ANABOLISM
Gluconeogenesis
and glycogen
Case of animal cells
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ANABOLISM
(INTRODUCTION)
 Anabolism is defined as the metabolism used to
synthesize molecules that the body needs.
 As opposite to the catabolism, anabolism of aerobic systems
proceeds in general by reduction reactions. The involved
dehydrogenases very often use NADPH.
INTRODUCTION ANABOLISM
The comparison of the catabolic and anabolic pathways
highlights three different cases:
 The anabolic and catabolic pathways are totally
different.
 Both use the same enzymes for all reversible
reactions. Only the irreversible steps are different:
Example glycolysis, gluconeogenesis
The metabolic steps are nearby, but many enzymes
differ; In addition, the two metabolisms are located
generally in different compartments.
Examples: anabolic and catabolic Lynen spirals
example
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Gluconeogenesis
Balance - localisation
 The main source of substrate is pyruvate/lactate or
 Gluconeogenesis is localized in the cytosol
 This anabolism is very close to Glycolysis
 Only irreversible steps are replaced by other reactions (or
system of reaction) resulting from the point of view of the
substrate to the inverse transformation (1).
Coment
•
(1) it is obvious that the balance reaction is different.
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Remeber
glycolysis
(Irreversible steps in red)
CHO Glucose
(4)
Aldolase
OH
Glycéraldéhyde-3P
H
CH2OP
CHO
OH
DHP
O
H
OH
OH
(5)
CH2OH
CH2OP
CH2OH
Isomérase
NAD+
ATP Gluckonase
(6)
(1)
ou Hexokinase
G3PDH
NADH
ADP
COOP
CHO
H
OH Glycérate1-3P
H
OH
CH2OP
HO
H
ADP
H
OH G6P
Glyc.-3P kinase (7)
ATP
H
OH
COOCH2OP
H
OH Glycérate-3P
G6P isomérase
CH2OP
(2)
H
HO
H
H
CH2OH
O
HO
H
Isomérase(8)
COOFructose-6P (F6P)
H
OP Glycérate-2P
OH
CH2OH
OH
Enolase (9)
CH2OP
H2O
ATP
COO(3)
Phosphofructokinase
Phosphoénolpyruvate
(PEP)
ADP
OP
CH2OP
CH2
O
ADP
Pyruvate kinase (10)
HO
H
ATP
F1-6P
H
OH
COOCOO(11)
H
OH
Pyruvate
H
OH Lactate
O
CH2OP
CH3
CH3
NADH NAD+
H
H
Lactate DH
Irréversible reactions in glycolysis
•
–
Glucokinase (or hexokinase) : Glucose + ATP  G6P + ADP (DG’°= -15 kJ)
–
Phosphofructokinase : F6P + ATP  F1-6P + ADP (DG’°= -15 kJ)
–
Pyruvate kinase : PEP + ADP  Pyruvate + ATP (DG’°= -30 kJ)
Coments
 DG’° values are approximative by simplification. The values are respectively17, -14, -31 kJ.
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Corresponding reactions on gluconeogenesis
Glucose-6P  Glucose : G6P phosphatase (G6Pase) G6P  Glucose + P (DG’°= -15 kJ) (2)
Fructose1-6P  F6P : F1-6P phosphatase (F1-6Pase) F1-6P  F6P + P
(DG’°= -15 kJ)
ADP ATP
Cytosol
Cytosol
Mitochondrie
ATP ADP + P
NADH NAD+
COOCOOCHOH
Pyruvate
C O
CH2
CH2
CO2
COOCOO
COOC O
CH3
Pyruvate
GTP GDP
COOOAA
C OP
CH2
CO2
NAD+ NADH
Malate
Malate
OAA
Pyruvate carboxylase
MDH
MDH
PEP carboxykinase
 Only malate and pyruvate are able to be transported, which explains
the intervention of MDH in two compartments.
H
HO
H
H
P
G 6Pa se
H
HO
H
H
CHO
G lu cose
OH
H
OH
DHP
OH
C H 2O H
A TP G luc konase
ADP
Aldolase
G lyc érald é hyd e -3P
C H 2O P
O
C H 2O H
o u Hex okinase
H
Isom érase
P
F16P ase
HO
H
H
C y tosol
Comparaison
Glycolyse-Gluconeogenesis
NADH
H
H
O H G 6P
OH
C H 2O P
COOP
O H G lycéra te1 -3P
C H 2O P
A DP
G lyc.-3P kin ase
A TP
COO
O H G lycéra te-3P
C H 2O P
-
H
C H 2O H
O
H
Fru ctose-6 P (F6P )
OH
OH
C H 2O P
A TP
ADP
C H 2O P
O
C H 2O P
NAD+
G 3P D H
CHO
OH
G 6 P iso m érase
HO
H
H
CHO
OH
Iso m érase
H
COO O P G lycéra te-2P
C H 2O H
M ito cho nd rie
H2O
En ola se
G D P G TP N A D H N A D +
COO CO O H
OH
OAA
M a la te
OP
CH2
C H 2 PEP carboxyk inase M DH
M a la te
COOADP
P yru vate k in ase
(1 0)
N A D+
MDH
ATP
COO NADH
COOPyruvate
O
Pyruvate
O
CH3
ATP ADP CH2
CO
ONADH
OAA
L actate DH
Pyru vate carbo xylase
NAD+
COO-
P hosp ho fructokinase
H
O H F1-6P
OH
C H 2O P
PEP
Lac tate H
OH
CH3
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Regulation
•The activity of the enzymes controlling the irreversible steps (key enzymes)
(GK, KFC, Pyruvate K) in glycolysis and gluconeogenesis (F1-6Pase, G6Pase)
depends on the concentration of intracellular or extracellular substrates
(hormones)
•This allows, according to the physiological state, to activate either Glycolysis
or gluconeogenesis.
Example
A high concentration of ATP intracellular (ex: liver cell at rest) causes the
activation of the G6Pase and F1-6Pase and inhibition of the GK, the KFC and
the PK.
Inversely, a high concentration of ADP and AMP intracellular (liver cell late
anabolic activity) causes inhibition of the G6Pase and F1-6Pase and the
activation of the GK, the KFC, and the PK.
It results that:
– When the cell is in deficit of ATP (thus energy), glycolysis (and thus the
Krebs cycle) are activated. When the cell has a high concentration of ATP,
it triggers gluconeogenesis.
Other gluconeogenesis
Any substrate for the synthesis of malate can be used as a
source of gluconeogenesis.
This is the case of the Krebs cycle except the AcetylCoA intermediaries
since AcetylCoA enters the Krebs cycle only by reacting with OAA to
form citrate..

CH3COSCoA
OAA
Citrate
2 CO2
There is no synthesis of OAA or malate. So it may not be of gluconeogenesis.
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Synthesis of glycogen
 Structure
Synthesis of glycogen
 Importance
Glycogen
Glucose
Unlike glycogen, fatty acids
cannot be converted into
glucose.
Glycolysis
Pyruvate
Fatty acid
Acetyl-CoA
 Fatty acids provide energy
only in the presence of
oxygen, glycogen can provide
in the absence.
Krebs
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Synthesis of glycogen
 Formation of glucose-1P
Glucose-6P
Glucose-1P
Enzyme: Phosphoglucomutase
Synthesis of glycogen
 Formation of UDP-glucose
Glucose-1P + UTP
UDP-Glucose + PPi
Enzyme: UDP-glucose pyrophosphorylase
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Synthesis of glycogen
 Glycosylation of the elongating glycogen chain
UDP-Glucose-1P + n glc
UDP + (n+1) glc
Enzyme: Glycogen synthase
Synthesis of glycogen
 Ramification
• The branches are formed by transferring glucose through links 16 at the end of chain.
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Synthesis of glycogen
 Lengthening of the chain by 1-4 links
Note :
• The degradation of glycogen to the Glucose-1-P is irreversible. The synthesis
replaces this step by a sequence of reactions that are transforming the glucose-1P
in Glucose-UDP which serves as a source of glucose for glycogen. This allows the
reversal of the sequence.
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