
9. 关于糖原合成的叙述错误的是(
)
A 葡萄糖的直接供体是UDPG
B 从1-磷酸葡萄糖合成糖原不消耗高能磷酸键
C 新加上的葡萄糖基连于糖原引物非还原端
D 新加上的葡萄糖基以-1,4糖苷键连于糖原引物上
E 新加上的葡萄糖基连于糖原引物C4上
10. 下例哪种酶不是糖异生的关键酶?
A 丙酮酸羧化酶
B 磷酸烯醇式丙酮酸羧基酶
C 磷酸甘油酸激酶
D 果糖双磷酸酶
E 葡萄糖6-磷酸酶
11. Which one is the main organ that
regulate blood sugar metabolism?
A brain
B kidney
C liver
D pancreas
E adrenal gland
12. The end product of glycolytic pathway
in human body is ( )
A CO2 and H2O
B pyruvic acid
C acetone
D lactic acid
E oxalacetic acid
13. Which one can promote synthesis of
glucogen, fat and protein simultaneously?
A glycagon
B insulin
C adrenaline
D adrenal cortex hormone
E glucocorticoid
14. Which one is the allosteric inhibitor
of 6-phosphofructokinase-1?
A 1,6-diphosphofructose
B 2,6 -diphosphofructose
C AMP
D ADP
E citric acid
15. 关于糖酵解的叙述,下列那些是正确的?
A 整个过程在胞液中进行
B 糖原的1个葡萄糖单位经酵解净生成2分子ATP
C 己糖激酶是关键酶之一
D 是一个可逆过程
E 使1分子葡萄糖生成2分子乳酸
16. 三羧酸循环中,不可逆的反应有(
A 柠檬酸 → 异柠檬酸
B 异柠檬酸 → -酮戊二酸
C -酮戊二酸 → 琥珀酰CoA
D 琥珀酸 → 延胡索酸
E 苹果酸 → 草酰乙酸
)
17. 如果摄入葡萄糖过多,在体内的去向是(
A 补充血糖
B 合成糖原储存
C 转变为脂肪
D 转变为唾液酸
E 转变为非必需脂肪酸
)
18. 胰岛素降血糖的作用是(
)
A 促进肌肉脂肪等组织摄取葡萄糖
B 激活糖原合成酶促糖原的合成
C 加速糖的氧化分解
D 促进脂肪动员
E 抑制丙酮酸脱氢酶活性
19. The cofactors of pyruvic dehydrogenase
complex is ( )
A thioctic acid
B TPP
C CoA
D FAD
E NAD+
20. The high-energy compounds produced by substrate
level phosphorylation in glyco-aerobic oxidation are ( )
A ATP
B GTP
C UTP
D CTP
E TTP
Thank you for your tolerance！