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Chapter 4

Carbohydrate Metabolism

Weihong Hou

Deer derive energy from carbohydrate


(cellulose) in the plants it consumes.
The functions of carbohydrate
1. The major function of carbohydrate
is as a fuel to be oxidized and provide
energy for other metabolic processes.
Carbohydrate is the “staple food” for
most organisms. Sugar and starch
represent the major part of total caloric
intake for humans.
Glucose, the hydrolyzed product of
starch mainly, is an important and
common fuel. In mammals, glucose is
the only fuel that the brain uses under
non-starvation conditions and the only
fuel that red blood cells can use at all.
When 1 gram of carbohydrate is
oxidized completely to CO2 and H2O, 4
kilocalories (66.8 kilo joule, kJ) of
energy can be released.

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

GLUCOSE G-6-P 6-phosphogluconate

Pi Pentose phosphate pathway


Fructose 6-p
Anaerobic degradation
(glycolysis) non-carbohydrates
trioses phosphate Gluconeogenesis
The formation of glucose
energy
pyruvate from non-carbohydrates
Glycolytic pathway
lactate
acetyl CoA
Formation of acetyl CoA

Aerobic Tricarboxylic acid cycle


oxidation
CO2 + H2O + energy
end Oxidative phosphorylation
Section I Glycolysis
(Anaerobic Degradation)
This pathway is universal pathway, an ancient pathway, may
occur in all human cells. The complete glycolytic pathway was
elucidated by 1940, largely through the pioneering contributions
of Gustav Embden, Otto Meyerhof, Carl Neuberg, Jacob Parnas,
Otto Warburg, Gerty Cori, and Carl Cori. Glycolysis is also
known as the Embden-Meyerhof pathway.

“Glycolysis” is derived from


Greek words glycos (sugar,
sweet) and lysis (dissolution)

The bivalve mytilus These mussels, inhabitants


of the intertidal zone, display habitat-dependent
anaerobiosis.
2. Another function of carbohydrate is as the structural
elements in cell coat or connective tissues.
1).Glycoconjugates including glycoprotein, proteoglycan, and
glycolipid have special functions,
such as
Protection (blood coagulation factors, immunoglobulin,
glycosaminoglycan [as lubricant to lubricate skeletal
joints]);
Regulation (some hormones, some enzymes);
Transportation (lipoprotein, transferrin);
Receptors (some glycosyl chains of glycoconjugate extend
on the surface of plasma membrane as antennae to form
so called glycocalyx, to have the function of recognition,
adhesion, and signal transduction).
2). Component of nucleic acids
3). Conversion to lipids and non-essential amino acids
1. Basic process of glycolysis
1-1 The degradation of glucose to triose phosphate
1-2 Conversion of triose phosphate to pyruvate
1-3 Conversion of pyruvate to lactate

Triose phosphate
Dihydroxyacetone phosphate
glucose Fructose 1,6-bisphosphate

phosphorylation Glyceraldehyde 3-phosphate

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 lactate COOH phosphofructokinase PFK


dehydrogenase Mg2+
CHOH ADP
pyruvate c=o
CH3 CH3 CH2O P
+
NAD lactate
+ CH2O P
NADH+H O

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

• Glycolysis is the emergency energy-yielding pathway, such as


run 100-meters dash, climb a mountain, standing high jump.
•. 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 clinical practice,
such as heart failure,
circulation failure,
respiration failure,
excessive loss of blood.
Liu Xiang, a Chinese young sportsman, was the first oriental who won
the golden medal in the 110meter hurdles at the Olympic Games
Section II 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.
1. The basic process of aerobic oxidation of glucose
Glucose oxidation can be divided into 3 phases:
a. Oxidation from glucose to pyruvate in cytosol
b. Oxidation from pyruvate to acetyl CoA in mitochondria
c. Tricarboxylic acid cycle and oxidative phosphorylation

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+

Pyruvate dehydrogenase complex of mammals including

pyruvate dehydrogenase (20 or 30 chains)


dihydrolipoyl transacetylase (60 chains)
dihydrolipoyl dehydrogenase (6 chains)
TPP, NAD+, FAD, CoA, Lipoic acid,
(a) (b) (c)

(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

oxidized lipoamide S CH3 C H S


S 1 FAD
(E1) TPP
CO2
TPP
FAD
E1 E2 E3
E1 E2 E3
hydroxyethyl TPP
2
NADH+H+ (E2)
5 (E3) O HS
acetyl lipoamide
oxidized lipoamide H3C C S
NAD+ S FAD
TPP
S E1 E2 E3
TPP FADH2
E1 E 2 E3 3
dihydrolipoamide CoASH
HS (E2)
4 (E3) HS
O
TPP FAD H3C C¡« SCoA
E1:pyruvate dehydrogenase
E2:dihydrolipoamide transacetylase
E1 E2 E3 acetyl CoA
E3:dihydrolipoamide dehydrogenase
Pyruvate+NAD++HSCoA Acetyl CoA+NADH+H++CO2
end
1-3 Tricarboxylic acid cycle

Roundabouts,or traffic circles, function as hubs to facilitate traffic flow.


The tricarboxylic acid cycle 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.
O

~
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

CH2 COOH CH2 CH2


succinate O C ~ SCoA CO2 O C COOH
CoASH
GTP GDP+Pi succinyl CoA CoASH α -ketoglutarate
alpha-ketoglutarate
end dehydrogenase complex
ADP ATP
Tricarboxylic acid cycle is also named Krebs
cycle for the memory of the discover Hans Krebs.

Hans Krebs was one of the great pioneers of


modern biochemistry. He was born in Germany
and received his medical education there. In 1932,
when he was an assistant in medicine, he worked
out the urea cycle with Kurt Henseleit, a medical
student.
In 1937, he discovered "tricarboxylic acid
cycle" in England by himself.
From 1954 on he was the head of the
Department of Biochemistry at Oxford. He was
retired from that position in 1967. He was still
working actively until his death in 1981.
The "tricarboxylic acid cycle" has been
regarded as the most important single discovery
in the history of metabolic biochemistry.
Table III-1 generation of ATP in aerobic oxidation of glucose
Reactions Moles of ATP
pathway Methods of
Catalyzed by formed per mol
ATP production
of glucose

Glycolytic Glyceraldehyde 3-phosphate


dehydrogenase Respiratory chain Oxidation of 2 NADH 5 or 3
pathway
Phosphoglycerate kinase Phosphorylation at substrate level 2
Pyruvate kinase Phosphorylation at substrate level 2
Allow for consumption of ATP by reactions catalyzed by hexokinase and phosphofructokinase -2
Production of Pyruvate dehydrogenase Respiratory chain Oxidation
acetyl CoA complex 5
of 2 NADH
Tricarboxylic Isocitrate dehydrogenase Respiratory chain Oxidation of 2 NADH 5
acid cycle Alpha-ketoglutarate
Respiratory chain Oxidation of 2 NADH 5
Dehydrogenase complex
Succinyl CoA synthetase Phosphorylation at substrate level 2
Succinate dehydrogenase Respiratory chain Oxidation of 2 FADH2 3
Malate dehydrogenase Respiratory chain Oxidation of 2 NADH 5
Total per mole of glucose under aerobic conditions: 32 or 30 ATPs
2.The regulation of aerobic oxidation
1.1 Regulation of pyruvate dehydrogenase complex

pyruvate acetyl CoA


NAD+,CoA NADH+H+, CO2

Pyruvate dehydrogenase AMP,CoA


acetyl CoA,NADH
(active form) NAD+, Ca2+
ATP,FA
ATP Pi
pyruvate dehydrogenase pyruvate dehydrogenase
kinase phosphatase
ADP H2O

ADP,NAD+ Pyruvate dehydrogenase insulin,Ca2+


(inactive form)

Allosteric regulation and covalent modification


2.2 Regulation of tricarboxylic acid cycle

[NADH]/[NAD+]
[ATP]/[ADP]

The activity of tricarboxylic


acid cycle is inhibited
Section I I I The Pentose Phosphate Pathway (PPP)
1. The basic process:
Oxidative phase (formation of pentose phosphate)
Non-oxidative phase (group transferring)
H2O
NADP+ NADPH+H +
CH2O P CH2O P CH2O P
O O OH
O COOH
G-6-P lactonase
dehydrogenase 6-P-gluconolactone 6-P-gluconate
G-6-P
CO2 NADP+

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

3) NADPH serves as the coenzyme of mixed function oxidases (mono-


oxygenases). Biotransformation.
end
Deficiencies of certain enzymes
of the PPP are major causes of
hemolysis of red blood cells,
resulting in one type of hemolytic
anemia. There are 100 million
people in the world suffering the
deficiency of glucose 6-
phosphate dehydrogenase. When
the susceptible people take some
medicine such as antimalarial
primaquine, aspirin, or
sulfonamide, or eat broad bean
(fava bean), hemolysis can be
manifested. People may suffer
from jaundice
Vicia faba. The Mediterranean plant
Vicia faba is a source of fava beans that
contain the purine glycoside vicine.
Section IV glycogen Formation and Degradation

Glycogen granules hepatocyte


α 1→4 glucosidic bond

High solubility and more reactive points


for synthesis and degradation
2Pi
1. GLYCOGENESIS UTP
(uridine H2O glycogen
triphosphate) PPi UDP
phospho primer branching
ATP ADP
Mg2+ glucomutase enzyme
glucose G-6-P G-1-P UDPG glycogen glycogen
GK(liver),HK (uridine GLYCOGEN ¦Á-1,4-glycosidic ¦Á-1,4,¦Á-1,6-
diphosphate SYNTHASE bond glycosidic bond
glucose) Pi
debranching
glucose 6-phosphatase
enzyme
(liver)
PHOSPHORYLASE

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

phosphorylase a 14 glucose 1-phosphate


glucan transferase

glucosidase

Debranching has two enzyme


activities in one peptide: oligo α 1 glucose
-1,4 α 1,4-glucantransferase andα
1,6-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

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 V Gluconeogenesis
The process of transformation of non-carbohydrates to
glucose or glycogen is termed as gluconeogenesis.
1. The basic process of gluconeogenesis
Essentially a reversal of glycolysis with three barriers
circumvented by four additional enzymes:
Glc G-6-P F-6-P F-1,6BP GAP 1,3-BPG 3-PG 2PG PEP
Oxaloacetate
DHAP
Lactate Pyruvate

1) from pyruvate to phosphoenolpyruvate:


pyruvate carboxylase
phosphoenol pyruvate carboxykinase
2) from fructose 1,6-phosphate to fructose 6-phosphate
fructose 1,6-bisphosphatase
3) from glucose 6-phosphate to glucose
glucose 6-phosphatase
1-1 The conversion of pyruvate to phosphoenol pyruvate

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

glucose 6-phosphate glucose


glucose 6-
phosphatase

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

lactate pyruvate pyruvate


end
2. The significance of gluconeogenesis

2-1 To keep blood sugar level stable


Gluconeogenesis meets the demands of the body for glucose
when carbohydrate is not available in sufficient amount from the
diet.
For a person each day
brain spent 125g of glucose
renal medulla
erythrocytes 50g
retina
skeletal muscle 50g

The liver is only able to deposit about 100-150g of glucose


as the form of glycogen. More than 25% of glucose is supplied
by gluconeogenesis.
2-2 To replenish liver glycogen

2-3 To regulate acid-base balance

phosphoenolpyruvate carboxykinase
gluconeogenesis induces biosynthesis

alpha-ketoglutarate glucose H+

NH3 H+

glutamic acid NH4+

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.

2-5 To convert glucogenic amino acids to glucose.

3. Cori cycle

glucose glucose glucose

gluconeogenesis glycolytic pathway

pyruvate pyruvate
+
NADH+H+
NAD
+ NAD+
NADH+H
lactate lactate lactate

liver BLOOD muscle


4.Regulation of gluconeogenesis and glycolysis
F-6-P
ATP
citrate
F-1,6-biphosphatase ADP phosphofructokinase-1
AMP
F-2,6-BP
F-1,6-BP
F-1,6-BP
insulin gluconeogenesis
glycolysis

glucokinase pyruvate carboxylase


phosphoenolpyruvate carboxykinase
phosphofructokinase-1
pyruvate kinase fructose 1,6-biphosphatase
glucose 6-phosphatase

end
glucagon Glucocorticoids
epinephrine
Section VI Blood Sugar and Its Regulation

origin (income) fate (outcome)

aerobic oxidation
dietary supply CO2 + H2O + energy

liver glycogen Blood sugar glycogenesis


glycogen
non-carbohydrate 3.89~6.11mmol/L PPP etc
(gluconeogenesis) other saccharides
other saccharides non-carbohydrates
(lipids and some amino acids)

>8.89¡« 10.00mmol/L
(threshold of kidney)

urine glucose

end
The Metabolic Changes on High Blood Sugar Level

High blood sugar level


(hyperglycemia)

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

Low blood sugar level


(hypoglycemia)

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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