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Biochem 1 > Gluconeogenesis > Flashcards

Gluconeogenesis Flashcards

1
Q

What is gluconeogenesis

A

The formation of glucose from non-carbohydrate substrates.

Important source of glucose during fasting and exercise

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2
Q

What is the only tissue that release glucose in the blood in significantly quantitative amounts

A

Liver

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3
Q

Except for the irreversible steps, gluconeogenesis is the reverse of ________

A

glycolysis

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4
Q

Where does gluconeogenesis occur?

A

cytoplasm, mitochondria`

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5
Q

Describe blood glucose in the fed, fasting, starved states

A
  • Immediately after meal, there is glucose in the blood from the food we ate - major source of blood glucose
  • w/i ~2 hours, glucose that is oxidized comes mainly from the liver through glycogenolysis (breaking glycogen down into glucose)
  • After ~12 hours, gluconeogenesis is the major source of blood glucose
  • After ~24 hours, this is long term fasting. Glucose oxidation in muscle is suppressed and there is increased fatty acid which can be used by muscle
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6
Q

Contribution of gluconeogenesis to blood glucose ________ with fasting and/or exercise duration

A

increases

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7
Q

What regulates altered glucose production and metabolism

A

Hormones

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8
Q

After a meal, insulin is ____ which promotes _____ of fuels that are being and the _____ of fuels that are not being used

A

increased
utilization (glycolysis)
Storage (stores fats as triglycerides, glucose as glycogen and incorporation of amino acids into proteins)

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9
Q

When fuel depletes, glucagon and stress hormones _____ hepatic glucose output from the liver and ______ fuels from adipose (fatty acids) and muscles (amino acids)

A

increase

mobilize

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10
Q

_____ and _____ are precursors for pyruvate (which can enter gluconeogenesis)

A

lactate

alanine (if you take the amino group off, you get pyruvate)

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11
Q

______ amino acids are AA that be converted to glucose

A

glucogenic

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12
Q

_______ from the muscles are quantitatively the most important source of glucose precursors for gluconeogenesis

A

Glucogenic AA

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13
Q

When we are not eating, our major source of gluconeogenic precursors are

A

AA
The main reason for eating proteins is to replace the AA you lost during fasting.

longer b/w your meals, more proteins you need to eat

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14
Q

Which gluconeogenic precursor is released from lipolysis of triglycerides

A

Glycerol

Fatty acid portion of triglycerides is not a glucogenic precursor. The H atoms in the alkyl chain provide H for the ETC. Most energy come from fatty acid portion
Oxidation of fatty acids yields Acetyl CoA

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15
Q

What are the gluconeogenic precursors

A

Lactate and alanine
Glucogenic AA
Glycerol

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16
Q

______ is the carbon skeleton product of fatty acid oxidation

A

Acetyl CoA

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17
Q

Acetyl CoA can be converted into glucose, true or false

A

false. It cannot

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18
Q

Can fat be converted into glucose?

Explain

A

No. BC acetyl CoA cannot be converted into glucose

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19
Q

Are the gluconeogenic steps the reverse of those in glycolysis?

A

Most are, but not all. The differences are at 3 highly exergonic rate limiting steps

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20
Q

What are the different steps in glycolysis and gluconeogenesis?

A
  • Phosphorylation of glucose to glucose-6-P by hexokinase
  • Conversion of F-6-P to frutose-1,6-bisphosphate by PFK1
  • second level phosphorylation step by pyruvate kinase
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21
Q

What does the differences in the 3 steps (b/w glycolysis and gluconeogenesis) allows?

A

allows favorable reactions in the reverse direction

Allows reciprocal control of these steps tp avoid futile cycle (ie reciprocally control the two different pathways - when one is favored, we can slow down the other)

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22
Q

What are the enzymes unique to glycolysis

A

Step 1: Glucose + ATP to glucose-6-P + ADP by hexokinase glucokinase (liver, pancreas)

Step 2: F-6-P +ATP tp F-1,6-BP + ADP by PKF-1

Step 3: PEP to pyruvate by pyruvate kinase

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23
Q

What are the enzymes unique to gluconeogenesis?

A

Step 1: pyruvate to PEP
by pyruvate carboxylase and PEPCK

Step 2: fructose-1,6-BP to fructose-6-phosphate by F-1,6-BPase

Step 3: glucose-6-phosphate to glucose by Glucose-6-phosphatase (liver only because this is where the pathway would occur)
Liver and kidney are the only tissues that express this enzyme

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24
Q

Why does glucose need to be dephosphorylated

A

Bc transporters cannot bind to it while phosphorylated ie it can’t leave the cell

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25
Q

Gluconeogenesis Step #1: explain the conversion of pyruvate to PEP

A

requires 2 steps
- In the mitochondrial matrix, pyruvate carboxylate condenses CO2 to pyruvate to form oxaloacetate . This requires ATP

  • PEPCK decarboxylates oxaloacetate to phosphoenolpyruvate. Requires GTP
  • there is PEPCK in the cytosol and in the mitochondria however the one is the cytosol is regulated by hormones so that’s the one we will talk about
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26
Q

Gluconeogenesis Step #1b: PEPCK converts oxaloacetate to PEP via malate shuttle

A

In the mitochondrial matrix, oxaloacetate can’t leave the cell so it is reduced to malate

Malate can leave the mitochondria through malate-aspartate shuttle

oxaloacetate from mitochondria is transported to cytosol by malate-aspartate shuttle

once it is in the cytosol, malate is converted back to oxaloacetate which is converted to PEP by PEPCK

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27
Q

Why does gluconeogenesis occur in the cytosol in mitochondria?

A

Because of the first step, to convert pyruvate to oxaloacetate occurs in the mitochondria (the enzyme is in the mitochondria)

28
Q

Gluconeogenesis Step #2: F16BP to F6P by Fuctose-1,6-bisphosphatase (FBPase1)

A

PBPase-1 hydrolyzes phosphate at the 1 position. enough energy to go opposite direction from glycolysis

29
Q

Gluconeogenesis Step #3: Glucose-6-phosphatase converts glucose-6-phosphate to glucose

A

Not enough energy to add phosphate to ADP like in glycolysis, very endergonic reaction

Instead, we hydrolyze ester bond in glucose-6-phosphate which has high energy with glucose -6-phosphatase
liver is only tissue which expresses it

30
Q

How do we go from pyruvate to glucose?

A

with 6ATP equivalents and 2 NADH

31
Q

Does increased or decreased cytosolic NADH favor gluconeogenesis?

32
Q

What is the tissue that carries out all the steps of gluconeogenesis?

33
Q

Under what conditions does gluconeogenesis occurs?

A

fasting conditions and exercise

34
Q

Draw the 3 different steps of glycolysis and gluconeogenesis in the liver

A

white board

slide 17

35
Q

A common intermediate in the conversion of glycerol and lactate to glucose is which of the following?

A. Pyruvate
B. Oxaloacetate
C. Malate
D. Glucose-6-phosphate
E. Phosphoenolpyruvate
A

D. Glucose-6-phosphate

Glycerol gets added into the pathway a bit later than lactate

36
Q

What are factors regulating glycolysis and gluconeogenesis in the liver?

A

Cellular metabolites eg:
- fructose-2,6-bisphosphate
- Energy status of the cell AMP, ADP/ATP (ratio)
NADH/NAD+ (ratio)

Hormonal regulation:

  • insulin - favors glycolysis bc it promotes fuel utilization
  • glucagon, cortisol, epinephrine - favor gluconeogenesis in the liver
37
Q

Insulin favors glycolysis or gluconeogenesis?

A

Glycolysis

38
Q

Glucagon, cortisol, epinephrine favor glycolysis or gluconeogenesis?

A

Gluconeogenesis in the liver

39
Q

Does high or low AMP favor gluconeogenesis? Why?

A

low

Low AMP means energy status of the cell is high. We have ATP and want to use it

40
Q

A low ratio of ADP/ATP favors

A

Gluconeogenesis

low ADP means ATP is high. We have ATP and want to use it,

41
Q

A high ratio of NADH/NAD+ favors

A

gluconeogenesis

42
Q

Gluconeogenesis is favored by high or low insulin/glucagon ratio?

A

Low ratio of insulin/glucagon.

This means glucagon is high

43
Q

What is the source of energy for gluconeogenesis

A

Fatty acids from the lipids

44
Q

Fructose-2,6-bisphosphate in the liver mirrors which hormone

A

blood glucose

When glucose is high, F26BP is high

45
Q

Which enzyme interconverts F6P and F26BP?

A

PFK2 (bifunctional enzyme with 2 enzyme activities/active sites)

46
Q

What are the activities of PFK-2?

A
  1. PFK2 activity - adds a phosphate from ATP to F6P to generate F26BP
  2. Activity catalyzed to remove the phosphate from F26BP to make F6P
47
Q

How is PFK-2 activity regulated in the liver

A

by insulin, glucagon and epinephrine

48
Q

In the committed step of glycolysis of PFK1, what is the role of F26BP

A

a potent allosteric activator of PFK1

w/o F26BP, PFK1 doesn’t have enough activity to carry out glycolysis

49
Q

What is the relationship between F26BP and FBPase-1 (gluconeogenesis)

A

F26BP potently inhibits FBPase-1

50
Q

Does F26BP favor glycolysis or gluconeogenesis?

A

glycolysis

51
Q

Insulin _____ F26BP by increasing the activity of ____

A

increases

PFK2

52
Q

Glucagon and epinephrine ____ F26BP by increasing the activity of ______ and decreasing the activity of ____

A

decreases
FBPase2 (removes phosphate from F26BP)
PFK2

53
Q

How will increased glucagon affect F26BP levels?
How will this influence glycolysis?
Gluconeogenesis?

A

decrease it
Decrease it
Increase it

54
Q

What are the effects of glucocorticoids?

A
  • Are steroid hormones and don’t have immediate effect
  • Increase expression of gluconeogenesis and raises blood glucose
  • Mobilizes release of AA from proteins from extrahepatic tissues
  • decrease uptake of glucose in muscle and adipose (preserve glucose for other tissues that need it)
  • increase lipolysis of triglycerides in adipose tissue release fatty acids
55
Q

PEPCK is turned ____ by glucagon and cortisol and ___ by insulin

56
Q

cAMP _____ expression of PEPCK

57
Q

When glucagon and epinephrine bind to receptor on the cell surface of liver, they ______ expression of PEPCK

58
Q

How to reciprocally control glycolysis and gluconeogenesis in the liver?

A
  1. Altering the enzyme activity through phosphorylation and allosteric modifiers
    eg of modifies -
    F26BP activates PFK1; inhibits F16BPase
    cAMP inhibits pyruvate kinase in the liver
    Acetyl CoA activates pyruvate carboxylase
  2. Altering the level of enzyme expression eg
    - insulin increases
    the expression of glucokinase
    - epinephrine, glucagon and cortisol increase expression of glucose-6-phosphatase, F16BP, PEPCK
59
Q

Glycolysis is favoured in the fed state with elevated:

A

blood glucose
blood insulin
liver F26BP
AMP (means energy status is low and this favors glycolysis)

60
Q

Gluconeogenesis is favoured in fasting state with decreased:

A

blood glucose
blood insulin
liver F26BP
AMP (meaning you need to have ATP)

61
Q

What happens if F-6-P is acted on by PFK-1? Reversible or irreversible?

What happens if F-6-P is acted on by PFK-2?
Reversible or irreversible

A

We get F-1,6-BP
Irreversible

We get F-2,6-BP
Reversible with FBPase-2, catalyzed by PFK-2

62
Q

cAMP inactivates pyruvate kinase and therefore inactivates ______

A

glycolysis

63
Q

F-2,6-BF inhibits F-1,6-BPase and therefore inactivates _____

A

gluconeogenesis

64
Q

F-2,6-BF activates PKF1 and therefore activates _____

A

glycolysis

65
Q

acetyl CoA activates pyruvate carboxylate and therefore activates ______

A

gluconeogenesis

66
Q

insulin ______ expression of glucokinase

67
Q

epinephrine, glucagon and cortisol _____ expression of glucose 6-phosphatse, F-1,6-BPase and phosphoenolpyruvate carboxylase

Biochem 1 (22 decks)

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