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Carbohydrate Metabolism
Weihong Hou
The superstock
Overview of carbohydrate metabolism
GLYCOGEN
Glycogenesis Glycogenolysis
The storage of glucose UDPG The release of glucose
in the form of glycogen Pi from its storage form
for later use. for use by cells
G-1-P
Triose phosphate
Dihydroxyacetone phosphate
glucose Fructose 1,6-bisphosphate
ATP production
Lactate Pyruvate
reduction
GLYCOLYSIS O
CH2O P O-
ATP AD P CH2O P
CH2OH O-
2+ CH2OH
O Mg O O
Hexokinase(HK) isomerase
glucose glucokinase(GK) G-6-P
fructose 6-phosphate ATP
COOH
fructose 1,6-bisphosphate
Pyruvate (enol) COH
CH2OH
CH2 aldolase
C O
ATP
Substrate level pyruvate kinase
CHO
isomeraseCH2O P
phosphorylation ADP
CHOH dihyroxy
COOH CH2O P acetone
Energy redistribution glyceraldehyde phosphate
CO¡« P 3-phosphate
CH2 within molecules NAD+ H3PO4
phosphoenol glyderaldehyde
pyruvate NADH+H+ 3-phosphate
enolase dehydrogenase
COOH COOH COO¡« P
ATP ADP
H2O
CHO P CHOH CHOH Energy redistribution
mutase Phosphoglycerate
CH2OH CH2O P
kinase
CH2O P within molecules
glycerate glycerate glycerate
2-phosphate 3-phosphate 1,3-bisphosphate
end Substrate level
phosphorylation
CH2OH ATP ADP CH2O P
O 2+ O
Mg
hexokinase(HK)
glucokinase(GK,liver)
glucose glucose 6-phosphate
4 points for this reaction:
1. Glucose as the form of glucose 6-phosphate is captured within
cells,the phosphate ester can not penetrate the membrane.
2. The investor of this reaction is ATP, which as a phosphate donor
provides energy to the reaction. Energy-consuming reaction and
irreversible reaction.
3. HK is a key enzyme,can be inhibited by its product G-6-P, and
has a high affinity (Km= 0.1mmol/L) for its substrate.
4. Glucokinase (GK) is the isoenzyme IV, present in liver. This
enzyme has a higher Km (∼ 10mmol/L) for its substrate.
Vm
Hexokinase
Concentration of blood sugar
fluctuates at 3∼ 9 mmol/L which
does not affect the velocity of
the enzymatic reaction.
Km=0.1mmol/L Blood sugar
0 0.1 2 3 4 5
V
Glucokinase
Concentration of blood sugar
fluctuates at 3∼ 9 mmol/L which
actually affects the velocity of
Blood sugar the enzymatic reaction.
0 2 4 6 8 10 12 14 16 18
Km=about 10mmol/L
Turn back
A summary
a. Location: cytosol
b. Original material: glucose
c. End product:lactate
d. Key enzymes: Hexokinase (HK)
Phosphofructokinase 1 (PFK-1)
Pyruvate kinase (PK)
a. Twice energy redistributions within molecule.
Twice substrate level phosphorylations, net amounts of
ATP produced are 2.
a. Once dehydrogenation: oxidation
Once hydrogenation: reduction
2. The regulation of glycolysis Hormone regulation
Covalent regulation
ATP
Glucagon ⊕ Adenylate AMP Citrate
Allosteric regulation
cyclase
cAMP
⊕
Glucose ATP ⊕ ADP
PFK-2 FBP-2
Glucose 6-phosphate active inactive
ATP
F-6-P PKA Phosphoprotein F-2,6-BP
Phosphatase
ADP Pi
P P
PFK-2 FBP-2
glycolysis ATP inactive active
PFK-1 ⊕ Pi
⊕
ADP end
⊕ ⊕
Lactate F-1,6-BP AMP Citrate
Next
3. The significance of glycolysis
O2 O2 O2 H 2O
Acetyl CoA H+ +e
CO2
Glucose G-6-P Pyruvate Pyruvate
Tricarboxylic acid cycle
cytosol mitochondria
1-1 The oxidation of glucose to pyruvate
1-2 Pyruvate oxidative carboxylation
Mg2+
(a) Electron micrograph of the pyruvate dehydrogenase complex isolated from E.coli,
showing its subunit structure.
(b) In terpretive model of the enzyme from E. coli. Transacetylase (24 peptides) forms
the cube-like core of the complex, pyruvate dehydrogenase (12 dimers) is
distributed on the 12 edges of the cube, dihydrolipoyl dehydrogenase (6 dimers) on
the six faces of the cube.
(c) Interpretive model of the organization of the mammalian pyruvate dehydrogenase
complex.
O O
H3C C C OH Pyruvate dehydrogenase complex
pyruvate
OH S
~
CH2 COOH
O C COOH CH3 CSCoACoASH HO C COOH H2O
acetyl CoA CH2 COOH
CH2 COOH CH2 COOH
C COOH
citrate synthase aconitase CH COOH
oxaloacetate H2O citrate
NADH+H+ cis-aconitate
+
malate dehydrogenase H2O
NAD
HO CH COOH The first reaction in TCAC is the aconitase
CH2 COOH condensation of acetyl-CoA and
malate oxaloacetate to form citrate. The CH2 COOH
fumarase TCAC is also named citrate cycle. HC COOH
H2O
HC COOH Tricarboxylic HO CH COOH
isocitrate
HOOC CH
fumarate Acid Cycle NAD
+
FADH2 isocitrate dehydrogenase
succinate dehydrogenase NADH+H+
FAD succinyl CoA NADH+H+ NAD
+ CO2
CH2 COOH syntetase CH2 COOH CH2 COOH
[NADH]/[NAD+]
[ATP]/[ADP]
6-P-gluconate
CH2OH
dehydrogenase
transketolase C=O
transaldolase CHOH
glycolysis NADPH+H+
CHOH
CH2O P
ribulose 5-phosphate
Location: cytosol
Original material: glucose 6-phosphate
End product: the intermediate products of glycolysis
The coenzyme of dehydrogenation: NADP+
CH2OH
CH2OH CHOH
C=O
C=O CHOH
4
CHOH HO CH CH2OPO32-
CHOH CHOH 5 glyceraldehyde
CH2OPO32- CH2OPO32- 3-phosphate CH2OH
ribulose 5-phosphate xylulose 5-phosphate
CH2OH C=O
CHO
C=O HO CH
NADPH+H+ CO2 4' CHOH
HO CH CHOH
3 CHOH 6
NADP+
2- CHOH CHOH
O3-POCH2 CHOH
OH CHOH CH2OP32-
4 CH2OPO3 2-
COOH CHOH
ribose 5-phosphate fructose
CH2OPO32- 6-phosphate
6-phosphogluconate sedoheptulose
CH2OH
2 C=O 7-phosphate
2- H2O HO CH CHO
O3-POCH2
O CHOH CHOH
O 2-
CH2OPO3 CHOH
xylulose 5-phosphate CH2OPO32-
6-phosphogluconolactone erythrose
+
NADPH+H 4-phosphate glycolysis
7
CH2OH
1
NADP + CHO C=O
2-
O3-POCH2 CHOH HO CH
O
CH2OPO32- CHOH
CHOH
glyceraldehyde
3-phosphate CH2OP32-
end G-6-P
fructose
6-phosphate
1. G-6-P dehydrogenase, 2. gluconolactone hydrolase, 3. 6-phosphogluconate
Pentose Phosphate Pathway dehydrogenase, 4. epimerase, 4'.isomerase, 5. 7. transketolase, 6. transaldolase
2. The significance of PPP
2-1 Ribose 5-phosphate
2-2 NADPH
1) Reducing power for biosynthesis of fatty acids, cholesterol, and so on.
2) Coenzyme of glutathione reductase to keep the normal level of reduced
glutathione.
NADPH+H+ NADP+
Glutathione reductase
G-S-S-G 2 GSH
2 H2O H2O2
MHb Hb
2. GLYCOGENOLYSIS O
NH O
CH2OH
O
O O O O N O PPi NH
CH2OH
O P + -O P O P O P O CH2 O O N O
O- O O
O- H H
G-1-P O- O- O- UDPG pyro- O P O P O CH2 O
H
OH OH phosphorylase
UTP O- O- H H
H
UDPG OH OH
CH2OH
CH2OH CH2OH UDP CH2OH CH2OH CH2OH
O O O
+ O O O
O-UDP O O
O O O
GLYCOGEN
UDPG glycogen primer (n) SYNTHASE glycogen (n+1)
end
Glycogenesis
glycogen synthase
©–©–©–©–©–©–©–©–©–©–©–
oligo¦Á-1,4 ¦Á-1,6-glucantransferase
(Branching enzyme)
©–©–©–©–©–©–©–
©–©–©–©–
glycogen synthase
©–©–©–©–©–©–©–©–©–©–©–©–
©–©–©–©–©–©–©–©–©–©–©–
©–©–©–©–©–©–©–©– oligo¦Á-1,4 ¦Á-1,6-glucantransferase
©–©–©–©–©–©–©–©–©–©–©–©–
end ©–©–©–©–©–©–©–©–©–©–©–©–
phosphorylase a
Glycogenolysis
glucosidase
phosphorylase a
12 glucose 1-phosphate
end
3. Regulation of hormons:glucagon, epinephrine
Glycogenesis and active inactive
Glycogenolysis adenylate adenylate
cyclase cyclase
ATP cAMP
ATP phosphorylase b kinase Pi
inactive active
protein protein
P
kinase A kinase A
ADP phosphorylase b kinase H2O
ATP ADP
ATP ADP
P
P phosphorylase b phosphorylase a
glycogen glycogen
synthase synthase
(active) (inactive) Pi H2O
glycogenolysis
Pi H2O protein
glycogenesis phosphatase-1
inhibitor-1 inhibitor-1 P
end (inactive) ATP (active)
4. The significance of
glycogenesis and glycogenolysis
glycolysis
ATP ADP
PK
CH3 CH3
C O pyruvate C O¡« P
COOH CH2 phosphoenol pyruvate
pyruvate
ATP carboxylase GDP
(in Mt)
CO2 COOH CO2
biotin phosphoenol pyruvate
CH2 carboxykinase (1/3 in Mt, 2/3 in Cytosol)
ADP + Pi C O GTP
O
COOH
oxaloacetate C biotin
HN NH
gluconeogenesis
HC HC
H2C HC (CH2)4 COOH
S
1-2 The conversion of fructose 1,6-bisphosphate
to fructose 6-phosphate
glycolysis
ADP ATP
Mg2+
phospho-
fructokinase 1
fructose 1,6-bisphosphate fructose6-phosphate
fructose 1,6-
bisphosphatase
H2O Pi
gluconeogenesis
1-3 The conversion of glucose 6-phosphate to glucose
glycolysis
ADP ATP
Mg2+
glucokinase
liver
H2O Pi
gluconeogenesis
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.
Bumblebee must maintain a thoracic temperature
of about 30°C to fly. A bumblebee is able to maintain
this high thoracic temperature and forage for food
even when the ambient temperature is only 10 °C
because phosphofructokinase and fructose 1,6-
bisphosphatase in its flight muscle are simultaneously
highly active; the continuous hydrolysis of ATP
generates heat. In contrast, the honeybee has almost
no fructose 1,6-bisphosphatase in its flight muscle
and consequently cannot fly when the ambient
temperature is low.
glucose glycogen
UDPG GLUCONEOGENESIS
G-6-P G-1-P
F-6-P
CYTOSOL MITOCHONDRIA
F-1,6BP
glyceral-
dihydroxy- dehyde 3- malic acid malic acid
acetone phosphate
phosphate Glutamate Glutamate NAD+
a-ketoglutarate a-ketoglutarate NADH+H+
1.3-diphospho-
glycerol glycerate oxaloacetate aspartate aspartate oxaloacetate
GTP
2/3 ADP + Pi
glycerate 3-P CO2
GDP
biotin
phosphoenol
glycerate 2-P CO2
pyruvate ATP
phosphoenolpyruvate carboxykinase
gluconeogenesis induces biosynthesis
alpha-ketoglutarate glucose H+
NH3 H+
NH3 NH4+excreted in
urine and pH Na+ absorbed
glutamine raised in blood
urine
2-4 To clear the products of other tissues ’ metabolites from
the blood.
3. Cori cycle
pyruvate pyruvate
+
NADH+H+
NAD
+ NAD+
NADH+H
lactate lactate lactate
end
glucagon Glucocorticoids
epinephrine
Section VI Blood Sugar and Its Regulation
aerobic oxidation
dietary supply CO2 + H2O + energy
>8.89¡« 10.00mmol/L
(threshold of kidney)
urine glucose
end
The Metabolic Changes on High Blood Sugar Level
insulin released
insulin receptor
cAMP
active transport 1
4
in muscle and modulating system 2 gluconeogenesis
adipose tissue 3 5
cells (not in liver 5
and brain) 6 glycogenolysis
2
glycolysis
and aerobic lipogenesis
lipolysis
oxidation
glycogenesis protein
synthesis
end
Metabolic Changes on Low Blood Sugar Level
glucagon
cAMP
1 Modulating system 1
2 hepatic
3 4 3
hepatic glycogenesis
glycogenolysis
glycolysis
gluconeogenesis lipolysis transport of
glucogenic
end amino acids
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