Download Glucose

Chap 4
Metabolism of
Carbohydrates
目录
Substance metabolism
目录
Relationship of each metabolism
External substance → internal subtance
Assimilation
Metab
olism
Micromolecule→Biomacromolecule
Anabolism
Endergonic
reaction
Exergonic
reaction
Energy
metabolism
Substance
metabolism
Dissimilation Biomacromolecule→Micromolecule
Catabolism
Internal substance → External substance
目录
 Definition of carbohydrate (saccharide)
Carbohydrates: Carbohydrates are
polyhydroxy aldehydes or ketones,
or substances that yield such
compounds on hydrolysis.
目录
classes and structure of carbohydrates:
Carbohydrates are classified into four
types according to their hydrolysates:

monosaccharide

oligosaccharide

polysaccharide

glycoconjugate
目录

monosaccharide
It’s the simplest of the carbohydrates that could not be
hydrolyzed any more.
glucose
（aldohexose）
fructose
（ketohexose）
O
H
HO
H
H
CH2OH
O
H
H
H
H
OH
H
OH
OH HO
H
OH
OH
OH
OH
OH
O
O
HO
H
H
OH
H
OH
OH
CH 2OH
HOH 2C
H
OH
H
OH
H
OH
galactose
（ aldohexose ）
ribose
（aldopentose）
O
O
H
HO
OH
CH2OH
H
HO
HO
H
H
OH
OH
OH
H
OH
H
H
OH
H
H
OH
H
OH
H
OH
OH
OH
O
HOH 2C
H
H
HO
OH
H
OH
H
oligosaccharide

Consist of short chains of monosaccharide units, or residues, joined
by characteristic linkages called glycosidic bonds. The most abundant
Are the disaccharides, with two monosaccharide units.
The common disaccharides:
maltose：glucose —
glucose
sucrose：glucose —
fructose
lactose：glucose —
galactose
目录

polysacchride
The polysaccharides are sugar polymers containing
more than 20 or so monosaccharide units, and some
have hundreds or thousands of units.
The common polysaccharides：

starch

glycogen

cellulose
目录
• Starch —— The most important storage
polysaccharides are starch in plant cells
Starch
granules
• Glycogen —— glycogen are stored forms of fuel in
animal cells
• cellulose —— the skeleton of plants
ß1-4 linkage
hydrogen bond
microfibril
Individual cellulose
molecule
fiber

glycoconjugate
the informational carbohydrate is covalently joined to a
protein or a lipid to form a glycoconjugate, which is
the biologically active molecule.
The common glycoconjugates :
glycolipid：a compound that consists of a lipid and a
carbohydrate
glycoprotein：have one or several oligosaccharides
of varying complexity joined covalently
to a protein.
目录
Part I
Introduction
目录
1. The main physiological function of
carbohydrate: Oxidation of fuel
The main function of carbohydrates is to provide
your body with energy and carbon.
Source of material for anabolism
e.g. Carbohydrate provides material
for synthesis of amino acid, nucleotide,
coenzyme, fatty acid, or other metaboli
Structural
elements of cells and tissues
c intermediate.
e.g. Carbohydrates are
components of glycoprotein,
proteoglycans and glycolipids.
目录
2. Digestion and absorption of carbohydrates

Digestion of carbohydrates:
For most humans, starch is the major
source of carbohydrates in the diet which
including plant starch, Animal glycogen,
maltose, sucrose, lactose and glucose.
 Digestion site：most in the small
intestine,
some in
the mouse
目录
 Process of digestion：
Starch
Oral
cavity
Enteric
cavity
α-amylase in saliva
α-amylase in pancreatic
Maltose + maltotriose
(40%) (25%)
brush
border of
Intestinal
epithelial
cells
α-limit dextrin + isomaltose
(30%)
(5%)
α-limit dextrinase
α-glucosidase
Glucose
目录
Despite the fact that humans cannot digest
cellulose (lacking an enzyme to hydrolyze the (ß 1,4)
linkages), cellulose is nonetheless a very important
part of the healthy human diet. This is because it
forms a major part of the dietary fiber that we know
is important for proper digestion. Since we cannot
break cellulose down and it passes through our
systems basically unchanged, it acts as what we call
bulk or roughage that helps the movements of our
intestines.
目录
absorption of carbohydrates
 absorption position :
small intestine
The upper
 Absorption Type ：monosaccharide
目录
Absorption mechanism
Lumen
Mucosal cells
of Intestinal
Portal
K+
ATP
+
Na
ADP+Pi
PUMP
Na+
G
Brush
border
cellular inner
membrane
Na+-dependent glucose transporter, SGLT
目录
3.Overview of carbohydrate metabolism

Glucose are transported into cells
Lumen of
small intestinal
SGLT
Intestinal epithelial cells
portal
A variety of tissue
cells
GLUT
Circulation
liver
This process is dependent on glucose
transporter (GLUT).
目录

Extracellular
Extracellular
α、β-amylase
intestinal（amylase、oligase）
Polysaccharide
and
oligosaccharide

monosaccharide
(glucose)
intracellular
Phosphorylase
glycogen
Activation
hydrolysis
Transferase
Debranching
enzyme
Branchedchain break
Phosphorylase
Activation
hydrolysis
目录
The sources and outlet of blood glucose
aerobic
conditions
CO2 + H2O
Provide energy
Carbs in food
Pyruvate
Digestion
absorption
Bread down
glycogen
glycolysis
Blood
glucose
anaerobic
conditions
lactate
Synthesis of
glycogen
liver (muscle)
glycogen
PPP
Gluconeogenesis
anabolism
Other carbs
Non-sugar substances
Fat, amino acid
目录
Part II
Glycolysis
目录
 Glycolysis: A process in which glucose is
partially broken down to two molecules of
pyruvate (it is converted into lactate finally )
by cells in enzyme reactions that do not need
oxygen. Glycolysis is also called anaerobic
oxidation.
 Position of glycolysis：cytoplasm
目录
1. Glycolysis Has Two Phases:
 Phase I------ glycolytic pathway: The sixcarbon glucose break down into two
molecules of the three-carbon pyruvate.
 Phase II: Pyruvate is converted to lactate.
目录
Phase I------ glycolytic pathway:
The six-carbon glucose break down into
two molecules of the three-carbon pyruvate
1. Phosphorylation of Glucose
目录
 Hexokinase, which catalyzes the entry of free
glucose into the glycolytic pathway, is a regulatory
enzyme. There are four isozymes (designated I to
IV). The predominant hexokinase isozyme of liver
is hexokinase IV (glucokinase).
 Characteristic:①Low affinity to glucose;
②Regulated by hormone;
 Glucokinase play a critical role in the maintenance
of blood glucose and metabolism of carbohydrates.
目录
2. Conversion of Glucose 6-Phosphate
to Fructose 6-Phosphate
目录
3. Phosphorylation of Fructose 6Phosphate to Fructose 1,6-Bisphosphate

6-phosphfructokinase-1
目录
4. Cleavage of Fructose 1,6-Bisphosphate
+

Aldolase
目录
5. Interconversion of the Triose
Phosphates
目录
6. Oxidation of Glyceraldehyde 3Phosphate to 1,3-Bisphosphoglycerate
目录
7. Phosphoryl Transfer from 1,3Bisphosphoglycerate to ADP
The formation of ATP
by phosphoryl
group transfer from a
substrate such as 1,3bisphosphoglycerate
is referred to as a
substrate-level
phosphorylation
目录
8. Conversion of 3-Phosphoglycerate to
2-Phosphoglycerate
目录
9. Dehydration of 2-Phosphoglycerate to
Phosphoenolpyruvate
目录
10. Transfer of the Phosphoryl Group
from Phosphoenolpyruvate to ADP
COOH
C O
ADP
P
K+
Mg2+
ATP
COOH
C=O
pyruvate kinase
CH2
Phosphoenolpyruvate
CH3
Pyruvate
目录
Phase II:
COOH
Pyruvate is converted to lactate.
NADH + H+
NAD+
COOH
CHOH
C=O
Lactate dehydrogenase (LDH)
CH3
CH3
Pyruvat
Lactate
e
NADH+H+ needed in this reaction is
provided by Oxidation of Glyceraldehyde 3Phosphate in step 6 of glycolytic pathway.
目录
Glu
E1
E2 F-1, 6-2P
ATP ADP
G-6-P
F-6-P
ATP ADP
Dihydroxyacetone
phosphate
E1:Hexokinase
E2: Phosphofructokinase-1
E3:Pyruvate kinase
Glyceraldehyde 3phosphate
NAD+
NADH+H+
2×1,3-Bisphosphoglycerate
ADP
ATP
2× 3-Phosphoglycerate
lactate
NAD+
Glycolysis
2× 2-Phosphoglycerate
NADH+H+
ATP ADP
2×pyruvate
2× Phosphoenolpyruvate
E3
目录
Summary of glycolysis
 Position of glycolysis：cytoplasm
 Glycolysis is an anaerobic process through which ATP
is synthesized .
 There are three irreversible steps in the process.
ATP
ADP
G
G-6-P
Hexokinase
ATP
F-6-P
Phosphofructokinase-1
ADP
PEP
ADP
F-1,6-2P
ATP
Pyruvate kinase
Pyruvate
目录
 Method and Quantity of energy-producing:
Method： substrate-level Phosphorylation
Quantity of ATP：From G
2×2-2= 2ATP
From Gn 2×2-1= 3ATP
 Fates of lactate:
Lactate is released into blood and metabolized in liver
Decomposition
Cori cycle（glyconeogenesis）
目录
Many hexose besides glucose
meet their catabolic fate in
glycolysis, after being transformed
into hexosephosphate
Mannose
hexokinase
Mannose 6-phosphate
Glu
galactose
galactokinase
UDP-galactose
ATP
ADP
G-6-P
mutase
Glucose
1-phosphate
F-6-P
ATP
Fructose
ADP
F-1,6-2P
Pyruvae
目录
2. Regulation of Glycolysis: 3 key enzymes
① Hexokinase
Key
Enzymes
② Phosphofructokinase-1
③ Pyruvate kinase
① allosteric regulation
Method of
regulatio
n
② covalent modification
目录
1.Phosphofructokinase-1 (PFK-1) is the most
important enzyme to regulate the yield of glycolysis
 Allosteric
regulation
allosteric activator：AMP; ADP;
F-1,6-2P; F-2,6-2P
allosteric inhibitor：citrate; ATP（High level）
目录
ATP regulate the acitivity of
Phosphofructokinase-1 (PFK-1)
ATP binding site
Regulation
substrate-binding site in active center
（low level）
allosteric regulation site
beside active center（high level）
activation
inhibition
目录
Fructose 2,6-bisphosphate regulate the activity
of Phosphofructokinase-1 (PFK-1)

Fructose 2,6-bisphosphate is the strongest allosteric
activator of Phosphofructokinase-1

When fructose 2,6-bisphosphate binds to its
allosteric site on PFK-1, it increases that enzyme’s
affinity for its substrate, fructose 6-phosphate, and
reduces its affinity for the allosteric inhibitors ATP
and citrate.
目录
AMP
Citrate
Glucagon
–
+
PFK-2
FBP-2
（active）
ATP
cAMP
（inactive）
6-PFK-2
ATP
F-6-P
Activate
Phosphoprotein
phosphatase
PKA
F-2,6-2P
FBPase-2
ATP
+
ADP
P
PFK-2
FBP-2
（inactive）
（active）
ADP
–/+
PFK-1
+ +
F-1,6-2P
AMP
Pi
P
Pi
+
–
Citrate
PKA：protein kinase A

Glucogen
Fat
Glucose
Fatty acie＋ Glycerine
Ⅱ
Protein
Acetyl-CoA
Oxaloacetate
Malate
Ⅲ
Amino acid
Citrate
α-Ketoglutarate
Succinate
CO2
Succinyl-CoA
2H＋
Oxidative
phosphorylation
ADP＋Pi
ATP
目录
2. Pyruvate kinase is the second regulation point of
glycolysis
 Allosteric
regulation
allosteric activator：F-1,6-2P
allosteric inhibitor：Alanine; ATP.
目录

Covalent modification regulation
Pi
phosphoprotein
phosphatase
Pyruvate
kinase
（active）
Pyruvate
P
kinase
（inactive）
ATP
Glucagon
ADP
PKA, CaM kinase
PKA：protein kinase A
CaM: calmodulin
目录
3. Hexokinase is regulated by feedback suppression
 Except for liver glucokinase, hexokinase is suppressed
by feedback of glucose 6-phosphate.
 Long-chain fatty acyl CoA is a allosteric inhibitor of
glucokinase.
 Insulin promote the synthesis of glucokinase throuth
inducing it’s transcription.
目录
3. The main physiological function of
glycolysis: provide energy quickly under
anaerobic conditions
 Glycolysis is an effective way to get energy under anaerobic
conditions.
 The glycolytic breakdown of glucose is the sole source of metabolic
energy in some mammalian tissues and cell types.
① Cells without mitochondria：erythrocytes
② Metabolic active cells：leucocyte、myeloid cell
目录
Part III
Aerobic Oxidation
of Carbohydrate
目录

Definition
The aerobic oxidation of
carbohydrates is referred
to glucose is oxidized to
H2O and CO2 under
aerobic conditions. It’s the
main energy supply mode.
Glycolysis
（cytoplasm）
oxidative
phosphorylation
（mitochondria）
Position：cytoplasm
and
mitochondria
目录
1. There are four phases in the process of
aerobic oxidation of carbohydrates
G（Gn）
Phase I：Glytolytic pathway
cytoplasma
Phase II：Oxidative decarboxylation
of pyruvate
Acetyl-CoA
Phase III：TAC cycle
mitochondria
Phase IV: Oxidative phosphorylation
[O]
H2O
ATP
ADP
Pyrutate
NADH+H+
FADH2
Citrate
TAC
CO2
目录
1. Glucose break down into two molecules of the
three-carbon pyruvate in glycolytic pathway
2. Pyruvate is oxidized to Acetyl-CoA and CO2 in
mitochondria
 Overall reaction :
NAD+ , HSCoA
CO2 , NADH + H+
Acetyl-CoA
Pyruvate
pyruvate dehydrogenase
complex
目录
HSCoA
 The composition of pyruvate
dehydrogenase complex
NAD+
enzymes
E1：pyruvate dehydrogenase
Coenzymes
TPP
S
E2：dihydrolipoyl transacetylase
lipoate（L
HSCoA
)
S
E3：dihydrolipoyl dehydrogenase FAD, NAD+
目录
 Oxidative decarboxylation of pyruvate to
acetyl-CoA by the PDH complex.
1. Pyruvate reacts with the bound thiamine pyrophosphate (TPP) of
pyruvate dehydrogenase (E1), undergoing decarboxylation to the
Hydroxyethyl derivative.
2. Form the acetyl thioester-E2 of the reduced lipoyl group.
3. The -SH group of CoA replaces the -SH group of E2 to yield acetyl
CoA and the fully reduced (dithiol) form of the lipoyl group.
4. Dihydrolipoyl dehydrogenase (E3) promotes transfer of two
hydrogen atoms from the reduced lipoyl groups of E2 to the FAD
prosthetic group of E3, restoring the oxidized form of the lipoyllysyl
group of E2.
5. The reduced FADH2 of E3 transfers a hydride ion to NAD+ forming
NADH.
目录
1.Generation of
-hydroxyethyl-TPP
CO2
2.Generation of
Acyl lipoyllysine
NADH+H+
5. Generation of
NADH+H+
NAD+
CoASH
3.Generatin
of AcetylCoA
4. Generation of
lipoyllysine
2. TCA is a circulation response system based
on the formation of citric acid as starting
material
 overview
Tricarboxylic Acid Cycle (TAC) is also named
citric acid cycle，because the first intermediate
product is citric acid containing three carboxylor,
or the Krebs cycle (after its discoverer, Hans
Krebs).
 Position
of reaction ：mitochondria
目录
1. The Citric Acid Cycle Has Eight Steps
1. The condensation of acetyl-CoA with oxaloacetate to
form citrate.
2. Formation of Isocitrate via cis-Aconitate.
3. Oxidation of Isocitrate to α-Ketoglutarate and CO2.
4. Oxidation of α-Ketoglutarate to Succinyl-CoA and
CO2.
5. Conversion of Succinyl-CoA to Succinate.
6. Oxidation of Succinate to Fumarate.
7. Hydration of Fumarate to Malate.
8. Oxidation of Malate to Oxaloacetate
目录
H2O
H2O
②
①
NADH+H+
H2O
CoASH
②
NAD+
①citrate synthase
②aconitase
③isocitrate dehydrogenase
④α-ketoglutarate dehydrogenase complex
+
NAD
GTP
GDP ⑤succinyl-CoA synthetase
nucleoside diphosphate kinase
⑥succinate dehydrogenase
NADH+H+
⑦
⑦fumarase
③
⑧malate dehydrogenase
H2O
FADH
+
⑧
ADP
⑥
NAD
2
ATP
FAD
GDP+Pi
GTP
NADH+H+
④
⑤
CoASH
CO2
CoASH
CO2
⑴ Formation of Citrate:
Inreversible reaction
目录
⑵ Formation of Isocitrate
目录
⑶ Oxidation of Isocitrate to α-Ketoglutarate ：
Mg2+
Inreversible reaction
目录
⑷Oxidation of α-Ketoglutarate to Succinyl-CoA
Inreversible reaction
目录
⑸substrate-level phosphorylation：Conversion of
Succinyl-CoA to Succinate
The only substrate-level phosphorylation
reaction which produced GTP in TAC
目录
⑹ Oxidation of Succinate to Fumarate:
目录
⑺Hydration of Fumarate to Malate：
H2O
目录
⑻Oxidation of Malate to Oxaloacetate：
目录
Summary：
 Definition of TAC ： Acetyl-CoA entered the cycle by
combining with oxaloacetate to form citrate containing three
carboxyls. Two carbon atoms emerged from the cycle as CO2
from the oxidation of isocitrate and α-ketoglutarate. The
energy released by these oxidations was conserved in the
reduction of three NAD+ and one FAD and the production of
one ATP or GTP. At the end of the cycle a molecule of
oxaloacetate was regenerated.
 Position of TAC reaction : mitochondria
目录
Four
dehydrogenation
One substrate level
osphorylation
TAC
Three key
enzymes

One substrate level prosphorylation、
Two decarboxylation、
Three key enzymes、

Four dehydrogenation


Two
decarboxylation
目录
 Highlight of TAC：
Following a cycle :
• Consumption: one Acetyl-CoA；
• Undergo: four dehydrogenation，two decarboxylation，
one substrate level prosphorylation；
• Generation: one FADH2，three NADH+H+，two CO2，
one GTP；
• Key enzyme：citrate synthase， isocitrate dehydrogenase,
α-ketoglutarate dehydrogenase complex.
 The whole cycle reaction is irreversible.
目录
 intermediate product of TAC:
The intermediate products of TAC performed
as a catalyst without change of it’s quantity.
Oxaloacetate or other intermediate products can
neither be synthesized directly from Acetyl-CoA,
nor be oxidized directly to CO2 and H2O in TAC.
目录
Apparently， Oxaloacetate which does not be
consumed in TAC could be used in recycling.
In fact:
Ⅰ. Various metabolic pathways and their regulation in
organism are linked and interacted each other. Some
intermediate products of TAC could integrate metabolism
of carbohydrate and other material by converted into
other substances.
e.g.
Oxaloacetate
α-ketoglutarate
citrate
Succinyl-CoA
aspartate
glumatic acid
fatty acid
porphyrin
目录
Ⅱ. When the carbohydrate supply is insufficient, it may
cause circulatory disturbance of TAC. So Acetyl-CoA
could by generated by pyruvate which is formed
through the decarboxylization of malate or
Oxaloacetate.
NAD+
NADH + H+ CO2
Malate
Pyruvate
malic enzyme
CO2
Oxaloacetate
Pyruvate
oxaloacetic decarboxylase
Oxaloacetate must be replenished continuously
目录
 The source of oxaloacetate：
Citrate
Acetyl-CoA
CO2
Pyruvate
pyruvate
carboxylase
Oxaloacetate
Citrate lyase
malate
dehydrogenase
Malate
NADH+H+
Glu
GOT
NAD+
α-ketoglutarate
Aspartate
目录
3. Aerobic oxidation of carbohydrate is the main
method to get ATP of organism.
In oxidative phosphorylation, passage of two
electrons from NADH to O2 drives the formation of
about 2.5 ATP, and passage of two electrons from
FADH2 to O2 yields about 1.5 ATP.
NADH+H+
FADH2
[O]
H2O、2.5ATP
[O]
H2O、1.5ATP
目录
Phase I
(Cytoplasma)
Phase II
(Mito matrix)
Phase III
(Mito matrix)
目录
 Aerobic oxidation of carbohydrate is the main method
to get ATP of organism. The generation of energy is
not only efficient but also gradually in this way. The
energy of oxidations in the cycle is efficiently conserved
by the formation of ATP.
目录

1.
TCA cycle has important
physiological significance in the
metabolism of three major nutrients
TCA cycle is the last metabolic pathway of three
nutrients to provide reducing equivalents for the
generation of ATP in oxidative phosphorylation
through four dehydrogenations.
2.
TCA cycle is a key point to communicate the
metabolism of protein, carbohydrate and fat.
目录

Glucogen
Fat
Glucose
Fatty acie＋ Glycerine
Ⅱ
Protein
Acetyl-CoA
Oxaloacetate
Malate
Ⅲ
Amino acid
Citrate
α-Ketoglutarate
Succinate
CO2
Succinyl-CoA
2H＋
Oxidative
phosphorylation
ADP＋Pi
ATP
目录
4. The regulation of aerobic oxidation of
carbohydrate is dependent on the requirement
of energy.
Hexokinase
① Glycolytic pathway：
pyruvate kinase
Phosphofructokinase-1
Key
Enzyme ② oxidative
Pyruvate dehydrogenase
complex
decarboxylation
of pyruvate：
citrate synthase
③ TCA cycle：
α-ketoglutarate dehydrogenase
complex
isocitrate dehydrogenase
目录
 The
regulation of Pyruvate dehydrogenase complex
 allosteric regulation
allosteric inhibitor：Acetyl-CoA；NADH；ATP
allosteric activator：AMP；ADP；NAD+
this enzyme activity is turned off when ample fuel is available
in the form of fatty acids and acetyl-CoA and when the cell’s
[ATP]/[ADP] and [NADH]/[NAD+] ratios are high.
目录
 Covalent modification
glucagon
目录

TCA cycle is regulated by substrate,
products and the activity of key
enzymes.
 Three factors govern the rate of flux through
the cycle: substrate availability, inhibition by
accumulating
products,
and
allosteric
feedback inhibition of the enzymes that
catalyze early steps in the cycle.
目录
1．There are three key enzymes in TCA cycle:
 citrate synthase,
 Isocitrate dehydrogenase
 α-ketoglutarate dehydrogenase
目录
 The
regulation of TAC
Acetyl-CoA
– ATP Citrate NADH Succiny-CoA
+ ADP
① Effect of ATP、ADP
citrate
Oxaloacetate synthase
② inhibition by
accumulating products
Isocitrate
Malate
③allosteric feedback
FADH2
inhibition of the
enzymes that catalyze
early steps in the cycle.
④ others，e.g. Ca2+
activate enzymes
Citrate
NADH
isocitrate
– ATP
dehydrogenase
+ ADP Ca2+
α--Ketoglutarate
α-ketoglutarate
dehydrogenase
Ca2+
+
complex
Succiny-CoA – Succiny-CoA NADH
GTP
ATP
目录
2．The rates of TCA cycle and the other reactions of
its upstream or downstream are integrated.
 Under normal conditions, the rate of glycolysis is matched to the
rate of the citric acid cycle not only through its inhibition by high
levels of ATP and NADH, which are common to both the
glycolytic and respiratory stages of glucose oxidation, but also by
the concentration of citrate which play a allosteric inhibition to
PFK-1.
 The rate of oxidative phosphorylation play an important role in
the progress of TCA cycle.
目录
Because the activity of many enzymes in the
progress of oxidative phosphorylation is regulated by the
rates of ATP/ADP or ATP/AMP in cells.
2ADP
adenylate
kinase
ATP+AMP
In vivo ATP concentration is 50 times of AMP.
After above reaction, the change of ATP/AMP are
much bigger than the change of ATP，it played an
effective regulation by signal amplification
目录
5. The inhibiting effect of oxygen on the process
of fermentation
 Definition
Pasteur effect: The inhibiting effect of
oxygen on the process of fermentation.
 Mechanism
 Under aerobic conditions, NADH+H+ and pyruvate enter into
the mitochondria, then enters the citric acid cycle, where it is
completely oxidized.
 Under anaerobic conditions, pyruvate is reduced to lactate,
accepting electrons from NADH and thereby regenerating the
NAD+ necessary for glycolysis to continue.
目录
Part IV
Other Metabolism
Pathways of Glucose
目录
1.Pentose phosphate pathway produces
pentose phosphates and NADPH+H+
 Definition
Pentose phosphate pathway is the progress
of glucose produces pentose phosphates and
NADPH+H+, then the pentose phosphates is
converted into Glyceraldehyde 3-phosphate and
fructose 6-phosphate.
目录
1.
The progress of pentose phosphate
pathway has two phases:

Position：Cytosol

The reaction has two phases:
 Phase I: The Oxidative Phase
Produces Pentose Phosphates, NADPH+H+ and CO2
 Phase II：The Nonoxidative Phase
Including a series of group transfer.
目录
1．glucose 6-phosphate undergoes oxidation and to
form the pentose phosphates and NADPH
H
C
OH
glucose 6-phosphate
dehydrogenase
H
C
OH
NADP+
HO
C
H
H
C
OH
H
C
CH2O
O
H
C
OH
HO
C
H
H
C
OH
H
C
NADPH+H+
⑴
P
CH2O
glucose 6-phosphate
CO2
NADPH+H+
⑵
H 2O
O
P
H
C
OH
H
HO
C
H
H
C
OH
H
C
OH
P
6-Phosphoglucono-lactone 6-Phosphogluconate
CH2O
CH2OH
6-phosphogluconate
dehydrogenase
NADP+
CO
COO—
C=O
C=O
C
O
H
C
OH
H
C
OH
CH2O
P
Ribulose
5-phosphate
Ribose
5-phosphate
目录
NADP+
NADPH+H+
NADP+ NADPH+H+
G-6-P
CO2
Ribose
5-phosphate
 The glucose 6-phosphate dehydrogenase which
catalyze the first step is the key enzyme of the
pathway.
 H+ produced in two dehydrogenations were
accepted by NADP+ to generate NADPH + H+ .
 ribose phosphate generated in reaction is a very
important intermediated product.
目录
2．Enter the glycolysis by the group transfer reaction
 The significance of phase II is the transformation
of
ribose
to
fructose
6-phospherate
and
Glyceraldehyde 3-phosphate by a series of group
transfer reaction, then enter the glycolysis. So,
pentose phosphate pathway is also named pentose
phosphate shunt.
目录
Ribulose 5-phosphate (C5)
Xylulose 5phosphate
C5
Glyceraldehyde
3-phosphate
C3
Ribose
5-phosphate
C5
×3
Xylulose 5-phosphate
C5
Sedoheptulose
7-phosphate
Glyceraldehyde
3-phosphate
C7
C3
Erythrose
4-phosphate
Fructose
6-phosphate
C4
C6
Fructose
6-phosphate
C6
目录
glucose 6-phosphate(C6)×3
pentose
phosphate
pathway
3NADP+
3NADP+3H+
glucose 6-phosphate dehydrogenase
6-Phosphoglucono-lactone(C6)×3
Phase I
6-Phosphogluconate(C6)×3
3NADP+
3NADP+3H+
6-phosphogluconate dehydrogenase
CO2
Ribulose 5-phosphate(C5) ×3
Xylulose
5-phosphate C5c
Glyceraldehyde
3-phosphate C3
Ribose 5-phosphate
C5
Xylulose
5-phosphate C5c
Sedoheptulose
7-phosphate C7
Glyceraldehyde
3-phosphate C3
Erythrose
4-phosphate C4
Fructose
6-phosphate C6
Phase
II
Fructose
6-phosphate C6
目录
 reaction
formula:
3×glucose 6-phosphate + 6 NADP+
2×Fructose 6-phosphate
+
Glyceraldehyde 3-phosphate
+
6NADPH+H+
+
3CO2
目录
Characteristic of pentose phosphate pathway:
 Hydrogen receptor of dehydrogenation is NADP+ , to generate
NADPH+H+。
 Transaldolase and transketolase catalyze the interconversion of three-,
four-, five-, six-, and seven-carbon sugars, with the reversible conversion
of six pentose phosphates to five hexose phosphates.
 The reaction provides specialized intermediated product: ribose 5phosphate.
 One CO2 and two NADPH+H+ were generated by one G-6-P through
one decarboxylation and two dehydrogenation in a cycle.
目录
2. The pentose phospherate pathway is
regulated mainly by the ratio of NADPH/NADP+
 Glucose-6-phosphate dehydrogenase is the key
enzyme of the pentose phosphate pathway, the
activity of this enzyme decide the flow of glucose-6phosphate which enter the pathway.
 The G-6-P-D is inhibited by a high ratio of
NADPH/NADP+ and increased consumption of
NADPH .
 Therefore, the flow of pentose phospherate pathway
meets the needs of the cells for NADPH.
目录
3. the significance of pentose phospherate is the
generation of NADPH and ribose 5-phosphate
1．Provide ribose for biosynthesis of nucleotides.
2．Provide NADPH as hydrogen donor to participate in
various metabolic reactions
（1）NADPH is the hydrogen donor in various anabolic；
（2）NADPH participate the hydroxylation in vivo.
（3）NADPH could keep the regeneration of reduced
glutathione (GSH).
目录
oxidized glutathione
Reduced glutathione
A
AH2
2G-SH
G-S-S-G
NADP+
NADPH+H+
 Reduced glutathione is an important antioxidant which protect
protein or enzyme with –SH group from the damage of
oxidizing agents and peroxide in vivo.
 Reduced glutathione maintains the integrity of erythrocytes
membrane.
目录

Favism：
some people are Glucose 6-Phosphate Dehydrogenase
(G6PD) deficient. their erythrocytes will lyse after
ingestion of the beans (containing divicine or other
oxidizing agents), releasing free hemoglobin into the
blood (acute hemolytic anemia).
G6PD deficiency is a X-linked recessive genetic disease.
X-linked diseases usually occur in males. Males have only
one X chromosome. A single recessive gene on that X
chromosome will cause the disease. The geographic
distribution of G6PD deficiency is instructive. It is
common in the South than in the northern population
目录
Part V
Glycogenesis and
Glycogenolysis
目录
Structure of glycogen
Nonreducing ends
shape：branched polymer
MW：1,000,000～
10,000,000
Reducing end：one
Nonreducing ends：poly
Reducing
end
目录
Distribution of glycogen
Hepatic glycogen：
the glycogen content of the
liver is up to 8% of the fresh
weight.
Muscle glycogen：
the glycogen concentration
in muscle is 1%-2%.
Back
目录
1. Most anabolism of glycogen
occurred in liver and muscle.
 Definition：
The synthesis progress of glycogen from
monosaccharide is named glycogenesis.
 Monosaccharide:
Glucose (main), fructose, galactose …
 Position：
Cytoplasma of liver, muscle …
目录
Glucose is converted to glucose 6-phosphate
CH2OH
O H
H
OH
H
O H
H
OH
OH
H
ADP
Mg2+
H
HO
ATP
CH2OPO3H2
OH
glucose
Glucose + ATP
H
H
Glucokinase HO
OH
H
OH
glucose-6-phosphate
glucose-6-phosphate+ADP
Glucose-6-phosphate is isomerized to
glucose-1-phosphate
OH
O P O CH2
OH
OH
HO CH2
O
O
OH
OH
OH phosphoglucomutase OH
OH
glucose-6-phosphate
Glucose-6-phosphate
OH
O P
OH
O
HO
glucose-1-phosphate
Glucose-1-phosphate
The generation of UDP-glucose
CH2OH
UDPG
pyrophosphorylase
O H
H
OH
H
O
H
O
HO
UTP
P OH
OH
H
OH
glucose-1-phosphate
CH2OH
O H
H
OH
H2O
2Pi
UTP+ G-1-P
H
H
O
HO
PPi
O
H
O
P O P O ÄòÜÕ
urdine
OH HO
OH
UDPG
(uridine diposphate glucose)
UDPG+ PPi
The glucose in UDPG is attached to
glycogen primer
CH 2OH
O H
H
OH
H
O H
H
H
OH
urdine
P P ÄòÜÕ
HO
HO
H
CH2OH
CH2OH
OH
H
O
H
OH
H
H
H
O R
O
UDPG
OH
H
OH
H
H
Gn
(glycogen primer)
Glycogen synthase
UDP
Gn+
(glycogen)
O H
H
OH
H
CH2OH
CH2OH
CH 2OH
O H
H
OH
H
H
H
OH
OH
H
H
H
OH
H
H
O
O
O
HO
O
H
H
OH
R
The branching enzyme catalyze the formation of
new branches on glycogen
12~18G
Glycogen
synthase
Glycogen primer
Branching
enzyme
Rate-limiting enzyme
目录
Scheme of the synthesis
of glycogen
glucose
ATP
ADP
G-1-P
G-6-P
UTP
UDPG
PPi
Glycogen primer
Glycogen
UDP
(1→4 glucose unit)
Energy consumption
need primer
nonreducing end
Branching enzyme
Glycogen (1→4 and 1→6
glucose unit)
Back
目录
2. The production of glycogen degradation:
glucose could replenish the blood glucose
 Glycogen-degrading
The progress that glycogen is degraded to
glucose.
 Position:
Liver
 Production:
Glucose
目录
Glycogen is phosphorolytic cleavaged to G-1-P
糖原
Gn
H3PO4
PHOSPHORYLASE
Rate-limiting enzyme
糖 原 Gn-1
HO CH2
O
OH
OH
OH
O P
OH
HO
glucose-1-phosphate
O
Gn+ H3PO4
G-1-P + Gn-1
Nonreducing end
phosphorylase
Glucose-1-phospherate
Pi
Pi
G-1-P
The function of
debranching
enzyme
Debranching enzyme
Debranching enzyme
has two activities:
Debranching enzyme
G
α-1,4- transglycosylase
α-1,6- glycosidase
目录
G-1-P is converted to G-6-P
OH
O P O CH2
OH
HO CH2
O
OH
OH
OH
O P
OH
HO
glucose-1-phosphate
G-1-P
O
OH
glycophosphomutase
O
OH
OH
OH
glucose-6-phosphate
G-6-P
G-6-P is hydrolyzed to Glucose
H2O
CH2OPO3H2
H3PO4
O H
H
OH
H
H
HO
CH2OH
OH
H
H
Glucose -6 - phosphatase HO
OH
（liver）
H
O H
H
OH
OH
H
OH
glucose
glucose-6-phosphate
This enzyme is deficient in
brain and muscle
G-6-P+ H2O
Glucose + H3PO4
Glycogen
Gn+1
Pi
phosphorylase
Scheme of
the glycogendegradation
Gn
G-1-P
glucophosphomutase
Catabiosis of
carbohydrate
G-6-P
Glucose-6-phosphatase
H2O
Pi
Glucose
目录

The synthesis and degradation of glycogen
Gn+1
UDP
Gn
Pi
Glycogen synthase
Gn
UDPG
PPi
phosphorylase
UDPG pyrophosphorylase
UTP
G-1-P
glucophosphomutase
Glucose-6-phosphatase(liver)
G-6-P
G
Hexokinase (glucokinase)
目录
Comparison of liver glycogen and muscle
glycogen
liver glycogen
Muscle glycogen
Storage
90-100g
≤5%
200-500g
1-2%
Raw
material
cleavage
product
Monosaccharide/nocarbohydrate material
Glucose
Glucose
function
To maintain relatively
stable of blood glucose
consumption 12-18h after meal
lactate
To meet the energy
requirement of muscles
in strenuous exercise
After heavy exercise
目录
3. Glycogen synthesis and glycogen
三.糖原合成与分解受到彼此相反的调节
degradation are regulated by each other
Glycogen synthase
Key enzyme of
glycogen degradation
Key enzyme of
glycogen degradation
Key enzyme of
glycogen synthesis
active
Glycogen
synthase
inactive
Glycogen
synthase
Phosphorylase
P
phosphorylase
phosphorylase
inactive
phosphorylase
P
P active
目录
Hormone regulate the metabolism by cAMP-protein kinase
Hormone
Receptor
Cell membrane
G Protein cyclase
ATP
cAMP+PPi
R
c
c
R
cAMP
Protein kinase（active）
Protein kinase
（inactive）
ATP
Unphosphorylated
Protein kinase
covalent
modification
+
ADP
Phosphorylated
Protein kinase
Phosphorylation of integral protein
Change the process of physiology in cells
Cell membrane
目录
Hormone
regulate the
synthesis and
degradation of
liver glycogen
Adrenalin/
Glucagon
Adrenalin/
Glucagon
1、adenylcyclase
1
（inactive）
adenylcyclase（active）
2、ATP
2
cAMP
R、cAMP
3、protein kinase
Signifiance: because the
covalent modification of
enzyme is a enzymatic
reaction, a little signal
(hormone) could make a
large number of
enzymes to be modified
through accelerating
this enzymatic reaction,
then the signal is
amplified. Such
regulation is quickly and
efficiently
（inactive)
102
3
Protein kianse（active）
ATP
ADP
4
4、phosphorylase
kinase（inactive） Phosphorylase kinase
（active）
ATP
ADP
104
5
106
5、phosphorylase b
（inactive）
Phosphorylase a（active）
6
108
6、glycogen
G-1-P
blood
glucose
Glucose
G-6-P
目录
目录
Glucagon, adrenalin
adenylcyclase
+
Phosphorylase b kinase
adenylcyclase
ATP
+
cAMP
Protein kinase
+
Glucagon and adrenalin
regulate the synthesis
and degradation of
glycogen
+
Protein kinase
Phosphorylase b kinase
Glycogen synthase + Glycogen syntha
Phosphorylase b +
Cascade
amplification
effect
Phosphorylase a
Decrease the synthesis of glycogen
Enhance the degradation of glycogen
返回
目录
The regulation of synthesis and degradation of
liver glycogen





allosteric regulation
When the blood glucose
increase
G is an allosteric effector  phosphorylase (a)
The allosteric enzyme is susceptible to be inactive through
dephosphorylation catalyzed by phosphoprotein
phosphatase.
Meanwhile, the glycogen synthase is activated through
dephosphorylation catalyzed by phosphoprotein
phosphatase.
Result：G ，the synthesis of glycogen，the degradation
of glycogen
目录
The synthesis and degradation of muscle glycogen



Synthesis: same to liver glycogen (without three-carbons
pathway)
Degradation: different to liver glycogen, (without G6PE)
glycogenG-6-P glycolytic pathway
Regulation：adrenalin (mainly)
AMP: allosteric activate phosphorylase-b
ATP and G-6-P：inhibit phosphorylase-b
G-6-P: allosteric activate glycogen synthase
目录

Summary of regulation:
 There are two forms (active or inactive) of all key
enzymes, the two kinds of forms could change in each
other by phosphorylation and dephosphorylation.
 Bidirectional regulation：synthase and lytic enzyme
were regulated separately. e.g. enhance the synthesis
and decrease the degradation.
 Duel regulation：allosteric regulation and covalent
modificational regulation.
 There are cascade effect on the regulation of kcy enzyme.
 Difference of regulation on the liver and muscle glycogen:
e.g. glucagon degrade the liver glycogen,
adrenalin degrade the muscle glycogen.
目录
3. deficiencies of glycogen degrading
enzymes lead to glycogen storage disease
glycogen storage diseases is an inherited
metabolism disease. Deficiencies of glycogendegrading enzymes usually lead to
accumulation of glycogen in the liver or other
organs.
目录
Glycogen storage diseases
Type Enzyme deficiency
Organ affected
Structure of
glycogen
Ⅰ
G-6-P
Liver, kidney
normal
Ⅱ
α1→4 or 1→6 glucosidase
All organs
normal
Ⅲ
Debranching enzyme
Muscle, liver
More branch，
short peripheral
carbs chain
Ⅳ
Branching enzyme
All organs
Less branch，long
peripheral carbs
chain
Ⅴ
Muscle phosphorylase
muscle
normal
Ⅵ
Liver phosphorylase
Liver
normal
Ⅶ
phosphofructokinase
Muscle,
erythrocyte
normal
Ⅷ
Phosphorylase kinase
Liver
normal
目录
Part VI
Gluconeogenesis
目录

Definition：
Gluconeogenesis is the synthesis progress of
glucose or glucogen from non-carbohydrate
sources.

Position：
Cytoplasma and mitochondria of liver , kidney
cells.

Substrance：
Pyruvate, lactate, glycerine, glycogenic amino acid.
目录
1. Gluconeogenic pathway is not a
reversible reaction of glycolytic
pathway completely
gluconeogenic pathway is the synthesis
progress of glucose from pyruvate.

Progress：
 Most reactions of gluconeogenic pathway
and glycolytic pathway are shared and
reversible.
 Three irreversible reactions catalyzed by
three key enzymes in glycolysis must by
bypassed in gluconeogenesis.
目录
1. Pyruvate is converted to PEP by pyruvate
carboxylation bypass
ATP
Pyruvate
CO2
ADP+Pi
GTP
GDP
oxalacetate
①
PEP
② CO2
① pyruvate carboxylase, coenzyme is biotin (in
mitochondria).
② PEP-carboxykinase ( mitochondrion,
cytoplasma)
目录
目录

Oxaloacetate export to the cytosol from
mitochondria
Out
Oxaloacetate
Oxaloacetate
Malate
mitochondria
Malate
oxalozcetate
In mitochondria
Aspartate
Aapartate oxaloacetate
目录
PEP
cytoplasma
GDP + CO2
PEP-carboxykinase
GTP
oxaloacetate
Aspartate
Aspartate
Malate
Malate
NAD+
α-ketoglutarate
NADH + H+
glutamate
oxaloacetate
ADP + Pi
mitocondria
pyruvic
ATP + CO2 carboxylase
Pyruvate
Pyruvate
目录

The resource of NADH+H+ in glyconeogenesis:
The generation of glyceraldehyde-3-phosphate
from 1,3-bisphosphoglycerate need NADH+H+ in
glyconeogenesis.
NADH+H+ is provide from latate when the latate is
the resource of glyconeogenesis.
LDH
Latate
NAD+
pyruvate
NADH+H+
目录
If amino amid is the resource of glyconeogenesis,
NADH+H+ come from mitochondria where NADH+H+
are derived from β- oxadation of fatty acid or TAC. The
transport of NADH+H+ dependent on the conversion of
oxaloacetate and malate.
oxaloac
etate
Malate
NADH+H+ NAD+
mitochondria
Malate
oxaloac
etate
NAD+ NADH+H+
cytoplasma
目录
2. Conversion of Fructose 1,6-Bisphosphate to
Fructose 6-Phosphate
Pi
Fructose 1,6Bisphosphate
Fructose 6Phosphate
fructose 1,6bisphosphatase
(FBPase-1)
3. Conversion of Glucose 6-Phosphate to Glucose
Pi
Glucose 6-Phosphate
Glucose
glucose 6-phosphatase
目录
A set of forward and reverse reactions
catalyzed by different enzymes are called
substrate cycle. If the two kinds of enzyme
activity is equal, the results of the cycle are that
ATP energy is depleted, heat is produced and
no net substrate-to-product conversion is
achieved, so it is also called futile cycle. The
two-enzyme cycle thus provides a means of
controlling the direction of net metabolite flow.

目录
glucose 6-phosphatase
Pi
Glucose 6-Phosphate
ADP
Glucose
hexokinase ATP
FBPase-1
Pi
Fructose 1,6-Bisphosphate
ADP
ATP
PFK-1
ADP+Pi
pyruvic carboxylase
CO2+ATP
Fructose 6-Phosphate
GTP
PEP-carboxykinase
oxaloacetate
Pyruvate
ADP
PEP
Pyruvate kinase
GDP+Pi
+CO2
ATP
目录

The non-carbs substances enter the
gluconeogenesis
The substances of gluconeogenesis is converted to the
intermediate products of carbohydrates metabolism.
-NH2
Glucogenic amino acid
α-oxoacid
Glycerine
lactate
αphosphoglycerol
2H
Phospho
dihydroxyacetone
Pyruvate
 Above intermediate products enter the gluconeogenesis
pathway and generate to glucose or glycogen.
目录
Question about TAC
The intermediate products of TAC performed
as a catalyst without change of it’s quantity.
Oxaloacetate or other intermediate products can
neither be synthesized directly from Acetyl-CoA,
nor be oxidized directly to CO2 and H2O in TAC.
目录
2. Glycolysis and Gluconeogenesis Are Regulated
Reciprocally through two substrate cycle.
 Glycolysis and gluconeogenesis are the two metabolic
pathways in opposite direction. If the gluconeogenesis
from pyruvate is carried out effectively, the glycosis
must be inhibited. And vice versa.
 This coordination is dependent on the regulation of
the two substrate cycle in pathway.
目录
1. The first substrate cycle: between fructose-6-phosphate
and Fructose 1,6-bisphosphate
Pi
Frustose-6phospherate
fructose 2,6bisphosphate
ATP
PFK-1
FBPase-1
AMP
ADP
Fructose 1,6bisphosphate
目录
2. The second substrate cycle: between PEP and pyruvate
PEP
Fructose 1,6bisphosphate
ADP
Pyruvate kinase
oxaloacetate
alanine
ATP
Pyruvate
Acetyl-CoA
目录
3. The physiological significance of gluconeogenesis
is to maintain the stable of blood glucose.
1. The main function of gluconeogenesis:
maintain the stable of blood glucose
 The maintenance of stable blood glucose is dependent on the
gluconeogenesis from amino acid, glycerine when fasting or
starvation.
 Under normal conditions, brain utilized energy derived from
glucose because brain cells could not take energy from fatty acid;
erythrocytes get the energy through glycolysis totally in the
absence of mitochondria; and, bone marrow, nerves tissure are
used to take glycolysis because of their active metabolism. Above
mentioned glucose are generated through the gluconeogenesis.
目录
 The
substrate of gluconeogenesis are lactate,
amino acid and glycerine.
 Lactate come from the muscle glycogenolysis related
with exercise intensity.
 Amino acid and glycerine are the substrate of
gluconeogenesis when in hungry.
目录
2. Gluconeogenesis is an important pathway to
replenish and restore the storage of liver glycogen
C3 pathway: After meal, most glucose is broken
down to lactate or pyruvate which contain three
carbons outside the liver cells, then these C3
substrates enter the liver cells and generate to
glucogen by gluconeogenesis.
目录
3. The enhance of renal gluconeogenesis is helpful to
the maintenance of acid-base balance
 Under long-term fasting and starve conditins, the renal
gluconeogenesis is enhanced which is helpful to the
maintenance of acid-base balance.
 The reason of this change maybe the metabolic acidosis:
pH↓→ PEP-carboxykinase↑→Gluconeogenesis↑
After α–ketoglutarate is consumed in glycolysis, the
deamination of glutamine and glutamic acid will be
enhanced. NH3 in renal tubular cells are excreted and
bound with H+ in urine to decrease the H+. This is good for
the excreting of H+ and retention of Na+ to protect from
acidosis.
目录
4. Lactate cycle:
 In muscle lactate can by produced by glycolysis.
Gluconeogenic capacity of muscle is very low, so lactate
diffused into blood and transported to the liver. In the liver,
glucose is synthesized from lactate by gluconeogenesis. After
glucose is released into blood, it can be taken up by muscle,
which formed a cycle named Lactate cycle or Cori cycle.
 Because the enzymes in the liver and muscle are different,
they could contribute to the formation of lactate cycle.
目录
Lactate
Glucose
cycle (Cori cycle)
Glucose
gluconeo
genesis
glycolysis
Pyruvate
Pyruvate
NADH
NADH
NAD+
Lactate
Lactate
NAD+
Lactate
Blood
muscle
】【
Low gluconeogenesis
Without G-6-P
Liver
【
glucose/mus
cle glycogen
Active gluconeogenesis
With G-6-P
】
目录

Lactate cycle consumes energy:
 6 ATP are needed when 2 lactate are generated to 1
glucose.

Significance:
 Avoid waste of lactate
 Protect from acidosis caused by accumulation of
lactate
目录
Part VII
Metabolism of Other Monose
目录
 Fructose, galactose and mannose enter the
glycolysis through converting into
intermediate products of glycolytic pathway.
目录
Part VIII
The Definition, Level and
Regulation of Blood Glucose
目录
 The definition and level of blood glucose
Blood glucose: the glucose in the blood
The level of blood glucose:
Normal blood glucose ：3.89~6.11mmol/L
目录
 The
physiological significance of the
maintenance of blood glucose level
Ensure the energy supply of some important organs, especially
the organs which is dependent on glucose energy supply.
 The brain depend on glucose because they cannot oxidize
alternative fuels.
 Erythrocytes depend on glycolysis because they have no
mitochondria.
 Bone marrow and nerve tissue are used to utilized glucose
because their active metabolism.
目录
1. The resource and outlet of blood glucose is
relative balanced.
Food carbs
Digestion/
absorption
CO2 + H2O
oxidation,
lysis
Glycogen synthesis
lysis
Liver
glycogen
Blood
glucose
liver(muscle) glycogen
Pentose phosphate pathway
Other carbs
gluconeogenesis
Anabolism of fat, amino acid
Non-carbohydrate substrate
Fat, amino acid
目录
2. The level of blood glucose is mainly regulated
by hormone
 The maintenance of stable levels of glucose in the
blood is one of the most finely regulated homeostatic
mechanisms that involves the liver, extrahepatic
tissues, and several hormones.
 Different metabolic pathways among different
organs could be regulated coordinately to meet the
variable needs of body, it depend on the regulation
of hormone.
 The key enzymes involved in glucose metabolisms
are regulated by different kinds of hormone.
目录
The hormones
regulate blood
glucose
Decrease blood glucose：insulin
Increase blood
glucose：
glucagon
glucocorticoids
epinephrine
目录
1. Insulin is the only hormone which can
decrease blood glucose.
 Insulin is the only hormone which can decrease blood
glucose and promote synthesis of glycogen, lipids, and
proteins.
 Insulin is released in response to hyperglycemia.
目录

Mechanism of insulin
① Insulin enhance glucose transport into adipose tissue and muscle
by recruitment of glucose transporters from the interior of the
cells to the plasma membrane.
② Insulin reduces the cAMP level in the liver by activating a cAMPdegrading phosphodiesterase. By stimulating the glucoseconsuming pathways and inhibiting the glucose-producing
pathways in the liver, insulin lower the blood glucose level.
③ Insulin activate pyruvate dehydrogenase by activating pyruvate
dehydrogenase phosphatase, to accelerate oxidation of pyruvate to
Acetyl-CoA, resulting the aerobic oxidation of carbohydrates.
④ Insulin inhibit gluconeogenesis in liver by decreasing the synthesis
of PEP-carboxykinase and promoting the entrance of amino acid
into muscle and protein synthesis.
⑤ Insulin slow the speed of fat mobilization through inhibiting the
hormone-sensitive lipase in fat.
目录
2. Different hormone increase blood
glucose under different conditions.
1．Glucagon is the main hormone which increase
blood glucose in vivo.
Glucagon is released in response to hypoglycemia or
high level of amino acid in blood.
目录

Mechanism of glucagon
目录
Insulin and glucagon not only regulate blood
glucose, but also play important role on the metabolism
regulation of three nutriments.
The change of carbohydrates, fat and amino acid
metabolism is decided by the insulin/glucagon ratio.
The secretion of two hormones is opposite.
e.g. hyperglycemia stimulate the release of insulin,
but inhibit the release of glucagon.
目录
2. Glucocorticoids cause the increase of blood glucose

Mechanism of glucocorticoids
① They can increase gluconeogenesis by enhancing
hepatic uptake of amino acids and increasing
activity of aminotransferases and key enzymes of
gluconeogenesis.
② They inhibit the uptake and utilization of glucose in
extrahepatic tissues.
目录
3. Epinephrine is stress hormone that increase
blood glucose

Mechanism of epinephrine
Epinephrine is secreted as a result of stress stimuli
and lead to glycogenolysis in the liver and muscle owing
to stimulation of phosphorylase via generation of cAMP.
目录
3. Dysfunction of carbohydrate metabolism:
abnormal blood glucose and diabetes.
Under normal conditions, there are a fine
mechanism for the regulation of glucose
metabolism to keep blood glucose from large
fluctuations and sustained increase after
uptake a large glucose.
A healthy individual could tolerate to
the uptake of a large glucose and keep blood
glucose in normal level, this is called glucose
tolerance.
目录
 Two
common symptoms of carbohydrate
metabolism disorder in clinical:
 Hypoglycemia
 Hyperglycemia
目录
1.
Hypoglycemia: blood glucose concentration
below 3.0mmol/L
 Hazards
of hypoglycemia:
Hypoglycemia influence the function of brain
because brain cells depend on the oxidation of glucose to
supply energy. Hypoglycemia causes symptoms such as
dizziness or light-headedness, weakness, palmus even faint
which is called hypoglycemic shock. It can lead to death if
we do not give the patient intravenous glucose supplement.
目录
 The
reasons of hypoglycemia:
① Dysfunction of pancreas: hyperfunction
of pancreas β-cell, hypofunction of
pancreas α-cells;
②
Dysfunction
of
liver:
liver
cancer,
glycogen storage disease;
③
Dyscrinism: hypofunction of Pituitary,
hypofunction of adrenal cortex;
④
Tumor: stomach cancer;
⑤
Fasting and starve;
目录
2. hyperglycemia: fasting blood glucose exceed
6.9mmol/L
 In clinical, fasting blood glucose exceed 5.6 ～
6.9mmol/L is called hyperglycemia.
 When blood glucose concentration exceed the tubular
reabsorption capacity (renal glucose threshold),
hyperglycemia caused glucosuria.
 Persistence hyperglycemia and glucosuria, especially
fasting blood glucose and glucose-tolerance are higher
than the normal range, it is often caused by diabetes
mellitus.
目录

The reasons of hyperglycemia：
①
Diabetes;
②
Genetic defects in insulin receptor;
③
chronic nephritis, nephrotic syndrome
④
Physiological hyperglycemia and glucosuria;
目录
3. Diabetes is a common disease of
carbohydrate metabolism disorder
Diabetes, caused by a deficiency in the
secretion or action of insulin, is a relatively
common disease.
目录
 Two
types of diabetes:
Type Ⅰ
(insulin-dependent )
Type Ⅱ
(non-insulin-dependent )
目录
Problems:
1.The process of glutamate completely oxidized into CO2 and
H2O and the ATP ?
2.Which metabolism pathway that G-6P could enter in liver or
muscle?
G（replenish blood glucose）
6-Phosphoglucono-lactone
（enter pentose phosphate
pathway）
G-6-P
F-6-P
（enter glycolysis）
G-1-P
UDPG
Gn（Glycogen synthesis）
目录