Glygocen, Gluconeogenesis and the HMP Shunt Flashcards Preview

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Flashcards in Glygocen, Gluconeogenesis and the HMP Shunt Deck (81)
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1

Glycogen metabolism occurs in the

cytoplasm

2

the rate-limiting enzymes of glycogen metabolism are

1. glycogen synthesis: glycogen synthase
- activated by insulin in liver and muscle
2. Glycogenolysis: glycogen phosphorylase
- activated by glucagon in liver (hypoglycemia)
- activated by epinephrine and AMP in skeletal muscle (exercise)
- a phosphorylase breaks bonds using Pi rather than H20

3

Glucose 6 phosphate releases free glucose. Where is it found?

- Glucose 6P is only found in the liver
- involved in glycogen metabolism

4

Glucose Deficiencies:

- G6PD
- Hepatic glycogen phosphorylase deficiency
- muscle glycogen phosphorylase deficiency
- lysosomal alpha 1,4-glucosidase deficiency

5

Where does gluconeogenesis occur?

- the cytoplasm and the mitochondria
- predominantly in the liver

6

- What is the rate-limiting enzyme of glycogenolysis?
- What is it activated by?

- glycogen phosphorylase
- activated by glucagon in liver (hypoglycemia)
- activated by epinephrine and AMP in skeletal muscle (exercise)

7

What is the controlled enzyme of gluconeogenesis?

1. Fructose 1,6 bisphosphatase
- in the cytoplasm
- activated by ATP
- inhibited by AMP and fructose 2,6-bisP
- Insulin (inhibits) and glucagon (activates) by their control of PFK-2 (produces Fructose 2,6-BP)

8

Pyruvate Carboxylase

- involved in gluconeogenesis
- activated by acetyl CoA from beta-oxidation
- biotin
- in the mitochondria

9

Phosphoenolpyruvate carboxykinase (PEPCK)

- involved in gluconeogenesis
- in the cytoplasm
- induced by glucagon and cortisol

10

- What is the rate-limiting enzyme of glycogen synthesis?
- What is it activated by?

- glycogen synthase
- activated by insulin in liver and muscle

11

Glucose 6-Phosphatase (Endoplasmic Reticulum)

- only in the liver
- involved in gluconeogenesis
- required to release free glucose from tissue

12

Where does the Hexose Monophosphate Shunt occur?

in the cytoplasm of most cells

13

What are the functions of the Hexose Monophosphate Shunt?

- generates NADPH
- produces sugars for biosynthesis (ribose 5P for nucleotides)

14

What are the rate-limiting enzymes of the HMP?

1. Glucose 6 Phosphate Dehydrogenase
- inhibited by NADPH
- induced by insulin in liver

15

G6PD deficiency

- episodic hemolytic anemia (MC) induced by infection and drugs
- chronic hemolysis, CGD-like symptoms (very rare)
- heinz bodies are characteristic
- X-linked

16

Glycogen synthesis and degradation occur primarily in

- the liver and skeletal muscle,
- although other tissues (including cardiac muscle and the kidney) store smaller quantities

17

- Glycogen is stored in the ____
- as either ______ or ______

Glycogen is stored in the cytoplasm as either:
- single granules (skeletal muscle) or
- clusters of granules (liver)

18

in white muscle fibers, the glucose is converted primarily to

lactate
- white muscle fibers are "fast-twitch"
- in red (slow-twitch) muscle fibers the glucose is completely oxidized

19

- Synthesis of glycogen granules begins with a core of
- glucose addition to the granule begins with
- steps of glycogen metabolism

- core protein glycogenin
- glucose addition to the granule begins with Glucose 6P
- which is converted to Glucose 1P and
- activated to UDP-glucose for addition to the glycogen chain by glycogen synthase
- glycogen synthase is the rate-limiting enzyme of glycogen synthesis

20

- Glycogen Synthase in the liver is activated by
- is inhibited by

- insulin
- glucagon and epinephrine

21

Step 1 of Glycogen Metabolism

- Glucose is converted to Glucose 6P by Glucokinase
- phosphorylating Glucose traps it in the cell
- this occurs in the liver

22

Step 2 of Glycogen Metabolism

- Glucose 6P is converted to Glucose 1P by a mutase

23

- Glycogen Synthase in skeletal muscle is activated by
- is inhibited by

- insulin
- epinephrine

24

Glucose 1P is converted to

Glucose 1P is converted to UDP-Glucose

25

Glycogen is converted back to Glucose 1P by

- glycogen phosphorylase (and debranching enzyme)
- Glucagon stimulates in liver
- epinephrine stimulates in liver and muscle
- AMP stimulates in muscle
- Glycogen phosphorylase is active when PHOSPHORYLATED
- Glucagon binds to g-protein coupled receptor --> cAMP --> activates kinase --> phosphorylates glycogen phosphorylase

26

UDP-Glucose is added to the growing chain by

- Glycogen synthase (and branching enzyme)
- rate-limiting step in glycogen metabolism
- active when DE-phosphorylated
- activated by insulin in liver and muscle
- Glucagon inhibits (in liver): (Glucagon binds to g-protein coupled receptor --> cAMP --> kinase activated --> glycogen synthase phosphorylated and thus, deactivated

27

How does Glucagon inhibit glycogen synthase in the liver?

- Glycogen Synthase is active when de-phosphorylated
- Glucagon binds to g-protein coupled receptor --> cAMP --> activates kinase --> glycogen synthase phosphorylated and thus, deactivated

28

How does Glycogen Synthase work?

1. glycogen synthase forms a linear alpha 1,4 glycosidic polyglucose chain
2. branching enzyme hydrolyzes an alpha 1,4 bond to release a block of oligoglucose
3. branching enzyme transfers that unit to a different location and attaches it with an alpha 1,6 bond (to create a branch)
4. Glycogen synthase extends both branches

29

How is Glycogen phosphorylase controlled?

- Glycogen phosphorylase is active when PHOSPHORYLATED
- Glucagon binds to g-protein coupled receptor --> cAMP --> activates kinase --> phosphorylates glycogen phosphorylase
- Glucose 1P is converted back to Glucose 6P by a mutate
- GLucose 6P is converted to Glucose by Glucose 6-Phosphatase (found in the liver)

30

How does Glucagon stimulate glycogenolysis in the liver?

- glycogen phosphorylase (and debranching enzyme) convert Glycogen back to Glucose 1P
- a phosphorylase breaks bonds using Pi rather than H20
- Glycogen phosphorylase breaks alpha 1,4 bonds, releasing Glucose 1P from the periphery of the granule.
- can't break alpha 1,6 bonds, so it stops when it reaches the outermost branch points