glycogenesis + hormonal stimulation

describe the structure of glycogen

• branched polymer

• multiple alpha-D-glucose units linked by alpha (1→4) glycosidic bonds

  • linear chains

• every 12-14 glucose residues = alpha (1→6) bond for branch point

advantages of branching

• more glucose units can be packed into glycogen structure

• prevents crystallization of glucose

which linkage connects the glucose in a linear chain in glycogen?

A) alpha (1→4) glycosidic bonds

B) beta (1→4) glycosidic bonds

C) alpha (1→6) glycosidic bonds

D) beta (1→6) glycosidic bonds

A) alpha (1→4) glycosidic bonds

which linkage forms the branch point in glycogen?

A) alpha (1→4) glycosidic bonds

B) beta (1→4) glycosidic bonds

C) alpha (1→6) glycosidic bonds

D) beta (1→6) glycosidic bonds

C) alpha (1→6) glycosidic bonds

open -OH group ends of glycogen chain are called _____

• nonreducing ends

the reducing end of glycogen is capped by ___

• glycogenin

  • protein

new glucose units are added at one end?

• non-reducing ends

  • 4 = existing

  • 1 = new glucose/incoming glucose

glycogenesis definition

• synthesis of glycogen from alpha-D-glucose

glycogenesis is a (catabolic/anabolic) process

• anabolic

functions of liver glycogen

• maintain blood glucose concentration

• increase in well-fed state

• decrease in the starvation state

muscle glycogen functions

• fuel reserve for ATP synthesis during exercise

• decreased levels due to strenuous muscle activity

• synthesized when glycogen stores are deposited

glycogenin

• priming glucosyltransferase

  • acceptor of glucose residues

• self-catalyzing

• forms initiating primer when a glucose unit is attached to its Tyr -OH group

initiating primer uses what AA?

• TYR (Y)

  • OH group on glycogenin

full steps of glycogenesis

1. glucose → (hexokinase) → glucose-6-phosphte

2. glucose-6-phosphate → (phosphoglucomutase) → glucose-1-phosphate

   • isomers

3. glucose-1-phosphate + UTP→ (UDP-glucose-pyrophosphorylase) → UDP-glucose (activated glucose)

4. form the initating primer (UDP-glucose-glycogenin)

5. chain elongation = transfer glucose units from UDP-glucose → (glycogen synthase) → glycogen

6. branching = 4:6 transferase → transfer 5-8 residues from non-reducing end to a different residue on chain → creates alpha-(1,6) linkage

transferring of glucose units occurs at the …

• nonreducing end

  • the reducing end = capped w/ glycogenin

glucose 6-phosphate is also found in …

• glycolysis

  • glucose → (hexokinase) → glucose 6-phosphate → (phosphoglucose isomerase) → fructose 6-phosphate

• Glucogenesis

  • fructose 6-phosphate → (phosphoglucose isomerase) → glucose 6-phosphate → (glucose 6-phosphatase) → D-glucose

conversion of glucose 6-phosphate to glucose 1-phosphate uses what enzyme?

• phosphoglucomutase

synthesis of UDP-glucose uses what enzyme?

• UDP-glucose pyrophosphorylase

synthesis of initiating primer uses what enzyme

• glycogenin

chain elongation is performed with what enzyme

• glycogen synthase

formation of branches (1,6 branches, extension of 1,4 branched chains) is performed by what enzyme

• 4:6 transferase

4:6 transferase

creates branching point with alpha (1→6) bonds

well-fed state: in the liver, glycogenesis is (accelerated/inhibited)

at rest: in the muscles, glycogenesis is (accelerated/inhibited)

• accelerated

regulation of glycogen metabolism occurs at what 2 levels

1. receptor

2. hormonal

glycogen phosphorylase (glycogenolysis) and glycogen synthase (glycogenesis) are hormonally regulated by what substances?

• insulin

• glucagon

• epinephrine/adrenaline

insulin promotes…

• glycogen synthesis

• glucose uptake

• hexokinase making glucose-6 (glycolysis)

• favors glycogen synthase

• inhibits glycogen phosphorylase

glucagon promotes..

• suppresses glycogen synthesis

• favors glycogen phosphorylase

epinephrine/adrenaline regulation of glycogen metabolism

• sympathetic NS /fight/flight

• increases glycogenolysis

insulin hormonal regulation steps

1. insulin binds to receptor to activate tyrosine kinase

2. tyrosine kinase phosphorylates insulin-sensitive kinase

3. insulin-sensitive kinase phosphorylates activated protein phosphatase-1 (PP-1)

4. PP-1 →

   • activates glycogen synthase → glycogen synthesis

   • inhibits phosphorylase kinase → prevents breakdown of glycogen (indirect inhibition of glycogen phosphorylase)

increases glucose in blood stream also increases/activates what enzymes?

• hexokinase → glycolysis

• glycogen synthase → glycogenesis

• increased GLUT4

dephosphorylated glycogen synthase is (active/inactive)

• active

phosphorylated glycogen synthase is (active/inactive)

• inactive

dephosphorylated glycogen phosphorylase is (active/inactive)

• inactive

phosphorylated glycogen phosphorylase is (active/inactive)

• actve

what enzyme is used for hormonal stimulation of glycogen synthesis?

• PP1 (activated protein phosphatase-1)

glycogen breakdown and glycogen synthesis is an example of ___

• reciprocal regulation