glycogen. human liver - 50 g/kg wet wt. skeletal muscle - 15 g/kg wet wt. glycogenin = protein core...

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Glycogen

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Page 1: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~

Glycogen

Page 2: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~

Human liver - 50 g/kg wet wt.

Skeletal muscle - 15 g/kg wet wt.

Glycogenin = protein core

Glycosome

~

~

Page 3: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~

1-4 bonds1-6 bonds

Glycoside bonds

Page 4: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~
Page 5: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~

Proglycogen (acid insoluble)

Macroglycogen (acid soluble)

Size = glycogenin – Proglycogen – Macroglycogen

12 tiers is the maximum – branches too dense to allow GS

Tier 8

Page 6: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~

Lomako, et al., FASAB J. 9, 1126-1137, 1995

Macroglycogen

Proglycogen

Glygogenin

Two Forms of Muscle Glycogen

75% proglycogen/25% macroglycogen

Page 7: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~
Page 8: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~
Page 9: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~
Page 10: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~

Glycogen SynthesisGlycogen Synthase 1-4 bonds

Glycosyl 4:6 transferase

Branching enzyme(at least 11)

( leave at least 4)(move at least 7)

Page 11: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~
Page 12: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~

1-4 Bond1-6 Bond

Glycogenolysis

(Glucose-1-P Glucose-6-P)(phosphoglucomutase)

phosphorylaseGlucose -6-P

to glycolysis

glycosyl 4:4 transferase(breaks a 1-4, makes a 1-4)

(NEXT)

a b c

fed

a b c

Page 13: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~

a b c fed

Glycogenolysis (cont.)

a b cto another chain

free glucose

Amylo 1:6 glucosidase

a b c

fed

glycosyl 4:4 transferase

a b c

free glucose

Page 14: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~
Page 15: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~
Page 16: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~
Page 17: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~
Page 18: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~

Glycogen Synthesis- the storage of glucose via glycogen formation

-Glycogen Synthase- enzyme responsible for making 1-4 bonds between glucose molecules

-Glycosyl 4:6 transferase- enzyme that breaks 1-4 bonds, and makes 1-6 bonds to allow for branching

Glycogenolysis- the break down of glycogen into glucose

Summary

Page 19: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~

Summary• Skeletal Muscle• Epi/N-Epi (beta

receptor) C-AMP Ca++ (actives

phosphorylase kinase• These will increase

activity of phosphorylase and decrease glycogen synthase

• Insulin PDE activity which

will decrease C-AMP PP-1 which will

increase the activity of GS and decrease the activity of phosphorylase

Page 20: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~

Three CHO-Loading Protocols:Two Depletion & One Taper

Saltin and Hermansen, Nut. Physical Activity, pp.32-46, 1967

Page 21: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~
Page 22: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~

Phosphorylates glycogen synthase

Page 23: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~

CA++ actives Phosphorylase Kinase at the start of exercise by 20x. Ca++ binds to gamma subunit of PK.

Phosphorylase Kinase activated via C-AMP and PKA. Phosphorylase kinase phosphorylates Phosphorylase at serine 14.

AMP allosterically actives Phosphorylase.

Page 24: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~

Active Inactive

- P

Insulin activates PP-1 and PDE (phosphodiesterase). This will decrease C-AMP and dephosphorylate proteins that were phosphorylated by PKA

Page 25: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~

Lomako, et. al.,FASAB 7:1386-1393

Order of Glycogen Resynthesis

Page 26: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~

Glycogen Storage Diseases

Type I: Von Gierke Disease; Glucose-6-phosphatase Defect

Hypoglycemia occurs due to defect of the final step of gluconeogenesis. This disease, affects only liver and renal tubule cells Decreased mobilization of glycogen produces hepatomegaly.

Type V: McArdle Disease; Skeletal Muscle Glycogen Phosphorylase Defect

Skeletal muscle is affected, whereas the liver enzyme is normal. Exercise capacity is greatly reduced, hypoglycemia during exercise There is no rise in blood lactate during strenuous exercise. Muscle contains a high level of glycogen with normal structure

Type VI: Hers Disease; Liver Glycogen Phosphorylase Defect

Liver is affected, whereas the skeletal muscle enzyme is normal. Marked hepatomegaly occurs due to a high level of glycogen with normal structure.. Following administration of glucagon, there is no increase in blood glucose.

Page 27: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~

Casey, et al., J.Physiol. 48(1): 265-271, 1995.

Rapid Phase – increased insulin sensitivity GLUT 4 from exercise

Slow Phase- dependent on insulin concentration

Page 28: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~

EFFECT of DETRAINING on MUSCLE GLYCOGEN CONCENTRATIONS

Costill, et., al., Med. Sci. Sports Exerc., 17(3):339-343, 1985.

60%80% 72%100%

Page 29: Glycogen. Human liver - 50 g/kg wet wt. Skeletal muscle - 15 g/kg wet wt. Glycogenin = protein core Glycosome ~ ~

Costill, et. al., J.A.P. 31(6): 834-838, 1971.

Muscle Glycogen During 3 days of Endurance Training and al Low-CHO vs High-CHO Diet