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Flashcards in glycogen Deck (72):
1

What is the only organ that can make glucose?

liver

2

what is the preferred energy source for the brain and required for RBCs?

glucose

3

constant levels of blood glucose

absolute requirement

4

what is essential for exercising muscle?

glucose

5

Where is glucose obtained from?

1. diet
2. GNG (fasting)
3. Glycogen stores (quick energy)

6

Acetyl CoA

CANNOT make glucose

7

dietary intake of glucose

-sporadic
-dependent on the diet content
-not always reliable source of blood glucose

8

GNG and glucose

-can provide sustained synthesis of glucose
-BUT it is somewhat slow in responding to a falling blood glucose levels

9

glycogen and glucose

-mechanisms for storing a supply of glucose in a rapidly mobilizable form

10

glycogen tissue distribution

-virtually any cell in the body may contain glycogen (high levels can be damaging)

11

Main stores of glycogen

skeletal muscle
liver

12

glycogen in skeletal muscle

-for its own use as a fuel source
-Can never exit skeletal muscle
-400g
-1-2% fresh weight of resting muscle

13

glycogen in liver

-maintain blood glucose during early fasting
-goal is to be released to maintain blood glucose levels
-100g
-10% of fresh weight of an adult well-fed liver

14

hepatocytes

will contain more glycogen than skeletal muscle

15

glycogen storage diseases

amount of glycogen stored in liver and skeletal muscle can be significantly higher or lower

16

absence of glucose

-glycogen is degraded to glucose and it rapidly released from liver and kidney glycogen
-muscle glycogen is extensively degraded in exercising muscle to provide that tissue with an important energy source

17

as glycogen stores are depleted

the synthesis of glucose (gluconeogenesis) takes over, therefore glycogen serves as a glucose source in the gap between the fall of blood glucose hours after a meal and the onset of gluconeogenesis which needs time to kick in and occurs a few hours later

18

glycogen structure

-branched chain polysaccharide made from a-D-glucose (linear)
-10-40x10^3 glucose molecules in 1 glycogen granule
-primary glycosidic bond is a(1,4) linkage
-branch containing a(1,6) linkage every 8-10 glucose residues

19

discrete cytoplasmic granules (B-particles)

large molecules of glycogen
-associated with the enzymes necessary for the synthesis and degradation

20

glycogenesis

synthesis of glycogen

21

step 1 of glycogensis

synthesis of uridine diphosphate glucose

22

step1: synthesis of uridine diphosphate glucose

-a-D-glucose goes to glucose 6-P with enzyme hexo/glucokinase
-glucose 6-P goes to glucose 1-P with enzyme phosphoglucomutase
-UTP cleaves a phosphate and becomes UDP glucose
-highly endergonic

23

What does hexo/glucokinase do to a-D glucose

turns it to glucose 6-P and traps it in the cell

24

What drives the synthesis of UDP?

that fact that it's highly exergonic

25

step 2 of glycogenesis

synthesis of a primer to initiate glycogen synthesis

26

glycogen synthase

-CAN NOT add UDP glucose to a single glucose molecules
-It can ONLY ELONGATE existing glycogen molecules (primers)

27

if no glycogen primers are available

-protein glycogenin serves as a primer
-specific Tyr residue serves as attachment point for glycogen synthase
-glycogenin itself catalyzes this attachment reaction and the attachment of next few UDP-glucose molecules via a(1,4) glycosidic bond

28

step 3 of glycogenesis

elongation of glycogen chains

29

step 3: elongation of glycogen chains

-enzyme: glycogen synthase

30

glycogen synthase

-elongates the existing glycogen primers
-transfer UDP-glucose to the non-reducing end of the primer
-forms a(1,4) glycosidic bonds ONLY between C-1 of UDP glucose and C-4 from the primer
-rate limiting enzyme

31

What bonds does glycogen synthase form?

a(1,4) glycosidic bonds ONLY between C-1 of UDP glucose and C4 from the primer

32

What kind of bonds does glycogenic form between the UDP glucose molecules?

a(1,4)glycosidic bonds

33

What is the primary glycosidic bond of glycogen?

a(1,4) linkage

34

What type of bond is there every 8-10 glucose residues on glycogen?

branch containing a(1,6) linkage

35

step 4 of glycogenisis

formation of branches

36

Step 4: formation of branches

-enzyme: branching enzyme (amylo...)
-removes a chain of 6-8 glucose residues from the end of the glycogen chain (breaks an a(1,4) bond)
-attaches it to an non-terminal glucose residue by an a(1,6) bond
-functions as a 4:6 transferase

37

What does the branching enzyme function as?

4:6 transferase

38

degradation of glycogen (glycogenolysis)

-NOT a simple reversal of the glycogenesis
-separate set of enzymes
-4-step pathway

39

4 step pathway of glycogenolysis

1. shortening of chains
2. removal of branches
3. conversion of glucose 1-P to glucose 6-P
4. conversion of glucose-6-P to glucose (LIVER ONLY)

40

step 1 of glycogenolysis

shortening of the chains

41

shortening of the chains

-step 1 of glycogenolysis
-enzyme glycogen phosphorylase

42

glycogen phosphorylase

-step 1 of glycogenolysis
-rate limiting regulatory step
-tissue specific isoforms: liver, brain, muscle
-sequentially cleaves a(1,4) glycosidic bonds from the ends of the glycogen chains
-uses inorganic Pi to cleave the bond and simultaneously attaches it to the glucose
-yields glucose 1-P
-stops when the chain has been shortened to 4 remaining glucosyl units from a branch point
-Requires PLP (derived from it B6) as a coenzyme

43

limit dextrins

-shortening of chains for glycogenolysis stops here.
-4 remaining glucosyl units
-cannot fit very well with the active center of enzyme at this point

44

Step 2 of glycogenolysis

removal of branches
enyme is debranching enzyme

45

debranching enzyme

-removal of branches
-single protein with 2 activities (2 different active sites)
-4:4 transferase activity
-1:6 glucosidase activity

(HAPPEN SIMULTANEOUSLY)

46

4:4 transferase activity of debranching enzyme

-removes 3 of the 4 glucosyl residues at the end of a chain breaking an a (1,4) bond
-transfers them to the end of another chain creating an a(1,4) linkage

47

1:6 glucosidase activity of debranching enzyme

-removes the remaining single glucose residue attached via a(1,6) linkage at the branch point
-yields free glucose (no Pi)

48

Step 3 og glycogenolysis

conversion of glucose 1-P to glucose 6-P
enzyme is phosphoglucomutase

49

phosphoglucomutase

-enzyme for conversion of glucose 1-P to glucose 6-P
-forms intermediate glucose-1,6-bisP
-activated by glucose 1-6-bis-P
-modified by Ser-phosphorylation at the catalytic site

50

step 4 of glycogenolysis

-dephosphorylation of glucose 6-P to glucose
-enzyme is glucose 6-phosphatase

51

glucose 6-Phosphatase

-dephosphorylation of glucose 6-P to glucose
-expressed in liver and kidney cortex
-expressed lesser in the pancreatic B-cells and intestinal mucosa
-ER transmembrane protein with active sites facing ER lumen
-a complex of multiple component proteins

52

glucose 6-Phosphatase complex

-complex of multiple component proteins
-3 transporters: G6PT1, 2, 3
-catalytic subunit- G6Pase-a-B

53

degradation of glycogen in the lysosomes

-lysosomal a(1,4)-glucosidase
-product of housekeeping gene
-regulated at the level of protein expression
-optimal pH=4.5
-only about 1-3% of the glycogen
-purpose of this pathway not well understood

54

regulation of glycogenesis in tissues

liver- in well fed state
muscle- begins at rest

55

regulation of glycogenolysis in tissues

liver-during fasting
muscle- during exercise

56

What are regulatory enzymes of glycogenesis and glcogenolysis?

glycogen synthase and glycogen phosphorylase

57

how is enzyme regulation in glycogenesis and glycogenolysis accomplished at 2 levels?

1. hormonal regulation to meet the needs of the body as a whole
2. Allosteric regulation to meet the needs of the particular tissue

58

What is glycogen phosphorylase activated by in the liver?

hormonal
-epinephrine
-glucagon

Allosterically
-none

59

what is glycogen phosphorylase activated by in the muscle?

homronal
-epinephrine

allosterically
-AMP
-Ca2+

60

What is glycogen phosphorylase inhibited by in the liver?

hormonal
-insulin

allosterically
-glucose 6-P
-glucose
-ATP

61

What is glycogen phosphorylase inhibited by in the muscle?

hormonal
-Insulin

allosterically
-Glucose 6-P
-ATP

62

What is glycogen synthase activated by in the liver?

hormona
-insulin

allosterically
-glucose 6-P

63

What is glycogen synthase activated by in the muscle?

hormonal
-insulin

allosterically
-glucose 6-P

64

What is glycogen synthase inhibited by in the liver?

hormonal
-glucagon
-epinephrine

allosterically
-none

65

What is glycogen synthase inhibited by in the muscle?

hormonal
-epinephrine

allosterically
-none

66

Why are branches important?

-increases solubility
-increases surface area
-more enzymes
-faster degradation
-more nonreducing ends for faster synthesis and degradation

67

Von Gierke

deficient enzyme
-glucose 6-phosphatase (liver, kidney)

clinical features
-severe fasting hypoglycemia
-lactic acidosis
-hepatomegaly
-hyperlipidemia
-hyperurecemia
-short stature

glycogen structure
-normal

68

Pompe

deficient enzyme
-lysosomal a(1-4)-glucosidase

clinical features
-cardiomegaly
-muscle weakness
-death by 2 years

Glycogen structure
-glycogen-like material in inclusions

69

Cori

deficient enzyme
-debranching enzyme

clinical features
-mild hypoglycemia
-liver enlargement

glycogen structure
-short outer branches, single glucose residue at outer branch

70

Anderson

deficient enzyme
-branching enzyme

clinical features
-infantile hypotonia
-cirrhosis
-death by 2 years
-rare

glycogen structure
-very few branches, especially towards periphery

71

McArdle

deficient enzyme
-muscle glycogen phophorylase

clinical features
-muscle cramps and weakness on exercise
-myoglobinuria

glycogen structure
-normal

72

Hers

deficient enzyme
-hepatic glycogen phophorylase

clinical features
-mild fasting hypoglycemia
-hepatomegaly
-cirrhosis

glycogen structure
-normal