Chapter 17 Storage Mechanisms

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Chapter 17 Storage Mechanisms Control of
Carbohydrate Metabolism
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Glycogen breakdown Glycogen synthesis Regulation
of glycogen metabolism Gluconeogenesis Pentose
phosphate pathway
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Part of a larger picture
Glycogen degradation
Glycogen synthesis
Glucose
Pentose-P
Glycolysis
Gluconeogenesis
Pyruvate
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1. Glycogen Breakdown
Glycogen is stored in the muscle liver.
Glucose can be released rapidly if energy is
needed Fight or flight mechanism
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(Glucose)n
Glycogen
Glycogen phosphorylase
(Glucose)n-1
O
Remainder of glycogen
Glucose-1-P
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-H -OH
H2O ?
Hydrolysis
P ?
-H
P
P phosphate
Phosphorolysis
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Glycogen
Glycogen(n-1)

Glycogen-1-P
Glucose P
Conversion to Glucose-6-P
Exported Regulates blood sugar
Glycolysis
Liver
Muscle
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Phosphoglucomutase
Glucose-1-P Glucose-6-P
Glycolysis
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Glycogen debranching enzyme
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Glycogen hydrolysis

• Glycogen phosphorylase
• Phosphoglucose mutase
• Glycogen debranching enzyme

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In muscle. Glycolysis is starte with glucose-6-P.
Only 1 ATP is need for activation. 4 ATPs are
produced. The net ATP production is 3.
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Part of a larger picture
Glycogen degradation
Glycogen synthesis
Glucose
Pentose-P
Glycolysis
Gluconeogenesis
Pyruvate
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2. Glycogen Synthesis

• Glucose-6-P ?? Glucose-1-P

2. Glucose-1-P UTP
Uridine triphophate
UDP-glucose PPi
UDP-glucose pyrophosphorylase
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Where do you get the UTP? 3. ATP UDP ?? ADP
UTP
UTP uracil-ribose-PPP
Split it here Attach uracil-ribose-P Activates
the glucose-phosphate
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4. PPi ? 2 Pi
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Energetics
Glucose-1-P UTP ? ? UDP-glucose PPi
DGo 0 kcal/mole
PPi ? 2 Pi
DGo -7.3 kcal/mol
Glucose-1-P UTP ? UDP-glucose 2Pi
DGo -7.3 kcal/mol
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Glycogen synthase
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Branching Enzyme
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Enzymes involved in glycogen synthesis

• UDP-glucose pyrophosphorylase
• Glycogen synthase
• Branching enzyme

Uses 1 high energy bond/ glucose
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Part of a larger picture
Glycogen degradation
Glycogen synthesis
Glucose
Pentose-P
Glycolysis
Gluconeogenesis
Pyruvate
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Glycogen synthesis and breakdown should not
occur at the same time. Why?
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Regulation of glycogen metabolism
How are enzymes regulated? 1. Allosteric
modifier binds to enzymes changes enzyme
shape alters activity milliseconds
2. Covalent modification of the enzyme
phosphorylation seconds to minutes
3. Control enzyme synthesis
4. Regulation by hormones
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Covalent modification
Glycogen phosphorylase
2ATP
- P
P-
-2 Pi
Glycogen phosphorylase b Active
form phosphorylated
Glycogen phophorylase a Inactive
form dephosphorylated
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Kinase phosphorylates a substrate
Gets energy from hydrolysis of ATP Phosphatase -
Removes a phosphate from a substrate.
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Glycogen synthetase
2ATP
- P
P-
-2 Pi
Glycogen synthase D Inactive form phosphorylated
Glycogen synthase I Active form dephosphorylated
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Effect on Activity
Phosphorylase Synthase


Phosphorylation Increases
Decreases
Dephosphorylation Decreases Increases
Epinepherine
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Allosteric Regulation glyogen phosphorylase
Liver phosphorylase b is turned off by
glucose.
Muscle phosphorylase a is turned off by ATP
and glucose 6-P. Energy supply high turned
on by AMP Energy supply low
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Part of a larger picture
Glycogen degradation
Glycogen synthesis
Glucose
Pentose-P
Glycolysis
Gluconeogenesis
Pyruvate
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3. Gluconeogenesis
What happens to the lactate formed in muscle
during strenuous exercise.
The lactate is transported to the liver where it
is converted to glucose by the process of
gluconeogenesis.
The glucose is then transported to the
muscle where it is converted to lactate ATP.
Cori cycle.
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Liver gluconeogenesis Requires 2 GTP 2ATP 2
Lactate?Glucose
Blood
Muscle - glycolysis Glucose?2 lactate
2ATP
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Gluconeogenesis formation of glucose from
pyruvate
III
II
3 irreversible reactions.
I
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1. Pyruvate to phosphoenol pyruvate
A. Pyruvate to oxaloacetate B. Oxaloacetate to
phosphoenol pyruvate
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A. Pyruvate ? Oxaloacetate


Pyruvate
ATP CO2 H2O ?? Oxaloacetate (4C)
ADP Pi 2H
(3C)
Pyruvate carboxylase
Biotin
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Carboxylase adds a carboxyl group to a
substrate requires biotin
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B. Oxaloacetate ? Phosphoenolpyruvate

Phosphoenolpyruvate CO2 GDP
Oxaloacetate
GTP ?
Phosphoenolpyruvate carboxy kinase
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Total reaction
Pyruvate ATP GTP
Phosphoenolpyruvate ADP GDP 2Pi
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Gluconeogenesis formation of glucose from
pyruvate
III
II
3 irreversible reactions.
I
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II
Fructose-1,6-bisphosphate H2O?
fructose-6-P Pi Fructose
1,6-bisphosphatase
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Gluconeogenesis formation of glucose from
pyruvate
III
II
3 irreversible reactions.
I
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III
Glucose-6-phosphate H2O ? Glucose Pi
Glucose-6-phosphatase
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Control of phosphofructokinase and
fructose-1,6-bisphophatase
Why does it need to be controlled?
Fructose-6-P ATP ? Fructose-1,6-bisP ADP
phosphofructokinase
Fructose-1,6-bisP H2O ? Fructose-6P P
fructose-1,6-bisphosphatase
ATP H2O ? ADP P
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F2,6P
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Glycolysis - phosphofructokinase
Inhibited by ATP
Stimulated by fructose-2,6P
Gluconeogenesis fructose-1,6-bisphosphatase
Inhibited by AMP, stimulated by ATP
Inhibited by fructose-2,6P
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The Cori Cycle There is no such thing as a free
lunch.
Glycolysis Glucose 2NAD 2P ?
2 Pyruvate 2NADH 2ATP H2O
Gluconeogenesis 2 Pyruvate 2NADH 4ATP 2GTP
6H2O ? Glucose 2NAD 2GDP
6P
G
Overall 2ATP 2GTP 4H2O ? 2ADP 2GDP 4P
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Part of a larger picture
Glycogen degradation
Glycogen synthesis
Glucose
Pentose-P
Glycolysis
Gluconeogenesis
Pyruvate
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5. The Pentose Phosphate Pathway
Start with glucose
Produces ribose and other pentoses NADPH
reduction in biosynthesis