Chapter 16: Glycogen Metabolism and Gluconeogenesis Flashcards

1
Q

general mechanism of glycogen breakdown to glucose-6-phosphate

A

1) phospholysis of glycogen reducing end to yield glucose 1 phosphate via glycogenphosphorylase.
2) Glc-1-P to glc -6-p via phosphoglucomutase

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2
Q

____ enzyme transfers the 3 glucose molecules of the branch of glycogen to the main chain

A

transglycosylase

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3
Q

____ enzyme cleaves the one remaining glucose branching off the main glycogen chain

A

glycosidase

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4
Q

ATP difference between glc-6-P from glycogen to undergo glycolysis and glc-6-P from blood glucose to undergo glycolysis?

A

when glucose is broken down by mobilizing glycogen, 3 ATP is released, but when blood glucose is broken down, only 2 are released.

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5
Q

glycogen synthesis mechanism

A

1) glucose to g6p via glucokinase
2) g6p to g1p via phosphoglucomutase
3) G1p to UDPG via UDPG-pyrophosphatase, releases PPi
4) glc OF the UDPG attaches to glycogen chain via glycogen synthase, UDP released.

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6
Q

what is glycogenin?

A

protein containing 7 glucoses used as a glycogen primer, allows glycogen synthase to extend the glycogen chain

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7
Q

what enzyme makes the glycogen branches?

A

amylo (1,4 to 1,6) transglycosylase branching enzyme

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8
Q

how are the enzymes that break down and build up glycogen (glycogen phosphorylase and glycogen synthase) covalently regulated?

A

because glycogen phosphoylase exists in 2 FORMS. glycogen phosphoylase A, which is active and breaks glycogen down, and glycogen phosphoylase B, which is deactivated, and not phosphorylated, which does not break down glycogen.

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9
Q

how is glycogen phosphoylase phosphorylated to become active?

A

via phosphorylase kinase.

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10
Q

phosphorylase kinase exists in two forms, what are they?

A

phosphorylase kinase A= phoshorylated and activated, and can phosphorylate glycogen phosphorylase B, turning it into A, so it can break down glycogen.

phosphorylase kinaseB= not phosphorylated and deactivated.

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11
Q

What phosphorylates kinase a?

A

the hormone cascade system lol (PKA)

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12
Q

outline the hormone cascade system

A

1) when glucose is low, glucagon is dumped into blood stream
2) glucagon binds to liver receptror, and activates ADENYLATE KINASE, making cAMP
3) cAMP activates PKA
4) PKA phosphorylate phosphorylase kinase into A form, activating it
5) phosphorylase kinase A phosphorylates glycogen phosphorylase B into its A form, activating it.
6) glycogen phosphorylase A phorphorylates glucose on the glycogen chain, making glucose into glucose 1 phosphate, which ultimately becomes glucose in the blood.

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13
Q

how is glycogen breakdown allosterically controlled?

A

when glucose concentrations in the liver are high, exceess glucose binds to glycogen phosphorylase a (usually meant to break down glycogen), and deactivates it with the help of phosphorylase phosphatase, converting it into its unactive form, glycogen phosphorylase b, which stops glycogen breakdown

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14
Q

AMP ____ phosphorylase a, starting glycogen breakdown

A

activates phosphorylase A

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15
Q

ATP _____ phosphorylase A, stopping glycogen breakdown

A

inhibits

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16
Q

glycogen phosphorylase A gets ____ when phosphoprotein phosphatase 1 binds it

A

gets deactivated tp glycogen phosphorylase B

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17
Q

3 main functions of phosphoprotein phosphatase 1

A

1) deactivates glycogen phosphorylase A to B
2) activates glycogen synthase
3) deactivates phosphorylase kinase A to B

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18
Q

what happens to glycogen synthase when it is phosphorylated?

A

it turns off, glycogen synthesis stops

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19
Q

glycogen synthase is activated via _____ and deactivated via_____

A

glycogen synthase is activated by phosphoprotein phosphatase 1, which de phosphorylates it, allowing it to conduct glycogen synthesis.

glycogen synthase is deactivated via glycogen synthase kinase/phosphorylase kinase a /or PKA , when it phosphorylates it. glycogen synthesis is stopped

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20
Q

how is glycogen synthase allosterically activated?

A

by excess glucose and glucose 6 phosphate, as well as insulin, which turns on protein kinase B, which turns off glycogen synthase Kinase/PKA/phosphorylase kinase a, reactivating glycogen synthase.

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21
Q

how is glycogen synthase allosterically deactivated/

A

via glucagon signal (hungry signal)

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22
Q

gluconeogenesis

A

making glucose from non-carbohydrates, like lactate, AA, glycerol

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23
Q

How is pyruvate turned into pep? where does this occur?

A

pyruvate and CO2 turns to oxaloacetate via pyruvate carboxylase. oxaloacetate combines with GTP to form PEP and CO2 via PEPcarboxykinase. occurs in the mitochondria

24
Q

in gluconeogenesis, fructose 1-6bp turns to fructose 6 phosphate via _____, a Pi is released.

A

fructose bisphosphate1, utilizes water

25
Q

in gluconeogenesis, glucose 6 phosphate is converted to glucose via _____ through a ____ process

A

glucose-6-phosphatase, utilizes water

26
Q

T/F, you need NADH to run gluconeogenesis

A

true, to facilitate the reverse-glycolysis reactions.

27
Q

how is NADH to power gluconeogenesis (in the cytosol) made if glycolysis is not running?

A

depends on type of molecule being used to make glucose.

If lactate: converts lactate to pyruvate via lactate dehydrogenase, and make NADH (because the fwd reaction mades NAD+)

if pyruvate: need to transport NADH from the mitochondria using malate asparatate shuttle system

28
Q

how much ATP does gluconeogenesis require?

A

4

29
Q

does anabolism require more energy than catabolism?

A

yes. it takes more energy to build glucose than it does to break it down

30
Q

PFK-1 is ____ by fructose-2,6 bi phosphate, and FBP-1 is _____ by fructose 2-6 bi phosphate

A

PFK-1 is activated by fructose 2,6 biphosphate, activating glycolysis and FBP-1 is deactivated by fructose 2,6 biphosphate, deactivating gluconeogenesis

31
Q

how is fructose 26 biphosphate regulated?

A

by PFK2(forms fru26bp) and by FBP2 (degradation of fru26bp back to fru6phosphate)

32
Q

activation pathway of PFK1 using fructose 26bisphosphate

A

PFK2 gets activated via covalent modification,and forms fru26bp, which activates PFK1, starting glycolysis

33
Q

is PFK 2 and FBP2 on the same protein?

A

yes

34
Q

how does glucagon regulate fructose 26 bisphosphate?

A

glucagon creates an increase in cAMP, which phosphorylates PFK2 deactivating it, which deactivates fructose 26bisphosphate (no glycolysis) but ACTIVATING FBP2, starting gluconeogenesis

35
Q

how does insulin regulate fructose 26 bisphosphate?

A

insulin deactivates FBP2, stopping gluconeogenesis because FBP2 degrades fru-26bisphosphate, and activates PFK-2, starting glycolysis, because PFK-2 increases the fru26biphosphate, which activates PFK1, which activates glycolysis

36
Q

increased fru26bp=

A

stimulates glycolysis, inhibits gluconeogenesis

37
Q

decreased fru26bp=

A

inhibits glycolysis, stimulates gluconeogenesis

38
Q

is acetylcoa an allosteric or covalent regulator of gluconeogenesis? what does it do?

A

acetyl coA triggers gluconeogenesis by activating pyruvate carboxylase, which forms oxaloacetate (first step of gluconeogenesis).

39
Q

What happesn to gluconeogenesis if AMP levels are high?

A

gluconeogenesis is halted because AMP deactivates FBP-1 and activate PFK-1, triggering GLYCOLYSIS

40
Q

how does glucagon regulate glycolysis, gluconeogenesis, and glycogen breakdown and synthesis?

A

glucgon triggers the release of cAMP, which activates PKA

PKA can turn on glycogen breakdown and turn off glycogen synthesis by phosphorylating glycogen phosphorylase B to A

PKA can turn off glycolysis and turn on gluconeogenesis through PFK-2 deactivation (decrease fru26biphosphate, thus dereasing glycolysis) and FBP-2 activation

41
Q

how does insulin regulate glycolysis, gluconeogenesis, and glycogen breakdown and synthesis?

A
  • turns on glycogen synthesis and turns off glycogen breakdown by activating glycogen synthase a, which converts UDP=glucose to glycogen)
42
Q

The final glucose (closest to the 1–>6 branch point on glycogen) is removed via ____ (hydrolysis or phospholyses)

A

hydrolysis straight into glucose.

43
Q

T/F Muscle responds to glucagon

A

false.

44
Q

What does adrenaline/ephienphrine do to glycogen breakdown? (inhibit/activate)

A

epinephrine begins glycogen breakdown because it signals to your body that it needs glucose in the blood.

  • activates glycogen breakdown via activation of adenylate cyclase cycle (makes cAMP)
45
Q

glycogen synthase is _____ activated by glucose and glucose-6-phosphate

A

allosterically activated

46
Q

what hormone inhibits glycogen synthase?

A

glucagon. Glucagon stimulates hunger, meaning they need to break down glycogen instead of making glycogen.

47
Q

Which hormone inhibits glycogen breakdown?

A

insulin. Means there is enough glucose in the blood, the body doesn’t need to go breaking down its glucose stores

48
Q

adding a glucose to glycogen chain costs how many atp? draw the mechanism for glycogen synthesis

A

costs 2 atp

49
Q

how many atp does using a glucose from glycogen save rather than a free glucose to run the glycolysis reaction?

A

saves 1 because no ATP is needed to convert glucose to glc6P. Pi phospholyses the glycogen chain to make glc1p.

50
Q

how do you get cytosolic NADH to power gluconeogenesis if glycolysis is turned off? (it will be off if gluconeogenesis is occurring)

A

breaking down lactic acid into pyruvate to make cytosolic NADH,
OR

going through the first parts of gluconeogenesis: convert pyr to oxa, and then oxa into MALATE instead. Transport malate using malate-aspartate shuttle system into the cytosol. metabolize malate into Krebs cycle to generate cytosolic NADH

51
Q

can PEP cross the mitochondrial membrane?

A

yes

52
Q

at which stage does gluconeogenesis move to the cytosol from the mitochondria?

A

after oxaloacetate is turned into pep.

53
Q

Because fructose-2, 6 biphosphate activates PFK-1, does it also activate FBP-1?

A

no, FBP is involved in gluconeogenesis rather that glycolysis and so it is inhibited if glycolysis is activated.

54
Q

How is fructose 2, 6 biphosphate itself regulated? what eenzyme is invovled with this?

A

fructose 2, 6 biphosphate comes from Fructose-6-P when it is phosphorylated by PFK-2!! (not pfk-1), the process is reversed by FBP-2

55
Q

What happens to PFK-2 when glucagon is present in the liver?

A

glucagon deactivates PFK-2, preventing fructose-6-P from being phosphoylated to fructose 2, 6 biphosphate. Because fructose 2,6,biphosphate is an ACTIVATOR of glycolysis, glycolysis is halted.

(if there is glucagon in the system, gluconeogenesis is thus turned on in order to make more glucose.

56
Q

T/F: Fatty acids can be made into glucose in the human body

A

false. only the glycoxylate cycle can turn acetyl coA’s from fatty acids into krebs intermediates that can go through glycolysis.