Download Gluconeogenesis

Gluconeogenesis
Glycolysis (aerobic)
Glucose + 2 ADP + 2 phosphate + 2 NAD → 2 Pyruvate + 2 ATP + 2 NADH + 2 H2O
Gluconeogenesis
2 Pyruvate + 2 NADH + 4 ATP + 2 GTP → glucose + 2 NAD + 4 ADP + 2 GDP + 6 Pi
Substrates
NAD
O
NADH
O
Triacylglycerol
C O
C O
HO C H
C O
Lactate
dehydrogenase
CH3
L-Lactate
C O
Glycerol
O
C O
H3N CH
C O
Alanine
aminotransferase
CH3
Alanine
CH3
Pyruvate
O
CH2 C O
CH2
C O
O
O
NH4
NAD
NADH
H3N CH
Glutamate
Free fatty acids
Pyruvate
!-ketoglutarate Glutamate
O
CH3
CH2 C O
CH2
C O
Glutamate
dehydrogenase
C O !-ketoglutarate
O
Glucose
Glucose Metabolism
ATP
Pi
(Glycolysis, Gluconeogenesis, & Glycogen Synthesis)
Hexokinase
Glucokinase
Glucose-6phosphatase
ADP
Phosphoglucomutase
Glucose
Glucose-6-phosphate
1-phosphate
Phosphoglucoisomerase
UDP-glucose
pyrophosphorylase
Fructose-6-phosphate
PPi
UDP-Glucose
Phosphofructokinase
Fructose
bisphosphatase
Pi
Glycogen
UTP
ATP
Pi
Glycogen
Phosphorylase
Glycogen
synthase
Pi
ADP
Fructose-1,6-bisphosphate
Triose phosphate
isomerase
Aldolase
Dihydroxyacetone
Glyceraldehyde
+
phosphate
3-phosphate
NAD + Pi
NADH
Glyceraldehyde-3-phosphate
Glycerol-3-phosphate
dehydrogenase
dehydrogenase
NADH
NAD
Glycerol
1,3-Bisphosphoglycerate
Glycerol
kinase
Glycerol
ADP
3-phosphate
Phosphoglycerate
kinase
ADP
ATP
ATP
3-Phosphoglycerate
Phosphoglycerate
mutase
2-Phosphoglycerate
Enolase
Phosphoenolpyruvate
carboxykinase
Oxaloacetate
Phosphoenolpyruvate
ADP
GDP
+ CO2
Pyruvate
kinase
NAD
Lactate
Malate
dehydrogenase
NAD
ATP
NADH
Malate
Pyruvate
Lactate
dehydrogenase
Pyruvate
carboxylase
Alanine
NADH
GTP
Pyruvate
Aminotransferase
CoA-SH + NAD
Pyruvate
dehydrogenase
ATP
+ CO2
CO2 + NADH
Acetyl-CoA
Malate
NAD
Malate
dehydrogenase
NADH
Oxaloacetate
ADP
+ Pi
Citrate
Citrate
synthase
TCA Cycle
Citrate
Pyruvate
Liver
Glucose
Glucose
Muscle
Cori cycle
Lactate
Alanine
NH4
Protein
Pyruvate
Lactate
Alanine
Alanine cycle
Amino acids
!-ketoacids
Urea
NH4
Urea
Excretion
Products
Branched-chain
amino acids
Glutamine
Kidney
Brain
Synthesis of phosphoenolpyruvate from pyruvate
NH2
ATP
O
HO
C
O
O
O
O P O P O P O CH2
O
O
O
O
Carboxyphosphate
N
N
ADP
N
O P O
O
HO
Pi
N
O
HO C C CH2
O
O
NH
C N
NH
Carboxybiotinyl
enzyme
O
C
O
OH
OH
O
O C C CH2 H
O O
C
O
Pyruvate
O O
Enolpyruvate
O
O
N
H
N
S
Biotin
Lys-Enzyme
H
N
S
O
O
Lys-Enzyme
O
O O C O
O C C CH2
Oxaloacetate
O
O
GTP
CO2 + GDP
O O C O
O O
O C C CH2
O C C CH2
Oxaloacetate
O P O
Phosphoenolpyruvate
carboxykinase
Phosphoenolpyruvate
Glycogen
Glycogen
O
OH
Glycogen
CH2
OH
O
HO
OH
O
CH2
OH
HO
O
O
OH
OH
CH2
O
HO
4
!-1,4-Glucoside
bond
3
OH
2
HO
5
O
CH2 O
6
!-1,6-Glucoside
bond
O
1
O
Glycogen
Glucose phosphate interconversion
O
O P O
O
CH2
H
H
OH
HO CH2
O
H
OH
H
OH
H
H
H
OH
OH
H
O
H
OH
Phosphoglucomutase
O P O
H
Glucose-6-phosphate
O
OH
Glucose-1-phosphate
O
O P O
O CH2
H
O
H
OH
H
H
OH
OH
H
O
O P O
O
Glucose-1,6-bis-phosphate
O
Glycogen Synthesis
O
Uridine Triphosphate
(UTP)
O
O
O P O
P
O
O
HN
P
O
CH2 O
O
+
H
H
OH
H
OH
H
HO CH2
N
O
O
O
UDP-Glucose
Pyrophosphorylase
H
H
OH
O
H
H
OH
H
O
O
O
O P O
P
O
O
H
OH
O P O
HN
H
O
H
OH
O
H
OH
HO CH2
H
O
UDP-Glucose
OH
O
O
Glucose-1-phosphate
O
H
H
OH
H
OH
H
+
Pyrophosphate
N
CH2 O
O
O P O P OH
O
O
Pyrophosphatase
O
+
O P OH
O
O P OH
O
O
ADP-Glucose
Pyrophosphorylase
ADP-Glucose + Pyrophosphate
ATP + Glucose-1-Phosphate
OH
HO
HO
O
UDP-Glucose
HN
O
HO
O
O
O P O
P
O
O
CH2 O
O
H
H
OH
H
OH
H
Glycogen
synthase
HO CH2
OH
UDP
N
O
O+
HO
HO
H
+
H
OH
HO CH2
O
H
H
O
H
OH
H
H
OH
H
O
OH
OH
H
H
OH
n
Glycogen
Glycogen
synthase
HO CH2
HO CH2
H
H
OH
O
H
H
H
H
OH
HO CH2
O
H
OH
H
H
O
H
OH
H
H
OH
H
O
O
OH
H
H
OH
Glycogen
n
Branching
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Glycogen Breakdown
HO CH2
H
H
OH
P
Glycogen
Phosphorylase
HO CH2
O
H
H
H
H
OH
H
O
HO CH2
H
H
H
OH
H
H
H
OH
OH
n
Glycogen
H
O P OH
H
O
H
OH
O
OH
H
H
OH
Glycogen
H
O
H
HO
O P O
H
OH
O
Glucose-1-phosphate
!
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O
H
OH
H
O
HO CH2
O
H
H
HO
O
HO
HO CH2
O
!
!
!
n–1
Thermodynamic Considerations
Reaction
∆G´° (kJ/mol)
∆G (kJ/mol)
G-1-P + glycogenn  glycogenn+1 + Pi
–3.1
+5 to +8 because
[Pi] >> [G1P]
UDP-Glucose pyrophosphorylase
G-1-P + UTP  UDPG + PPi
0
Pyrophosphatase
PPi  2 Pi
–33.5
Glycogen synthase
UDP + glycogenn  glycogenn+1 + Pi
–13.4
Glycogen phosphorylase
glycogenn + Pi  G-1-P + glycogenn–1
+3.1
Hydrolysis of α(14)
–15.5
Hydrolysis of α(16)
–7.1
H
H
OH
O
H
OH
H
O
UDP-Glucose
HO CH2
OH
O
HN
H
O
O
O P O
P
O
O
N
O
O
–5 to –8 because
[Pi] >> [G1P]
2 NADH
2 NAD
+
H2O
H
OH
O
H
OH
CH2 O
H
H
OH
H
OH
H
O C
H
UDP-Glucose
dehydrogenase
H
O
UDP-Glucuronic acid
OH
HN
H
O
O
O P O
P
O
O
N
O
O
CH2 O
H
H
OH
H
OH
H