BIOC 460 - DR. TISCHLER LECTURE 26

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BIOC 460 - DR. TISCHLER LECTURE 26
GLYCOLYSIS AND GLUCONEOGENESIS-2
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OBJECTIVES

• Gluconeogenesis Pathway
• Key liver gluconeogenic precursors 4 unique rxns
• relationship between nutritional status (i.e.,
  fed or starved) and the amount of
  phosphoenolpyruvate carboxykinase in liver cells
  as well as the significance of these responses .
• Significance of the glyceraldehyde-3-phosphate
  dehydrogenase and phosphoglycerate kinase
  reactions in gluconeogenesis

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Regulation of Glycolysis and Gluconeogenesis 1.
Kinetics and allosteric regulation of glucokinase
and hexokinase logic for differences between the
two kinases. 2. Regulation of PFK-1 and
F-1,6-BPase a) compare allosteric
regulation. b) regulation coordinates
glycolysis and gluconeogenesis c)
metabolism of F-2,6-BP role of bifunctional
protein d) insulin via F-2,6-BP
ensures during the fed state that liver
glycolysis is active and gluconeogenesis is
inactive 3. Regulation of pyruvate kinase via
allosteric control and by covalent modification
(phosphorylation/ dephosphorylation)
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G6Pase
unique
Glucose
Glucose 6-P
precursor
Fructose 6-P
glycolytic enzyme also
F1,6BPase
F-1,6-BP
G-3-P DHAP
NAD
Figure 1. Gluconeogenic pathway for lactate, ala,
asp, glycerol
G-3-P DH
NADH
ADP Pi
PGK
ATP
Pyruvate
CYTOPLASM
PEP
PC
PEPCK
Pyruvate
OAA
PEP
MITOCHONDRION
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Unique Reaction 1 Pyruvate carboxylase
catalyzes the reaction pyruvate ATP CO2 ?
oxaloacetate ADP Pi
CO2
CO2
CO2
CO2
CO2
OC-OH
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Unique Reaction 2 Phosphoenolpyruvate
carboxykinase (PEPCK) catalyzes the reaction
oxaloacetate GTP ? phosphoenolpyruvate GDP
CO2
PO3
CO2
PO3
CO2
PO3
CO2
PO3
PO3
CO2
CO2
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Unique Reaction 3 Fructose-1,6-bisphosphatase
catalyzes the reaction Fructose-1,6-bisphosphat
e ? Fructose-6-phosphate Pi
PO3
PO3
PO3
PO3
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Unique Reaction 4 Glucose-6-phosphatase
catalyzes the reaction Glucose-6-phosphate ?
Glucose Pi
PO3
PO3
PO3
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COMPARATIVE KINETICS OF HEXOKINASE AND
GLUCOKINASE

• Hexokinase
• has low Km (high affinity) for glucose
• ensures brain, red blood cells, etc can use
  
• glucose even when blood low in starvation
• Glucokinase
• has high Km (low affinity) for glucose
• ensures that liver or pancreas only uses
  glucose
• in response to high blood levels after a
  meal

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No allosteric control


Hexose-6-P (G6P most Tissues)
Glucose-6-P


Figure 2. Regulation of glucokinase and
hexokinase
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Fructose-6-phosphate
ATP
Pi

Citrate
fructose-2,6-bisP
PFK-1

H
F-1,6-BPase

(glycolysis)
(gluconeogenesis)
fructose-2,6-bisP


H2O
ADP
Fructose-1,6-bisphosphate
Figure 3 Reciprocal regulation of glycolysis
and gluconeogenesis at reactions catalyzed by
phosphofructokinase-1 and fructose-1,6-bisphospha
tase.
- allosteric inhibition allosteric
activation
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Figure 4. Reactions in the metabolism of
fructose-2,6-bisphosphate.
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Figure 5. Formation of F-2,6-bisP in the fed
state leads to activation of PFK-1 in glycolysis
and inactivation of gluconeogenesis.
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Figure 6. Regulation of liver pyruvate kinase.