Glycogen Metabolism and Gluconeogenesis Flashcards

1
Q

What is the first thing that happens to glucose when it enters the cell?

A

It gets phosphorylated by hexokinase to Glucose-6-Phosphate which traps it in the cell.

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2
Q

Glycogen function in muscle vs liver

A

Glycogen in muscle is sequestered to the muscle for generation of ATP in its own cells

Liver is more generous as it uses its glycogen as a source of glucose for other tissues

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3
Q

What enzyme does the liver have that allows glucose 6 phosphate to exit the cell?

A

Glucose 6-phosphatase which cleaves the phosphate off the glucose to be able to travel via GLUT2 into the blood?

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4
Q

Why doesn’t the muscle share its glucose?

A

It doesn’t have the glucose-6-phosphatase enzyme to cleave the phosphate group which would allow it to pass through GLUT4

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5
Q

Glycogen is a polymer of _____ containing ______ and _________ linkages.

A

glucose

alpha1,4 glycosidic bonds and alpha1,6 glycosidic bonds at BRANCH points

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6
Q

Glycogen has lots of _______ linkages which allow for it to be stored at a high volume.

A

Alpha 1,6 glycosidic bonds at branch points

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7
Q

What are the 3 major pathways for glucose?

A
  1. Glycogen Synthesis
  2. Glycolysis
  3. Pentose Phosphate to made NADPH and nucleotide
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8
Q

Briefly describe the three steps of glycogen synthesis and degradation.

A
  1. G6P that has been sequestered in the cell in converted to Glucose 1- Phosphate by an isomerase.
  2. G1P is converted to UDP glucose which is the immediate glucose donor to glycogen

3.Glycogen can be broken down into G1P and glucose

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9
Q

What is UDP-glucose?

A

The product formed from G1P that serves as the immediate glucose donor

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10
Q

Glycogen is broken down into ________ and _______.

A

G1P and Glucose

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11
Q

How is G1P converted to UDP-glucose?

A
  1. The negative charged phosphate oxygen on G1P attacks the alpha phosphate of Uridine Triphosphate
  2. 2 phosphates from UTP are released combining G1P created UDP-Glucose.
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12
Q

What drives the reaction of UDP-Glucose forward?

What helps promote the incorporation of glucose into glycogen in UDP-glucose?

A

Hydrolysis of PPi from UDP-Glucose (Aka the two phosphate groups that were combined when G1P and UTP merged)

The high energy phosphoester bond formed between G1P and UTP favors incorporation of glucose into glycogen

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13
Q

________ is a primer and enzyme that catalyzes the ___________ of ______ from _______ to a _________ on the _______ on its OWN _______.

A

GlycoGENIN is a primer and enzyme that catalyzed the transfer of glucose from UDP-glucose to a hydroxyl group on the TYROSINE194 amino acid on it glycogenin.

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14
Q

Glycogenin will add ______ more _____ residues to form a ________.

What enzyme will continue this activity?

A

7 more glucosyl residues to form a primer

Glycogen Synthase

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15
Q

Synthesis of glycogen requires a _________ primer and an elongater called _______.

A

Glycogenin

Glycogen Synthase

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16
Q

What is the rate limiting step of glycogenesis?

A

Glycogen Synthase!

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17
Q

Glycogen synthase donates ______from __________ to _________ forming a _______ linkage.

Can it form the ______ bond?

A

glucose from UDP-glucose to glycogen to form an alpha 1,4 glycosidic linkage

It CANNOT form the alpha 1,6 branch point glycosidic linkages

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18
Q

Which bonds in glycogen can glycogen synthase not form?

A

Alpha 1,6

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19
Q

What can make the alpha 1,6 linkages in glycogen since ______ cannot?

A

Glycogen synthase cannot

BRANCHING ENZYME

Transfers group of glucosyl residues to the core and form the alpha 1,6 glycosidic bond with glucosyl residue in the glycogen core.

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20
Q

What is glycogenolysis and what catalyzes it?

A

Break down of glycogen catalyzed by Glycogen Phosphorylase

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21
Q

What is the rate limiting step in glycogenolysis?

A

Glycogen Phosphorylase

Uses inorganic phosphate to cleave the alpha 1,4 glycosidic bond and releases G1P.

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22
Q

Can glycogen phosphorylase break alpha 1,6 bonds?

A

NO

The DEBRANCHING enzyme uses water to cleave the alpha 1,6 glycosidic bond and released glucose.

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23
Q

Glycogen phosphorylase results in glycogen being broken down into _____ via cleavage of ________ through a _____.

Why is this important

A

G1P , Alpha 1,4 glycosidic bonds through an inorganic phosphate

The retention of phosphate on G1P makes it so that the glucose does not leave the cell automatically and the cell has time to decide what to do.

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24
Q

Glycogen Phosphorylase breaks _______ and releases _________ using ______.

Debranching enzyme breaks ________ and releases _________ using _______.

A

Alpha 1,4 - G1P using inorganic phosphate

Alpha 1,6 - Glucose using water

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25
Q

The minor product in glycogen degradation is?

A

Glucose

G1P is major.

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26
Q

Insulin favors ____________ and activates _________ in the LIVER and MUSCLE

It inhibits _________.

A

Glycogenesis , Glycogen Synthase

Glycogen Phosphorylase

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27
Q

When fasting, ________ and ________ go up and will favor __________ and activate______.

It inhibits ________.

A

Glucagon, Epinephrine

Glycogenolysis and activate Glycogen Phosphorylase

Glycogen Synthase

28
Q

What affects glycogenolysis is muscles?

A

Epinephrine - Inhibits glycogen synthase
Ca2+ and AMP and Epi- Activate glycogen phosphorylase

29
Q

Liver Glycogenolysis

A
  1. Glucagon and Epinephrine increase cAMP
  2. cAMP activate PKA which activate glycogen phosphorylase
  3. PKA inactivates glycogen synthase
  4. Increase glucose output to BLOOD
30
Q

Muscle Glycogenolysis

A

HIGH AMP activates glycogen phosphorylase due to contraction.

When muscle contracts, nerve impulse causes sarcoplasmic reticulum to release calcium to cytosol.

Calcium will bind to calmodulin to activate a phosphorylase kinase that activates glycogen phosphorylase.

If you’re running away, Epi will follow same path as cAMP/PKA path but sequesters glucose to the muscle cell.

31
Q

What is GlucoNEOgenesis ?

A

New glucose being made from NON-carbohydrate precursors

32
Q

What is the function of gluconeogenesis and where does it primarily occur?

A

Increase blood sugar

LIVER

33
Q

Insulin stimulates ________.

A

Glycolysis
Glycogenesis (when cells have enough ATP)
Synthesis of fats and proteins

34
Q

What is the only hormone that reduces blood glucose?

A

Insulin

35
Q

Glucagon and stress hormones increases _________.

A

hepatic glucose output
mobilize fuels from adipose (fatty acids ) and proteins (amino acids)

Glycogenolysis
Gluconeogenesis
Lipolysis

36
Q

What are the 4 sources of material needed for gluconeogenesis?

A
  1. Liver glycogenolysis and gluconeogenesis release glucose to blood
  2. Fatty acids from adipose are used as fuel in liver and muscle via beta-oxidation
  3. Amino Acids from muscle provide CARBON skeleton for liver gluconeogenesis
  4. Glycerol from triglycerides provide CARBON skeleton for liver gluconeogenesis?
37
Q

What provides the carbon skeleton for gluconeogenesis?

A

Muscle Amino Acids

Glycerol from Triglycerides

38
Q

The most important source of carbon for glucose are _________.

A

Amino Acids

39
Q

________ forms a gluconeogenic precursor (DHAP).

A

Glycerol

Glycerol is released from triglycerides.

39
Q

What amino acids can be converted to pyruvate?

A

Lactate and Alanine

40
Q

Carbons in the fatty acids cannot be used directly as a gluconeogenic precursor because ________.

A

Oxidation of fatty acids yield Acetyl CoA which cannot be converted back to pyruvate and also cannot enter the TCA cycle because it looses two carbons.

40
Q

Glycolysis is the breakdown of glucose into energy forms. Gluconeogenesis is _______________ and happens to be very similar to the reverse process of glycolysis with differences at ________________.

A

creation of glucose from precursors and happens to be very similar to the reverse process of glycolysis excepet at 3 HIGH EXERGONIC STEPS

41
Q

What are the three steps that differ between glycolysis and the reverse gluconeogenesis pathway?

A

Glycolysis

  1. Hexokinase - G6P
  2. PFK-1 - F1,6,BP
  3. Pyruvate Kinase - PEP to Pyruvate

Gluconeogenesis

  1. Pyruvate to PEP - Pyruvate Carboxylase and PEPCK
  2. F1,6BP to F6P - F 1,6 BPase
  3. G6P - G6Pase
42
Q

Reciprocal regulation in Liver

A

Gluconeogenesis and Glycolysis have an inverse regulatory interaction

43
Q

Steps of Gluconeogenesis

First is the conversion of ________ to __________ in the ________.

This requires _________.

A

Pyruvate to PEP in the mitochondrial matrix

This requires Pyruvate Carboxylase, PEPCK and 2 ATP

Pyruvate carboxylase adds a bicarbonate to pyruvate to make it oxaloacetate. PEPCK converts oxaloacetate to PEP.

44
Q

Gluconeogenesis occurs in the _________.

A

Mitochondrial matric

45
Q

In humans, we have two types of PEPCK. What are they?

Which one do we care about?

A

Cytosolic and Mitochodrial

Cytosolic PEPCK

46
Q

Cytosolic PEPCK is controlled by _________ and __________.

A

Glucagon and Epinephrine

47
Q

Step 2 of Gluconeogenesis

PEP has been made and goes through a series of reactions to become _____________. This molecule is dephosphorylated by _______ to ______.

A

F1,6 Bisphosphate by FBPase-1 to F,6,Phosphate

48
Q

Describe the difference in usage between PFK-1 and FBPase-1

A

Aside from have opposite functions (kinase vs phosphatase)

PFK-1 uses a phosphate from ATP

FBPase-1 hydrolyzes the phosphoester bond in F1,6BP

49
Q

F26BP activates __________ but inactivates ____________.

A

PFK-1 - Activates

FBPase-1 - Inactivates

50
Q

Where does F26BP come from?

A

PFK2 converts F6P into F26BP.

51
Q

PFK-2 is a bifunctional enzyme. Describe this statement.

A

PFK-2 converts F6P to F26BP

it can also act as an FBPase-2 and convert F26BP back to F6P.

52
Q

Insulin stimulates PFK2 to _________ while glucagon and epinephrine ________.

A

produce F26BP, stimulate its breakdown

53
Q

PFK-2 and FBPase-2 are the same enzyme.

True or False

A

Technically yes!

54
Q

Step 3 of gluconeogensis.

You know this one! LAST STEP!

A

G6Phosphatase only found in the liver uses the phosphoester bond to catalyze the removal of the phosphate group so glucose can leave the leaver

55
Q

F26BP activates ______ and inhibits _______.

A

PFK1 and inhibits F16BPase

56
Q

cAMP/PKA in the _____ will inhibit _____.

A

liver, Pyruvate kinase

57
Q

Acetyl CoA activates ________.

A

Pyruvate carboxylase to turn pyruvate into oxaloacetate

58
Q

Insulin ______ glucokinase in the cell.

A

increases expression of (hexokinase for body)

59
Q

Epinephrine, Glucagon and Cortisol increase expression of _________.

A

G6P Phosphatase
F16BPase
PEPCK

This means blood sugar is LOW!

60
Q

Fed means ______ glucose for energy.

Hungry means _________ glucose for energy.

A

use

don’t use; save it

61
Q

There are only 2 cells that have glucagon receptors. What are they?

A

Liver and Adipose

Makes sense because these are the ones that store glucose

62
Q

If glycolysis is high, _______ is also high

A

Fatty acid SYNTHESIS and TG SYNTHESIS

63
Q

In starvation ______ decreases as a protective mechanism.

A

Amino Acid Degradation and thus decreased Urinary Nitrogen

64
Q

Change in Blood Fuels during Fasting

A
  1. Fasting <24

Urea high due to high gluconeogenesis (break down of AA)

Free FA increase due to lipolysis

  1. Starvation >3 days

Ketone bodies

AA degradation and thus urea production decrease as a protective mechansim