2/16/2014 1 Chapter 8 • regulation of metabolic pathways • regulation of glycolysis and gluconeogenesis • regulation of glycogen synthesis & breakdown Lecture 15: Regulation of Carbohydrate Metabolism Practice Questions See blackboard Regulation of metabolic pathways • living cells maintain a dynamic steady state – homeostasis • Regulatory Strategies 1) Enzymes responds to changes in metabolite concentration – Allosteric modulation 2) Covalent modification of enzymes: Hormone regulation protein phosphorylation - enzyme activity regulation
Transcript
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Chapter 8
• regulation of metabolic pathways
• regulation of glycolysis and gluconeogenesis
• regulation of glycogen synthesis & breakdown
Lecture 15: Regulation of Carbohydrate Metabolism
Practice Questions
See blackboard
Regulation of metabolic pathways
• living cells maintain a dynamic steady state – homeostasis
• Regulatory Strategies
1) Enzymes responds to changes in metabolite concentration –
Allosteric modulation
2) Covalent modification of enzymes: Hormone regulation
protein phosphorylation -
enzyme activity regulation
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How are these opposing pathways regulated?
Allosteric regulation!
PFK-1 FBPase-1
1
2
3
4
Reciprocal Regulation
Glycolysis and
gluconeogenesis do not
function at the same
time.
Both pathways are
exergonic, so there is no
energy barrier.
Pathways are regulated
by concentrations of
precursors (substrates),
intermediates, and
products.
PFK
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Regulation of PFK-1
(phosphofructokinase-1)
allosteric inhibition by ATP and citrate
allosteric activation by fructose 2,6-bisphosphate
Km altered by [ATP]
substrate – yellow and blue; inhibitor - blue
Regulation of pyruvate kinase
allosteric inhibition by ATP
glucagon leads to
reduced glycolysis
– how?
3
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Reciprocal Regulation
Glycolysis and
gluconeogenesis do not
function at the same
time.
Both pathways are
exergonic, so there is no
energy barrier.
Pathways are regulated
by concentrations of
precursors (substrates),
intermediates, and
products.
PFK
Regulation of Gluconeogenesis:
Pyruvate Carboxylase
gluconeogenesis is
regulated at the level of
pyruvate carboxylase
(activated by acetyl-CoA)
and FBPase-1 (which is
inhibited by fructose 2,6-
bisphosphate and AMP)
acetyl-Co-A turns off its own
production (slows down
glycolysis and enhances synthesis
of more glucose)
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Regulation of fructose 1,6-bisphosphatase-1
(FBPase-1) and phosphofructokinase-1 (PFK-1)
reciprocal allosteric regulation - opposite effects of fructose 6-
phosphate on PFK-1 and FBPase-1
F-2,6-BP
Regulation of Glycolysis in the Liver
F-6-P F-1,6 BP
F-2,6 BP
PFK2 FBPase2
PFK1
FBPase1
Glucose
Activator of PFK1
glycolysis
gluconeogensis
• The liver helps maintain blood-
glucose levels - stores glucose as
glycogen and releases glucose from
glycogen.
• In the liver PFK is inhibited by
citrate, a product of the citric acid cycle
(a pathway following glycolysis).
Citrate acts by enhancing the inhibitory
effects of ATP.
Feedforward stimulation
FBP: fructose
bisphosphatase
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Domain structure of bifunctional enzyme, phosphofructokinase 2
Recall F-6P -> F-2,6-BP
catalyzed by PFK-2
F-2,6-BP stimulates PFK
F-2,6-BP inhibits fructose-
1,6-bisphosphatase
(FBPase 2) in
gluconeogenesis
PFK-2 FBPase 2
Bifunctional
enzyme
This enzyme is regulated by
phosphorylation of a serine residue.
Control of the Synthesis and Degradation of F-2,6-BP
PKA
Glucagon is a hormone
that signals for
gluconeogenesis to occur.
Insulin is a hormone that
signals for glycolysis to
occur.
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Figure 8.21 Major Factors Affecting Glycogen Metabolism
increased glycogenolysis
increases [glucose] insulin leads to
decreased [glucose]
Glycogen Metabolism During Exercise or Fasting
Red: inactive
Blue: active
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Low Glucose in Blood! Epinephrine and Glucagon
The path of insulin to glycogen synthase
insulin turns on
glycogenesis,
reduces [glucose]
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Overview
Overview
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Low Glucose in Blood! Epinephrine and Glucagon
Liver hydrolyze glycogen to provide glucose in blood. Muscle
