lecture 8 - glycogen metabolism
DESCRIPTION
Lecture 8 - Glycogen Metabolism. Chem 454: Regulatory Mechanisms in Biochemistry University of Wisconsin-Eau Claire. Introduction. Glycogen A storage form of glucose. Introduction. Glycogen is stored primarily in the liver and skeletal muscles. - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/1.jpg)
Chem 454: Regulatory Mechanisms in Biochemistry
University of Wisconsin-Eau Claire
Chem 454: Regulatory Mechanisms in Biochemistry
University of Wisconsin-Eau Claire
Lecture 8 - Glycogen MetabolismLecture 8 - Glycogen Metabolism
![Page 2: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/2.jpg)
22
GlycogenA storage form of glucose
GlycogenA storage form of glucose
IntroductionIntroduction
![Page 3: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/3.jpg)
33
Glycogen is stored primarily in the liver and skeletal muscles.
Liver - used for maintaining blood glucose levelsMuscles - used to meet energy needs of the muscles
Glycogen is stored primarily in the liver and skeletal muscles.
Liver - used for maintaining blood glucose levelsMuscles - used to meet energy needs of the muscles
IntroductionIntroduction
![Page 4: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/4.jpg)
44
Glycogen degradation occurs in three steps
Glycogen degradation occurs in three steps
IntroductionIntroduction
![Page 5: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/5.jpg)
55
Glycogen synthesis uses activated precursor UDP–glucose
Glycogen synthesis uses activated precursor UDP–glucose
IntroductionIntroduction
![Page 6: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/6.jpg)
66
Regulation of glycogen metabolism is complex.
Allosteric regulation to meet the needs of the cellHormonal regulation to meet the needs of the organsim
Regulation of glycogen metabolism is complex.
Allosteric regulation to meet the needs of the cellHormonal regulation to meet the needs of the organsim
IntroductionIntroduction
![Page 7: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/7.jpg)
77
Requires three enzymes and produces glucose 6–phosphate
Glycogen Phosphorylase
Debranching Enzyme
Phosphoglucomutase
In the liver, an additional enzyme produces free glucose
Glucose 6–phosphatase
Requires three enzymes and produces glucose 6–phosphate
Glycogen Phosphorylase
Debranching Enzyme
Phosphoglucomutase
In the liver, an additional enzyme produces free glucose
Glucose 6–phosphatase
1. Glycogen Breakdown1. Glycogen Breakdown
![Page 8: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/8.jpg)
88
Cleavage uses orthophosphate in phosphorolysis reactions
Cleavage uses orthophosphate in phosphorolysis reactions
1.1 Phosphorylase1.1 Phosphorylase
![Page 9: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/9.jpg)
99
Two enzymes activities are needed to deal with the α–1,6 branch points
Two enzymes activities are needed to deal with the α–1,6 branch points
1.2 Debranching Enzyme1.2 Debranching Enzyme
![Page 10: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/10.jpg)
1010
Mechanism is like that of phosphoglycerate mutase
Mechanism is like that of phosphoglycerate mutase
1.3 Phosphoglucomutase1.3 Phosphoglucomutase
![Page 11: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/11.jpg)
1111
Enzyme is found primarily in the liver and is used to release glucose into the bloodstream
Enzyme is found primarily in the liver and is used to release glucose into the bloodstream
1.4 Glucose 6-phosphatase1.4 Glucose 6-phosphatase
![Page 12: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/12.jpg)
1212
1.5 Mechanism for Phosphorolysis1.5 Mechanism for Phosphorolysis
![Page 13: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/13.jpg)
1313
1.5 Mechanism for Phosphorolysis1.5 Mechanism for Phosphorolysis
Pyridoxyl phosphate coenzyme
Pyridoxyl phosphate coenzyme
![Page 14: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/14.jpg)
1414
1.5 Mechanism for Phosphorolysis1.5 Mechanism for Phosphorolysis
![Page 15: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/15.jpg)
1515
Phosphorylase is regulated by several allosteric effectors that signal the energy state of the cell
It is also regulated by reversible phosphorylation in response to the hormones insulin, epinephrine, and glucagon
Phosphorylase is regulated by several allosteric effectors that signal the energy state of the cell
It is also regulated by reversible phosphorylation in response to the hormones insulin, epinephrine, and glucagon
2. Regulation of Phosphorylase2. Regulation of Phosphorylase
![Page 16: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/16.jpg)
1616
2.1 Muscle Phosphorylase2.1 Muscle Phosphorylase
![Page 17: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/17.jpg)
1717
2.1 Muscle Phosphorylase2.1 Muscle Phosphorylase
![Page 18: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/18.jpg)
1818
2.1 Muscle Phosphorylase2.1 Muscle Phosphorylase
![Page 19: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/19.jpg)
1919
2.2 Liver Phosphorylase2.2 Liver Phosphorylase
![Page 20: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/20.jpg)
2020
2.3 Phosphorylase Kinase2.3 Phosphorylase Kinase
![Page 21: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/21.jpg)
2121
Epinephrine and glucagon signal the need for glycogen breakdown
Epinephrine stimulates glycogen breakdown to a greater extent in the muscle than the liver.
Epinephrine and glucagon signal the need for glycogen breakdown
Epinephrine stimulates glycogen breakdown to a greater extent in the muscle than the liver.
3. Epinephrine and Glucagon3. Epinephrine and Glucagon
![Page 22: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/22.jpg)
2222
Epinephrine and glucagon signal the need for glycogen breakdown
Glucagon is a peptide hormone that is secreted by the α–cells of the pancreases when blood glucose levels are low
Epinephrine and glucagon signal the need for glycogen breakdown
Glucagon is a peptide hormone that is secreted by the α–cells of the pancreases when blood glucose levels are low
3. Epinephrine and Glucagon3. Epinephrine and Glucagon
![Page 23: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/23.jpg)
2323
Epinephrine binds to a 7TM receptorEpinephrine binds to a 7TM receptor
3.1 G-protein Signal Transduction3.1 G-protein Signal Transduction
![Page 24: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/24.jpg)
2424
Glucagon also binds to a 7TM receptorGlucagon also binds to a 7TM receptor
3.1 G-protein Signal Transduction3.1 G-protein Signal Transduction
![Page 25: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/25.jpg)
2525
In the liver, epinephrine also binds to α–adrenergic receptors, which activate the phosphoinositide signal transduction pathway
Release of inositol 1,4,5–trisphosphate by phospholipase C induces the release of Ca2+ from the ER.Binding of Ca2+ to calmodulin partially activates phosphorylase kinase
In the liver, epinephrine also binds to α–adrenergic receptors, which activate the phosphoinositide signal transduction pathway
Release of inositol 1,4,5–trisphosphate by phospholipase C induces the release of Ca2+ from the ER.Binding of Ca2+ to calmodulin partially activates phosphorylase kinase
3.1 α–Adrenergic Receptors in Liver3.1 α–Adrenergic Receptors in Liver
![Page 26: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/26.jpg)
2626
3.1 α–Adrenergic Receptors in Liver3.1 α–Adrenergic Receptors in Liver
![Page 27: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/27.jpg)
2727
3.2 Turning It Off3.2 Turning It Off
Glycogen breakdown can also be rapidly turned off.
GTPase activity of the G–proteins
cAMP phosphodiesterase
Protein kinase A also phophorylates the α–subunit of phosphorylase kinase. This makes it more susceptible to dephosphorylation (inactivation) by protein phosphatase 1 (PP1)
Glycogen breakdown can also be rapidly turned off.
GTPase activity of the G–proteins
cAMP phosphodiesterase
Protein kinase A also phophorylates the α–subunit of phosphorylase kinase. This makes it more susceptible to dephosphorylation (inactivation) by protein phosphatase 1 (PP1)
![Page 28: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/28.jpg)
2828
Different pathways are used for the synthesis and degradation.
Different pathways are used for the synthesis and degradation.
4. Glycogen Synthesis vs Degradation4. Glycogen Synthesis vs Degradation
![Page 29: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/29.jpg)
2929
UDP-Glucose is an activated form of glucose
UDP-Glucose is an activated form of glucose
4.1 UDP-Glucose4.1 UDP-Glucose
![Page 30: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/30.jpg)
3030
UDP-Glucose is an activated form of glucose
UDP-Glucose is an activated form of glucose
4.1 Glycogen Synthesis4.1 Glycogen Synthesis
![Page 31: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/31.jpg)
3131
4.2 Glycogen Synthase4.2 Glycogen Synthase
![Page 32: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/32.jpg)
3232
4.3 Branching Enzyme4.3 Branching Enzyme
![Page 33: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/33.jpg)
3333
4.3 Branching Enzyme4.3 Branching Enzyme
![Page 34: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/34.jpg)
3434
Glycogen Synthase is also regulated by phosphorylation
Protein kinase A catalyses the phosphorylationGlycogen synthase a is the more active, dephosphorylated formGlycogen synthase b is the less active, phosphorylated form
Glycogen Synthase is also regulated by phosphorylation
Protein kinase A catalyses the phosphorylationGlycogen synthase a is the more active, dephosphorylated formGlycogen synthase b is the less active, phosphorylated form
4.4 Regulation of Glycogen Synthase4.4 Regulation of Glycogen Synthase
![Page 35: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/35.jpg)
3535
Only 1 equivalent of ATP is used for storing each glucose unit
Only 1 equivalent of ATP is used for storing each glucose unit
4.5 Glycogen is an Efficient Storage Form of Glucose
4.5 Glycogen is an Efficient Storage Form of Glucose
![Page 36: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/36.jpg)
3636
Regulation by hormone triggered c-AMP cascade:
Regulation by hormone triggered c-AMP cascade:
5. Reciprocal Regulation ofSynthesis vs Breakdown
5. Reciprocal Regulation ofSynthesis vs Breakdown
![Page 37: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/37.jpg)
3737
PP1 reverses regulatory effects of kinases
PP1 dephosphorylatesglycogen phosphorylasephosphorylase kinaseglycogen synthase
PP1 reverses regulatory effects of kinases
PP1 dephosphorylatesglycogen phosphorylasephosphorylase kinaseglycogen synthase
5.1 Protein Phosphatase 15.1 Protein Phosphatase 1
![Page 38: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/38.jpg)
3838
PP1 is inactivated by the hormone-triggered c-AMP cascade
PP1 is inactivated by the hormone-triggered c-AMP cascade
5.1 Protein Phosphatase 15.1 Protein Phosphatase 1
![Page 39: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/39.jpg)
3939
The insulin-triggered tyrosine kinase cascade activates PP1
The insulin-triggered tyrosine kinase cascade activates PP1
5.2 Insulin Activates Protein Phophatase 1
5.2 Insulin Activates Protein Phophatase 1
![Page 40: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/40.jpg)
4040
Blood glucose levels regulate glycogen metabolism in the liver
Blood glucose levels regulate glycogen metabolism in the liver
5.3 Regulation by Blood Glucose 5.3 Regulation by Blood Glucose
![Page 41: Lecture 8 - Glycogen Metabolism](https://reader035.vdocuments.us/reader035/viewer/2022062301/56813e05550346895da7e3d8/html5/thumbnails/41.jpg)
4141
Glucose allosterically converts phosphorylase a from the R-state to the T-State
Glucose allosterically converts phosphorylase a from the R-state to the T-State
5.3 Regulation by Blood Glucose 5.3 Regulation by Blood Glucose