Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted...

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Dr. Phillip Carpenter medpathwaymcat Med-pathway [email protected] Glycogen Metabolism

Transcript of Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted...

Page 1: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

Dr. Phillip Carpenter

[email protected]

Glycogen Metabolism

Page 2: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

The Fed & Fasted States: Maintaining Glycemia

Page 3: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

The Fed & Fasted States

A.

B.

FASTED

FED

Page 4: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

G-6P & Glycogen synthesis

Page 5: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

UDP GlucoseGlycogen Synthase

UDP

PhosphorylasePi

+

CH2OH

OOH

O

HHO P O-

O-

O

CH2OH

OH

OH

CH2OH

OH

O

H

O

CH2OH

OH

O

H

O

CH2OH

OH

OH

CH2OH

OH

O O RHO

HOO R

CH2OH

OH

OH

CH2OH

OH

O

H

O O RHO

O

H

Glycogen Metabolism

H

1 4 14

65

3 2

Page 6: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

1

4 16

1 41

4

Glycogen Branching

Branching & DebranchingEnzymes

Page 7: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

O

CH2OH

OH

OH

H

H

HO

Glucoseαê

14

Acetal

Hemiacetal

CH2OH

OH

OHH

OH4

H

1

Glucose

α 1, 4 glucose

Glycosidic Linkages

Page 8: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

CCC

C

CH2OH

C

OHOH

OH

HO

O

HH

HH

H

..

α-D-Glucose (35 %)

β-D-Glucose (65 %)

CH2OH

OHOH

OHHO

14

CH2OHOH

OH

OHHO

14

Anomericcarbon

D Configuration

....

CH2OH

OH H

H

OHH

HOHO

H

O

Hemiacetal

1

23

45

6

H

....

CH2OH

OH OH

H

HH

HOHO

H

O

Equatorial

Axial

Fischer structure Haworth projection Chair conformation

1

4

23

3

5

6

β-D-Glucose (65 %)

α-D-Glucose (35 %)

Mutarotation

Page 9: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

Reducing Sugars

Glucose is an aldose

Reducing Sugars

Reducing Ends

Page 10: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

Glycogen SynthesisMultiple Tissues

Page 11: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

Glycogen SynthesisMultiple Tissues

Page 12: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

Glycogen N + 2 ATP→ Glycogen N + 1 + 2 ADP + 2 Pi.

Glycogen SynthesisMultiple Tissues

Page 13: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

Glycogen N + 2 ATP→ Glycogen N + 1 + 2 ADP + 2 Pi.

Glycogen SynthesisMultiple Tissues

Irreversible

Endergonic

Page 14: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

Glycogen Synthesis

Page 16: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

By Wanderley Souza - Kinetoplastid Biology and Disease "From the cell biology to the development of new chemotherapeutic approaches against trypanosomatids:dreams and reality" Figure 17, Public Domain, https://commons.wikimedia.org/w/index.php?curid=22764768

Glycogen granules

Page 17: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

Miquel, J., Vilavella, D., Swiderski, Z., Shimalov, V. V. & Torres, J. 2013: Spermatological characteristics of Pleurogenidae (Digenea) inferred from the ultrastructural study of Pleurogenes claviger, Pleurogenoidesmedians and Prosotocus confusus. Parasite, 20, 28. doi:10.1051/parasite/2013028

Glycogen Granules & Glycosome

Page 18: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

Glycogen Metabolism

PPi

Page 19: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

EPINEPHRINE GLUCAGON

cyclaseATP

GDP7TM receptor

Liver

cAMP

GTP

(LIVER)

Page 20: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

EPINEPHRINE GLUCAGON

cyclaseATP

GTP

GDP7TM receptor

Liver

cAMP

cAMP AMP

PhosphodiesteraseAdenylyl cyclase

Page 21: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

EPINEPHRINE GLUCAGON

cyclaseATP

GTP

GDP

PhosphorylaseKinase

7TM receptor

Liver

P

cAMP

PKA

GlycogenSynthase

P

Page 22: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

EPINEPHRINE GLUCAGON

cyclaseATP

GTP

GDP

PhosphorylaseKinase

7TM receptor

Liver

P

PPhosphorylase

cAMP

PKA

Page 23: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

EPINEPHRINE GLUCAGON

cyclaseATP

GTP

GDP

PhosphorylaseKinase

7TM receptor

Liver

P

PPhosphorylase

cAMP

PKA

Page 24: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

CH2OH

OH

OHHO

CH2OH

O

OH

OHO

EPINEPHRINE GLUCAGON

cyclaseATP

GTP

GDP

CH2OH

OH

OHHO

O P

O

O-

O-

β-D-Glucose 1-P

PhosphorylaseKinase

7TM receptor

Liver

P

PPhosphorylase

cAMP

PKA

Pi

R

Page 25: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

CH2OH

OH

OHHO

CH2OH

O

OH

OH

O

EPINEPHRINE GLUCAGON

cyclaseATP

GTP

GDP

CH2OH

OH

OHHO

O P

O

O-

O-

CH2O-P

OH

OH

OHHO

β-D-Glucose 1-P

β-D-Glucose 6-P

PhosphorylaseKinase

7TM receptor

Liver

P

PPhosphorylase

cAMP

PKA

Pi

R

Page 26: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

CH2OH

OH

OHHO

CH2OH

O

OH

OH

O

EPINEPHRINE GLUCAGON

cyclaseATP

GTP

GDP

CH2OH

OH

OHHO

O P

O

O-

O-

CH2OH

OH

OHHO

OH

CH2O-P

OH

OH

OHHO

β-D-Glucose 1-P

β-D-Glucose 6-P

β-D-Glucose

Pi

H2O

PhosphorylaseKinase

7TM receptor

Liver

P

PPhosphorylase

cAMP

PKA

Pi

R

Glucose 6-phosphatase

Page 27: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

CH2OH

OH

OHHO

CH2OH

O

OH

OH

O

EPINEPHRINE GLUCAGON

cyclaseATP

GTP

GDP

CH2OH

OH

OHHO

O P

O

O-

O-

CH2OH

OH

OHHO

OH

CH2O-P

OH

OH

OHHO

β-D-Glucose 1-P

β-D-Glucose 6-P

β-D-Glucose

Pi

H2O

Glucose

PhosphorylaseKinase

7TM receptor

Liver

P

PPhosphorylase

cAMP

PKA

Pi

R

Glucose 6-phosphatase(LIVER)

Page 28: Glycogen Metabolism - Med-Pathway · 2020. 11. 20. · Glycogen Metabolism. The Fed & Fasted States: Maintaining Glycemia. The Fed & Fasted States A. B. FASTED FED. G-6P & Glycogen

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