Regulation of Gluconeogenesis

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Regulation of Gluconeogenesis
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FUTILE CYCLE
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FUTILE CYCLE !
Fructose-1,6-Bis P ADP
Fructose-6-P ATP
Fructose-6-P Pi
Fructose-1,6-bis P H2O
ADP Pi
Sum ATP H2O
RECIPROCAL REGULATION
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Function of Gluconeogenesis

• Provides glucose for export to other tissues when
  glycogen stores are depleted.
• Need to be activated when plasma glucose levels
  fall
• What signals changes in plasma glucose
  levelsHormones
• GNG need to be able to respond to changes in
  hormonal levels

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Reciprocal regulation of Gluconeogenesis and
glycolysis by hormones
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Role of F-2,6 Bis P in regulation of glycolysis
and gluconeogenesis
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• F 2,6-BP increases the apparent affinity
• of PFK for F-6-P

Fructose-2,6-Bis Phosphate Allosteric ACTIVATOR
of PFK-1
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• Fructose-2,6-Bis Phosphate
• Allosteric INHIBITOR of F 1,6-Bis Phosphatase

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Regulation of F-2,6-Bis P Levels
BIFUNCTIONAL ENZYME
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Regulation of enzyme activity

• Allosteric regulation
• Enzyme contains 2 different sites (Catalytic
  regulatory)
• Binding of regulator causes a confirmational
  change
• Either inhibition or activation
• NOTE The conformational change

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• Covalent modification
• A group is covalently introduced into the
  enzyme
• Most common Phosphate
• become esterified to amino acid side-chains
  that have alcohol groups (i.e. Ser, Thr, Tyr)

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Fully 2 of the genes in the human genome code
for protein kinases
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Conformational changes of enzymes

• Phosphorylation may activate one particular
  enzyme and inhibit another
• Many regulatory enzymes exist in two
  conformations
• Active enzyme Inactive enzyme
• Activation Push equilibrium to the left (More of
  the active enzyme, stabilize the active
  conformation)
• Inhibition Push equilibrium to the right (More
  of the inactive enzyme)

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cAMP- A second messenger
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