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dmd 5241 > glycogenesis and glycogenolysis > Flashcards

glycogenesis and glycogenolysis Flashcards

1
Q

when is glycogen formed in the liver?

A

after a meal

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2
Q

between meals, what does the glycogen from the liver do?

A

provides an immediate source of glucose for maintenance of of blood glucose levels or during vigorous exercise when the use of blood glucose increases by the muscles

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3
Q

what does glycogen do in skeletal muscles and other tissues?

A

skeletal
- important fuel source when energy demands are high

other cell types
- small stores of glycogen also serve as an emergency fuel source for generating ATP when oxygen supply or blood flow is restricted

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4
Q

how much glycogen is found in the liver and muscles?

A

100g and 400g, respectively

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5
Q

what does insulin insensitive mean?

A

if a tissue is insulin insensitive, it means they do not require insulin for glucose uptake

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6
Q

can an insulin insensitive tissue be effected by insulin? if so, how?

A

yes. glucose transport in some insulin insensitive cells increases in the presence of insulin

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7
Q

which cells are insulin sensitive? insulin insensitive?

A

sensitive
- most tissues (adipose, muscle)

insensitive

  • erythrocytes
  • leukocytes
  • lens of eye
  • cornea
  • LIVER
  • brain
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8
Q

is the liver insulin sensitive or insensitive?

A

the liver is insulin insensitive

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9
Q

what happens to insulin levels after a carbohydrate meal?

A

after a carbohydrate meal:

  • blood glucose rises
  • rise in blood glucose causes a RISE in insulin secretion
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10
Q

what happens as insulin binds to cell membrane receptors?

A

insulin binds to cell membrane receptors and GLUT 4 from intracellular vesicles move to the cell membrane

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11
Q

what GLUT moves to the cell membrane after a meal and why?

A
  • GLUT 4 moves to cell membrane

- this allows more glucose to enter the cell and as a result, blood glucose levels drop

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12
Q

failure of glucose transport is a major characteristic of what?

A

diabetes

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13
Q

what is a direct result of insulin-stimulated translocation of GLUT-4?

A

this will result in activation of protein kinase B (PKB)

pkb phosphorylates proteins involved in GLUT-4 translocation

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14
Q

between meals, what happens to insulin levels?

A

decline

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15
Q

what does muscle contraction require?

A

glucose uptake for the generation of energy

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16
Q

what stimulates glucose uptake by the muscles between meals?

A

increase in AMP levels and the subsequent (after) activation of AMP-stimulated protein kinase (AMPK)

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17
Q

what does AMPK activation do in muscle cells?

A

AMPK activation promotes the translocation of GLUT-4 transporters to muscle membrane

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18
Q

what 2 things will promote translocation of GLUT 4 transporters?

A
  • AMPK activation (a result of increased AMP levels)

- insulin binding to cell membranes

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19
Q

where is AMP generated?

A

in the adenylate kinase reaction

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20
Q

when does glycogenesis begin (what event)?

A

the transfer of the terminal phosphate group from ATP to the hydroxyl group in C-6 of glucose to form glucose-6-phosphate

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21
Q

what reaction is common to all pathways that utilize glucose?

what pathways utilize glucose this way?

A

the transfer of a phosphate to glucose to form glucose-6-phosphate

  • glycogenolysis
  • glycolysis
  • pentose phosphate pathway
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22
Q

what is significant about the phosphorylation of glucose?

A

glucose-6-P cannot pass through the cell membrane to the extracellular side, keeping it within the cell and committed to further metabolism

  • cannot pass back because it is not a substrate for the glucose transporters
23
Q

describe hexokinase

  • km to glucose (and what this means)
  • type of enzyme
  • what tissues
  • inhibited or not by product (G6P)
A

hexokinase:

  • 0.2 mM Km, meaning it has a high affinity for glucose
  • constitutive enzyme (produced by cell under all conditions)
  • in tissues in general
  • INHIBITED by G6P
24
Q

describe glucokinase

  • km to glucose (and what this means)
  • type of enzyme
  • what tissues
  • inhibited or not by product (G6P)
A

glucokinase

  • 10 mM Km, meaning it has a low affinity for glucose
  • induced enzyme (stimulated by an inducer)
  • in the liver and pancreatic beta cells
  • NOT inhibited by G6P
25
Q

what cells contain glucokinase?

A
  • liver cells

- pancreatic beta cells

26
Q

why is the km for glucose high in the liver and GLUT 2?

A

so glucose can be phosphorylated after its concentration rises in the portal blood

27
Q

in the liver, what is the rate of glucose phosphorylation dependent upon

A

the level of activity of glucokinase

28
Q

in the fasting state, where is glucokinase located? what is it bound to?

A
  • in the hepatocyte nucleus

- bound to glucokinase regulating protein

29
Q

when bound to GKRP, is GK active or inactive?

A

inactive

30
Q

what releases GK from GKRP?

what does it do upon release?

A
  • glucose concentrations rise in the cytoplasm and nucleus
    • after a carb meal
  • fructose-1-P will also release GK from the GKRP
  • travels to cytoplasm and phosphorylates glucose
31
Q

where is dietary fructose metabolized? what does it become? what effect does the product have on GK?

A
  • metabolized rapidly in the liver to form fructose-1-P

- causes GK to release from GKRP

32
Q

compare the effects of fructose-6-P and fructose-1-P on GK

A

fructose-6-P: favors translocation of GK into the nucleus to BIND to GKRP (inhibits GK activity)

fructose-1-P: causes dissociation of GK from GKRP (promotes GK activity)

33
Q

what is glycogenesis?

A

the formation of glycogen from sugar

34
Q

what is the starting molecule of glycogenesis? from what and where is it formed? name the enzyme in the process

A
  • glucose-6-phosphate
  • formed from glucose in the liver
  • hexokinase
35
Q

name the enzyme that isomerizes G6P to G1P

A

phosphoglucomutase

36
Q

is G6P to G1P a reversible reaction

A

yes, it is an isomerization

37
Q

what 2 molecules form UDP-glucose? name the enzyme involved in this reaction

what simultaneously happens in this reaction?

A
  • G1P and UTP form UDP-glucose
  • enzyme: UDP-glucose phosphoglucomutase
  • pyrophosphate is simultaneously released in this reaction
38
Q

what is the fate of the pyrophosphate (PPi)?

A

hydrolyzed to yield two molecules of inorganic phosphate (Pi)

39
Q

describe the function of glycogen synthase

A
  • transfers the glucose moiety of UDP-glucose to nonreducing end of preexisting glycogen primer molecule
  • this enlarges the polysaccharide by one glucose unit
  • at the same time, UDP is liberated
40
Q

what happens when there is no glycogen fragment for glycogen synthase to add to?

A

glycogenin will serve as an acceptor of the glucose unit

41
Q

what is glycogenin?

A
  • dimer
  • accepts glucose from glycogen synthase when there is no glycogen fragment
  • will accept a few molecules of glucose
  • stays associated with completed glycogen molecule
42
Q

what performs the addition of a glucose molecule into glycogenin?

A

glycogenin performs the addition itself (autoglucosylation)

43
Q

what transfers the terminal phosphoryl from ATP to UDP?

A

nucleoside diphosphokinase

44
Q

what is the purpose of nucleoside diphosphokinase?

A
  • to transfer the terminal phosphoryl group from ATP to UDP

- this regenerates UTP

45
Q

what are the 2 catalytic activities of the debranching enzyme?

A
  • acts as a transferase by removing 3 glucose residues and adding it to a larger chain
  • hydrolyze the remaining residue at the 1,6 branch by the alpha-1,6-glucosidase, resulting in release of a free glucose molecule
46
Q

what is the ultimate action/purpose of the debranching enzyme?

A
  • convert the branched structure to a linear one
47
Q

what type of bond adds the 3 residues to the end of a larger chain (as performed by the debranching enzyme)

A
  • alpha-1,4
48
Q

what does the alpha-1,6-glucosidase of the debranching enzyme do?

A

hydrolyzes the remaining glucose molecule at the 1,6 branch

49
Q

what is the function of phosphoglucomutase?

A

isomerizes G1P G6P

50
Q

what are the fates of G1P?

A
  • hydrolyzed to glucose

or

  • enter another metabolic pathway
51
Q

where does hydrolysis of the liver take place? what enzyme does this?

A
  • takes place in the liver

- the enzyme is glucose-6-phosphatase

52
Q

do muscles contain G6P phosphatase?

A

heck no.

G6P phosphatase is only found in the liver

53
Q

what is the significance of muscles not containing G6P phosphatase?

A
  • G6P phosphatase is what converts glucose-6-phosphate to glucose
  • because G6P phosphatase is not in the muscles, when G6P enters the muscle it is therefore committed to glycolysis
  • by being committed to glycolysis, it will provide energy for muscle contraction

dmd 5241 (3 decks)

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