1) Glycolysis breaks down glucose to pyruvate, generating a small amount of ATP. Key enzymes include hexokinase, phosphofructokinase, and pyruvate kinase. 2) Pyruvate is oxidized to acetyl-CoA in mitochondria by the pyruvate dehydrogenase complex, producing NADH. 3) Acetyl-CoA then enters the citric acid cycle, where it is oxidized to carbon dioxide, generating more NADH and FADH2. This fuels the electron transport chain to produce large amounts of ATP through oxidative phosphorylation.

1. Carbohydrates Metabolism

2. § 1 Overview
• Carbohydrates in general are
polyhydroxy aldehydes or
ketones or compounds which
yield these on hydrolysis.

3. Biosignificance of Carbohydrates
• The major source of carbon atoms and
energy for living organisms.
• Supplying a huge array of metabolic
intermediates for biosynthetic reactions.
• The structural elements in cell coat or
connective tissues.

4. Glucose Transporters (GLUT)
A family of glucose transporters (GLUTs)
facilitates transport of D-glucose across the
plasma membrane.
The gene for the GLUT family are
expressed in tissue specific manner.
Glucose transporters designated as
GLUT 1-5 all have 12 transmembrane
segments with a significant amino acid
similarity

5. • Direction of movement of glucose is usually
out to in. Dependent on concentration
gradient however, erythrocyte GLUT-1
facilitates transport in both direction
• The three affinity- transporters (GLUT-1,
GLUT-3, GLUT-4) function at rates close to
maximal velocity because their Km values
are below the normal blood sugar level

6. Isoform Tissue
GLUT1: RBCs, brain - abundant
heart, muscles – low
placenta
GLUT 2: Liver, pancreas,
intestines, kidneys
GLUT 3: Brain, kidneys, placenta
GLUT4: Adipose tissue, muscle, heart
GLUT 5: Spermatozoa, intestine

7. • GLUT 2: catalyzes both glucose influx & efflux
in liver cells; it is involved in sensing blood
glucose level.
• GLUT 4: is an insulin dependant transporter
• GLUT 5: primary transporter of fructose
• Activity of some GLUT, in muscles is stimulated
by exercise & hypoxia

8. The metabolism of glucose
• glycolysis
• aerobic oxidation
• pentose phosphate pathway
• glycogen synthesis and catabolism
• gluconeogenesis

9. glycogen
Glycogenesis Glycogenolysis
Pentose phosphate
pathway
Ribose, NADPH
Glycolysis lactate
H2O+CO2
aerobicoxidation
Digestion
absorption
starch
Lactate,
amino
acids,
glycerol
glucose
Gluconeo-
genesis

10. §2 Glycolysis

11. Glycolysis
• The anaerobic catabolic pathway by
which a molecule of glucose is broken
down into two molecules of lactate.
glucose →2lactic acid (lack of O2)
• All of the enzymes of glycolysis locate
in cytosol.

12. 1. The procedure of glycolysis
G
pyruvate
lactic acid
glycolytic pathway

13. 1) Glycolytic pathway :
G → pyruvate
including 10 reactions.

14. • Phosphorylated G cannot get out of cell
• Hexokinase , HK (4 isoenzymes) ,
glucokinase, GK in liver ;
• Irreversible .
(1) G phosphorylated into glucose 6-phosphate
OH
OH
H
OH
H
OHH
OH
CH2
H
HO
OH
OH
H
OH
H
OHH
OH
CH2
H
OP
ATP ADP
Hexokinase
Mg2+
G G-6-P

15. hexokinase
glucokinase
occurrence in all tissues only in liver
Km value 0.1mmol/L 10mmol/L
Substrate G, fructose, glucose
mannose
Regulation G-6-P Insulin
Comparison of hexokinase and
glucokinase

16. (2) G-6-P → fructose 6-phosphate
OH
OH
H
OH
H
OHH
OH
CH2
H
OP
G-6-P
isomerase OH
CH2OH
H
CH2
OH H
H OH
O
OP
F-6-P

17. (3) F-6-P → fructose 1,6-bisphosphate
• The second phosphorylation
• phosphofructokinase-1, PFK-1
OH
CH2OH
H
CH2
OH H
H OH
O
OP
F-1,6-BP
OH
CH2
H
CH2
OH H
H OH
O
OP O P
ATP ADP
Mg2+
F-6-P
PFK-1

18. (4) F-1,6-BP → 2 Triose phosphates
• Reversible
F-1,6-BP
CH2
C O
C HHO
C OHH
C OHH
CH2
O P
O P
CH2
C O
O P CHO
CHOH
CH2 O PCH2OH
+
aldolase
dihydroxyacetone
phosphate,
DHAP
glyceraldehyde
3-phosphate,
GAP

19. (5) Triose phosphate isomerization
G→2 molecule glyceraldehyde-3-phosphate,
consume 2 ATP .
CH2
C O
O P CHO
CHOH
CH2 O PCH2OH
DHAP GAP
phosphotriose
isomerase

20. (6) Glyceraldehyde 3-phosphate →
glycerate 1,3-bisphosphate
CHO
CHOH
CH2 O P
NAD+
NADH+H +
Pi
glyceraldehyde
3-phosphate
dehydrogenase,
GAPDH
C
CHOH
CH2 O P
O O~ P
glycerate
1,3-bisphosphate,
1,3-BPG
glyceraldehyde
3-phosphate

21. (7) 1,3-BPG → glycerate 3-phosphate
• Substrate level phosphorylation
COO-
CHOH
CH2 O P
C
CHOH
CH2 O P
O O~ P
ADP ATP
glycerate
1,3-bisphosphate
glycerate
3-phosphate
Phosphoglycerate
kinase

22. (8) Glycerate 3-phosphate → glycerate 2-
phosphate
COO-
CHOH
CH2 O P
COO-
CH
CH2OH
O P
glycerate
3-phosphate
glycerate
2-phosphate
Mutase

23. (9) Glycerate 2-phosphate →
phosphoenol pyruvate
COO-
CH
CH2OH
O P
COO-
C
CH2
O
PEP
~ P + H2O
enolase
glycerate
2-phosphate

24. (10) PEP →pyruvate
• Second substrate level phosphorylation
• irreversible
COO-
C
CH3
ADP ATP
COO-
C
CH2
O
PEP
~ P
pyruvate kinase
O
Pyruvate

25. 2) Pyruvate → lactate
COO
C
CH3
NAD+NADH + H+
O
Pyr
COO
CHOH
CH3
Lactate dehydrogenase,
LDH
Lactic acid

26. Summary of Glycolysis
ATP
ADP
Mg2+
PFK-1
GAP DHAP
glycerate
1,3-bisphosphate
NADH+H+
glyceraldehyde
3-phosphate
dehydrogenase
H3PO4
NADH+H+
NAD+
ADP
ATP
glycerate
3-phosphate
glycerate
2-phosphate
H2O
PEP
ATP
ADP
pyruvate kinase
lactate
pyruvate
G G-6-P F- 6-P F- 1,6-BP
NAD+
Phosphoglycerate
kinase
Isomerase
Aldolase
Mutase
Enolase
LDH
HK
ATP
ADP
Mg2+

27. Total reaction:
C6H12O6 + 2ADP + 2Pi
2CH3CHOHCOOH + 2ATP + 2H2O
Formation of ATP:
The net yield is 2 ~P or 2 molecules of
ATP per glucose.

28. 2. Regulation of Glycolysis
• Three key enzymes catalyze
irreversible reactions : Hexokinase,
Phosphofructokinase & Pyruvate
Kinase.

29. 1) Hexokinase and glucokinase
• This enzyme is regulated by covalent
modification, allosteric regulation and
isoenzyme regulation.
• Inhibited by its product G-6-P.
• Insulin induces synthesis of
glucokinase.

30. 2) PFK-1
The reaction catalyzed by PFK-1 is
usually the rate-limiting step of the
Glycolysis pathway.
This enzyme is regulated by covalent
modification, allosteric regulation.

31. bifunctional
enzyme

32. 3) Pyruvate kinase
• Allosteric regulation:
F-1,6-BP acts as allosteric activator ；
ATP, acetyl-CoA, long chain fatty acids
and Ala in liver act as allosteric
inhibitors;

33. • Covalent modification:
phosphorylated by Glucagon
through cAMP and PKA and inhibited.
ATP ADP
PKA
Glucagon
Pyruvate Kinase
(active)
Pyruvate Kinase- P
(inactive)
cAMP

34. SIGNIFICANCE OF GLYCOLYSIS
• Glycolysis, the major pathway for glucose
metabolism, occurs in the cytosol of all cells.
It is unique in that it can function either
aerobically or anaerobically.
• Glycolysis is both the principal route for
glucose metabolism and the main pathway
for the metabolism of fructose, galactose, and
other carbohydrates derived from the diet.

35. • The ability of glycolysis to provide ATP in
the absence of oxygen is especially
important because it allows skeletal muscle
to perform at very high levels when oxygen
supply is insufficient and because it allows
tissues to survive anoxic episodes. However,
heart muscle, which is adapted for aerobic
performance, has relatively low glycolytic
activity and poor survival under conditions
of ischemia.

36. • Diseases in which enzymes of glycolysis (eg,
pyruvate kinase) are deficient are mainly seen
as hemolytic anemias or, if the defect affects
skeletal muscle (eg,phosphofructokinase), as
fatigue.

37. • In fast-growing cancer cells, glycolysis
proceeds at a higher rate forming large
amounts of pyruvate, which is reduced to
lactate and exported. This produces a
relatively acidic local environment in the
tumor which may have implications for
cancer therapy.

38. • The lactate is used for gluconeogenesis in the
liver, an energy expensive process which is
responsible for much of the hypermetabolism
seen in cancer cachexia.
• Lactic acidosis results from several causes
including impaired activity of PDH.

39. 3. Significance of glycolysis
1) Glycolysis is the emergency energy-
yielding pathway.
2) Glycolysis is the main way to
produce ATP in some tissues, even
though the oxygen supply is
sufficient, such as red blood cells,
retina, testis, skin, medulla of kidney.
• In glycolysis, 1mol G produces 2mol
lactic acid and 2mol ATP.

40. In the erythrocytes of many mammals, the
reaction catalyzed by phosphoglycerate
kinase may be bypassed by a process that
effectively dissipates as heat the free energy
associated with the high-energy phosphate
of 1,3-bisphosphoglycerate.
Bisphosphoglycerate mutase catalyzes the
conversion of 1,3-bisphosphoglycerate to
2,3-bisphosphoglycerate, which is converted
to 3-phosphoglycerate by 2,3-
bisphosphoglycerate phosphatase

41. (and possibly also phosphoglycerate
mutase). This alternative pathway involves
no net yield of ATP from glycolysis.
However, it does serve to provide 2,3-
bisphosphoglycerate, which binds to
hemoglobin, decreasing its affinity for
oxygen and so making oxygen more readily
available to tissues

42. § 3 Aerobic Oxidation of
Glucose

43. • The process of complete
oxidation of glucose to CO2 and
water with liberation of energy as
the form of ATP is named aerobic
oxidation.
• The main pathway of G oxidation.

44. 1. Process of aerobic oxidation
G Pyr
cytosol Mitochodria
glycolytic
pathway
second
stage
third
stage
CO2 + H2O+ATPPyr CH3CO~SCoA
first
stage
TAC

45. 1) Oxidative decarboxylation of
Pyruvate to Acetyl CoA
• irreversible;
• in mitochodria.
COO-
C
CH3
NAD+
NADH + H +
O
pyruvate
CH3C
Pyruvate
dehydrogenase
complex
Acetyl CoA
O
~SCoA+ HSCoA + CO2

46. Pyruvate dehydrogenase complex:
E1 pyruvate dehydrogenase
Es E2 dihydrolipoyl transacetylase
E3 dihydrolipoyl dehydrogenase
thiamine pyrophosphate, TPP (VB1
)
HSCoA (pantothenic acid)
cofactors lipoic Acid
NAD+
(Vpp)
FAD (VB2
)

47. HSCoA
NAD+
Pyruvate dehydrogenase complex:

48. The structure of
pyruvate dehydrogenase complex

49. S S
CH
H2
C
H2C (CH2)4 COOH
SH SH
CH
H2
C
H2C (CH2)4 COOH
+2H
- 2H
lipoic acid dihydrolipoic acid
C
C
NH2
HC
N
C
H2
S
C
C
N
C
N
C
H
CH3
CH2CH2H3C O P O
O-
O
P
O
O-
O-
+
TPP

50. HSCoA
HS CH2 CH2 NH C CH2
O
CH2 NH C C
O
OH
H
C CH2
CH3
CH3
O P O
OH
O
P
OH
O
O
3'AMP
¦Â-alanine pantoic acid pyrophosphate
pantothenic acid
4'-phosphopantotheine
¦Â-mercapto-
ethylamine

51. CO2
CoASH
NAD+
NADH
+H+

52. Regulation of PDH:
Two regulatory enzymes (that are part of the
complex) activate & inactivate E1
1. The cAMP-independent PDH kinase
phosphorylates &, thereby, inhibits E1
ATP, acetyl CoA & NADH are allosteric
activators of PDH kinase their presence
turns off the PDH complex.
Pyruvate is the inhibitor of PDH kinase its
presence activates PDH complex

53. 2. PDH phosphatase activates E1 by
dephosphorylation
Ca2+
is a strong activator of phosphatase,
stimulating E1 activity
Deficiency of PDH is the most common
biochemical cause of congenital lactic acidosis

54. (1) Pyruvate dehydrogenase complex
Pyruvate dehydrogenase
(active form)
allosteric inhibitors:
ATP, acetyl CoA,
NADH, FA
allosteric activators:
AMP, CoA,
NAD+
,Ca2+
pyruvate dehydrogenase
(inactive form)
P
pyruvate dehydrogenase
kinase
pyruvate dehydrogenase
phosphatase
ATP
ADPH2O
Pi
Ca2+
,insulin acetyl CoA,
NADH
ADP,
NAD+

55. 2) Tricarboxylic acid cycle, TCAC
• The cycle comprises the combination of a
molecule of acetyl-CoA with oxaloacetate,
resulting in the formation of a six-carbon
tricarboxylic acid, citrate. There follows a
series of reactions in the course of which
two molecules of CO2 are released and
oxaloacetate is regenerated.
• Also called citrate cycle or Krebs cycle.

56. (1) Process of reactions

59. fumarase

60. Citrate cycle
CO
CH2
COO
COO
CH3CO~SCoA
C
CH2
COO
COO
CH2
HO
COO
C
CH
COO
COO
CH2 COO
CH
CH
COO
COO
CH2 COO
H2O
H2O
HO
CO2
CH2
CH2
COCOO
COOCH2
CH2
COO
CO~ SCoA CO2
NAD+NADH+H+
CH2
CH2
COO
COO
GDP+PiGTP
CH
CH2
COO
COO
OOC CH
C COOH
HO
NAD+
NADH+H+
FAD
FADH2
H2O
acetyl CoA
H2O
oxaloacetate
citrate
synthase
citrate
aconitase
cis-aconitate
aconitase
isocitrate
NAD+
NADH+H+
isocitrate dehydrogenase
¦Á-keto-
glutarate
¦Á-ketoglutarate
dehydrogenase
complex
succinyl-CoA
ADP ATP
CoASH
succinyl CoA
syntetase
succinate dehydrogenase
fumarate
succinate
fumarase
malate
malate dehydrogenase
HSCoA
HSCoA

61. Summary of
Krebs Cycle
①
Reducing
equivalents

62. Bio-significance of TCA
1.Acts as the final common pathway for the
oxidation of carbohydrates, lipids, and
proteins.
2.Serves as the crossroad for the
interconversion among carbohydrates,
lipids, and non-essential amino acids, and
as a source of biosynthetic intermediates.

63. 3. Takes part in gluconeogenesis
All the intermediates of TCA are potential
glucogenic
4. Amino acid synthesis
The cycle serves as a source of carbon
skeleton for the synthesis of non essential
amino acids by transamination reactions e.g.
Alanine from pyruvate, aspartate from
oxaloacetate & glutamate from α-ketoglutarate
5. Takes part in fatty acid synthesis
Acetyl CoA formed from pyruvate
dehydrogenase, is the major substrate for long
chain fatty acids synthesis

64. Krebs Cycle is at the
hinge of metabolism.

65. ATP produced in the aerobic
oxidation of glucose
• 1 G → 2 pyruvate : 2 (NADH+H+
) → 6 or 8
ATP
• pyruvate →acetyl CoA: NADH+H+
→3 ATP
• acetyl CoA → TCAC : 3 (NADH+H+
) +
FADH2 + 1GTP → 12 ATP
• 1mol G ： 36 or 38mol ATP
（ 12 ＋ 3 ） ×2 ＋ 6 （ 8 ）＝
36 （ 38 ）

66. 3. The regulation of aerobic
oxidation
• The Key Enzymes of aerobic oxidation
The Key Enzymes of glycolysis
Pyruvate Dehydrogenase Complex
Citrate synthase
Isocitrate dehydrogenase (rate-limiting )
α-Ketoglutarate dehydrogenase

67. (2) Citrate synthase
• Allosteric activator: ADP
• Allosteric inhibitor: NADH, succinyl CoA,
citrate, ATP
(3) Isocitrate dehydrogenase
• Allosteric activator: ADP, Ca2+
• Allosteric inhibitor: ATP
(4) α-Ketoglutarate dehydrogenase
• Similar with Pyruvate dehydrogenase complex

69. Pentose Phosphate
Pathway

70. 1. The procedure of pentose
phosphate pathway/shunt
 In cytosol
Two phases
 Irreversible oxidative phase
 Reversible non oxidative phase

71. 1) Oxidative Phase
NADP+
NADPH+H+
H2O
CO2
G-6-P
Xylulose 5-P
Ribulose 5-P
Ribose 5-P
G-6-P
dehydrogenase
6-Phosphogluconate
6-phosphogluconate
dehydrogenase
6-Phospho
gluconolactonase
6-phosphogluco-
nolactone
Epimerase
Isomerase
NADP+
NADPH+H+

72. 2) Non-Oxidative Phase
Ribose 5-p
Xylulose 5-p
Xylulose 5-p
Fructose 6-p
Glyceraldehyde 3-p
Fructose 6-p
• Transketolase: requires TPP
• Transaldolase
Glycolysis

73. The net reation:
3G-6-P + 6NADP+
→
2F-6-P + GAP + 6NADPH + H+
+ 3CO2
2. Regulation of pentose phosphate
pathway
 Glucose-6-phosphate Dehydrogenase is the
rate-limiting enzyme.
NADPH/NADP+
↑, inhibit;
NADPH/NADP+
↓, activate.

74. 3. Significance of pentose
Phosphate pathway
1) To supply ribose 5-phosphate for bio-
synthesis of nucleic acid;
2) To supply NADPH as H-donor in
metabolism;
 NADPH is very important “reducing
power” for the synthesis of fatty acids
and cholesterol, and amino acids, etc.

75.  NADPH is the coenzyme of glutathione
reductase to keep the normal level of
reduced glutathione;
So, NADPH, glutathione and glutathione
reductase together will preserve the integrity of
RBC membrane.
2GSH
G-S-S-G NADPH + H+
glutathione reductase
NADP+H2O2
2H2O

76. Deficiency of glucose 6-phosphate
dehydrogenase results in hemolytic
anemia.
favism
 NADPH serves as the coenzyme of
mixed function oxidases (mono-
oxygenases). In liver this enzyme
participates in biotransformation.

77. Glycogen synthesis and
catabolism

78. Glycogen is a polymer of glucose
residues linked by
 α (1→4) glycosidic bonds, mainly
 α (1→6) glycosidic bonds, at
branch points

80. The process of glycogenesis
occurs in cytosol of liver and
skeletal muscle mainly
1. Glycogen synthesis (Glycogenesis)

81. Glycogen Synthesis

82. Glycogen Synthesis
• Glycogen is the major storage of glucose in animals and
many microorganisms (plants use starch)
• Glycogen synthesis can take place in all tissues, but is
especially predominant in
liver (100 gm make up10% w, <24 hr) and
muscle tissue (400 gm make up 1~2% w, exhausted
after <1hr vig activity)
•Fats cannot be converted to glucose in mammals, cannot be
catabolized anaerobically.
• Once stored in cytosolic granules, glycogen can be:
1. Broken down for distribution to other tissues (liver)
2. Broken down for glycolytic fuel to produce ATP
(muscle)

83. 1. First glucose is primed by
a) glucokinase (hexokinase IV in liver) or
b) hexokinase (hexokinase I or II in muscle)
D-Glucose + ATP  D-Glucose-6-phosphate + ADP
2. Next D-Glucose-6-phosphate is isomerized by
phosphoglucomutase
glucose-6-phosphate ↔ glucose-1-phosphate
Glycogen Synthesis

84. 3. Glucose is
charged with
UDP by
UDP-glucose
Pyro-
phosphorylase:
Note: it is
named for the
reverse
reactionFigure 15-7
glucose-1-P + UTP → UDP-glucose + 2Pi
Helps drive the reaction

85. 4. Glucose is transferred to the non-reducing end of
branched glycogen by glycogen synthase:
α14
linkage
•The free energy
change from
glucose-1-P to the
glycogen polymer
is highly favorable

87. 5. A block of residues is transferred to make a α1  6 linkage
from the growing α1  4 chain by the
glycogen branching enzyme:
Once 11 residues are built up, 6-7 are transferred to a branch.
Branching: solubility ↑, # of nonreducing ends ↑

88. Glycogenin catalyzes two
distinct reactions. Initial
attack by the hydroxyl group
of Tyr194
on C-1 of the
glucosyl moiety of UDP-
glucose results in a
glucosylated Tyr residue.
The C-1 of another UDP-
glucose molecule is now
attacked by the C-4 hydroxyl
group of the terminal
glucose, and this sequence
repeats to form a nascent
glycogen molecule of eight
glucose residues attached
by (α1→4) glycosidic
linkages.

89. Branching enzyme

90. Branching enzyme
• Amylo-α (1-4) α(1-6)-transglucosidase
transfers a chain of 6-8 glycosyl residues
from the non-reducing end of the glycogen
chain, and attaches it by an α(1-6) linkage,
thus functioning as 4:6 transferase.

91. Phosphorylase: key E;
The end products: 85% of G-1-P and 15%
of free G;
There is no activity of glucose 6-
phosphatase (G-6-Pase) in skeletal
muscle.
Gn
Pi Gn-1
G-1-P G-6-P
G-6-Pase
H2O Pi
G
Phosphorylase
2. Glycogen catabolism (glycogenolysis)

92. Glycogen Breakdown by phosphorolysis
• Glycogen is broken down by glycogen phosphorylase using Pi
to form glucose-1-phosphate (↔ glucose-6-P)

93. • A debranching enzyme
(oligo (α1→4) to (α1→6)
glucantransferase) catalyzes two
other reactions to transfer the
branches (left)
• Finally, phophoglucomutase
converts glucose-1-phosphate to
glucose-6-phosphate that can
then enter glycolysis (muscle).
• In liver, the glucose-6-phosphate
is converted to glucose by
glucose-6-phosphatase for
release to the blood

94. Debranching enzyme:
glucan transferase
α-1,6-glucosidase

95. Nonreducing ends
(α1→6) linkage
Glycogen
phosphorylase
(α1→6) glucosidase activity of
debranching enzyme Glucose
Transferase activity of
debranching enzyme

96. 3. Regulation of glycogenesis and
glycogenolysis
1) Allosteric regulation
In liver:
G phosphorylase
glycogenolysis
In muscle:AMP phosphorylase-b
ATP
G-6-P
phosphorylase-a
glycogenolysis
Ca2+

97. 2) Covalent modification
Glucagon
epinephrine
Adenylyl
cyclase
cAMP
G proteinreceptor
PKA
glycogenolysis
Phosphorylase
Glycogen synthase
glycogenesis
Blood sugar

98. glucagon, epinephrine
inactive
adenylate cyclase
active
adenylate cyclase
ATP cAMP
inactive
PKA
active
PKA
phosphorylase b
kinase
phosphorylase b
kinase
P
ATP
ADP
H2O
Pi
phosphorylase b
P
P
ATP ADP
Pi
H2O
ATP ADP
glycogen
synthase
glycogen
synthase
P
H2OPi
protein
phosphatase-1
(active) (inactive)
inhibitor-1
(active)
inhibitor-1
(inactive)
phosphorylase a
ATP

99. §6 Gluconeogenesis

100. • Concept:
The process of transformation of non-
carbohydrates to glucose or glycogen
is termed as gluconeogenesis.
• Substrates: lactate, glycerol, pyruvate
and glucogenic amino acid.
• Site: mainly liver
kidney

102. ⑤ Anaplerotic reaction of oxaloacetate
pyruvate carboxylase
Biotin
ATP ADP + Pi
+ CO2C
CH3
COOH
O
C
C
COOH
COOH
O
H2
NAD+
NADH+H+
malic acid DH
+ CO2
malic enzyme
C
CH3
COOH
O
NADPH+H+
NADP+
CHOH
C
COOH
COOH
C
C
COOH
COOH
O
H2H2

103. 1. Gluconeogenic pathway
• The main pathway for gluconeogenesis
is essentially a reversal of glycolysis,
but there are three energy barriers
obstructing a simple reversal of
glycolysis.

104. 1) The shunt of carboxylation of
Pyruvate
PEP
ADP
ATP
oxaloacetic acid
Pyr carboxylase
ADP+Pi ATP CO2
Biotin
GTP
GDP
CO2
PEP carboxykinase
Pyr kinase
COO
-
C
CH3
COO
-
CH
CH2
O~ P
O
pyruvate
COO
-
C
CH2
O
COOH £¨ Mt.£©
£¨ 1/3Mt. 2/3cytosal£©.

105. 2) F-1, 6-BP →F-6-P
F-6-P F-1,6-BP
ATP ADP
Pi H2O
PFK-1
Fructose-
bisphosphatase

106. 3) G-6-P →G
G G-6-P
ATP ADP
Pi H2O
Glucose-6-
phosphatase
HK

107. gluconeogenesis
glucose
G-6-P
glycogen
F-1,6BP
glyceral-
dehyde 3-P
glycerol
1.3-bisphospho-
glycerate
glycerate 3-P
glycerate 2-P
lactate
G-1-P
malic acid
phosphoenol
pyruvate
pyruvate
GTP
GDP
CO2
2/3
malic acid
pyruvate
phosphoenol
pyruvate
GTP
GDP
CO2
1/3
CO2
CYTOSOL MITOCHONDRIA
NAD+
NADH+H+
NAD+
NADH+H+
NAD+
NADH+H+
glutamate
¦Á-ketoglutarate ¦Á-ketoglutarate
glutamate
OAAAspAspOAADHAP
ATP
ADP
ATP
ADP
PK
ADP
ATP
F-6-P
Biotin

108. Key enzymes of gluconeogenesis
Pyr carboxylase
PEP carboxykinase
Fructose-bisphosphatase
Glucose-6-phosphatase

109. F-1,6-BP
ATP
ADP
Pi
H2O
PFK-1FBPase-1
F-6-P
F-2,6-BP
AMP
glycolysis
gluconeogenesis:

110. F-1,6-BP
ATP
ADP
F-2,6-BP
PEP
Pyr
acetyl CoA
glucagon
insulin
glucagon
Ala in liver
OAA

111. 3. Significance of gluconeogenesis
(1) Replenishment of Glucose by
Gluconeogenesis and Maintaining
Normal Blood Sugar Level.
(2) Replenishment of Liver Glycogen.
(3) Regulation of Acid-base Balance.

112. Lactic acid (Cori) cycle
• Lactate, formed by the oxidation of
glucose in skeletal muscle and by
blood, is transported to the liver where
it re-forms glucose, which again
becomes available via the circulation
for oxidation in the tissues. This
process is known as the lactic acid
cycle or Cori cycle.
• prevent acidosis ； reused lactate

113. muscle
glucose
pyruvate
lactate
glucose
blood
pyruvate
lactate
glycolytic
pathway
glucose
liver
lactate
NAD+
NADH+H+
NADH+H+
NAD+
gluconeo-
genesis
Lactic acid cycle

114. §6 Blood Sugar and Its
Regulation

115. 1. The source and fate of blood sugar
blood sugar
3.89¡« 6.11mmol/L
dietary supply
liver glycogen
(gluconeogenesis)
other saccharides
CO2 + H2O + energy
glycogen
other saccharides
non-carbohydrates
>8.89¡«10.00mmol/L
(threshold of kidney)
non-carbohydrate
(lipids and some
amino acids)
urine glucose
origin (income) fate (outcome)

116. Blood sugar level must be maintained
within a limited range to ensure the
supply of glucose to brain.
The blood glucose concentration is 3.89
～ 6.11mmol/L normally.

117. 2. Regulation of blood sugar level
1 ） insulin ： for decreasing blood sugar
levels.
2 ） glucagon ： for increasing blood sugar
levels.
3 ） glucocorticoid: for increasing blood
sugar levels.
4 ） adrenaline ： for increasing blood
sugar levels.

118. 3. Abnormal Blood Sugar Level
• Hyperglycemia: > 7.22 ～ 7.78 mmol/L
• The renal threshold for glucose: 8.89
～ 10.00mmol/L
• Hypoglycemia: < 3.33 ～ 3.89mmol/L

119. Stage 1 – postparandial
All tissues utilize glucose
Stage 2 – postabsorptive
KEY – Maintain blood glucose
Glycogenolysis
Glucogneogenesis
Lactate
Pyruvate
Glycerol
AA
Propionate
Spare glucose by metabolizing fat
Stage 3- Early starvation
Gluconeogenesis
Stave 4 – Intermediate starvation
gluconeogenesis
Ketone bodies
Stage 5 – Starvation

120. Pyruvate as a junction point