Gluconeogenesis Flashcards

1
Q

What precursors can be used for gluconeogenesis?

A

Lactate, pyruvate, glycerol, amino acids, etc.

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2
Q

Where does gluconeogenesis occur?

A

Primarily in liver

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3
Q

Why is gluconeogenesis essential?

A

Because brain and RBC’s require glucose and cannot synthesize it on their own

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4
Q

After a meal what is the source of blood glucose?

A

Digested food

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5
Q

After 2-3 hours fasting what is source of glucose?

A

Glycogenolysis

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6
Q

After prolonged fasting what is the source of glucose?

A

Gluconeogenesis

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7
Q

(393) During exercise what is the source of glucose?

A

(393) Glycogenolysis and gluconeogenesis

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8
Q

(395) What glycolytic enzymes does gluconeogenesis bypass

A

Glucokinase, PFK1, pyruvate kinase

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9
Q

What enzymes are used to bypass the glycolytic reactions?

A

Pyruvate carboxylase, PEPCK, F-1,6-bipshosphatase, G6Pase

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10
Q

What does pyruvate to oxaloacetate reaction require?

A

Pyruvate carboxylase, Biotin, active in both fed and fasting state

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11
Q

What activates pyruvate carboxylase?

A

Acetyl Coa (means TCA is backed up and we should synthesize glucose)

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12
Q

(399) What does PEPCK require to convert oxaloacetate into PEP?

A

GTP

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13
Q

The steps between PEP and G3P occurs where? And what is the reaction pathways for these steps?

A

Cytosol, reverse of glycolysis

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14
Q

What are three ways gluconeogenesis is regulated?

A

Amount of substrate, amount of enzyme, activity of enzyme

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15
Q

What activates pyruvate carboxylase?

A

Acetyl CoA

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16
Q

(403) What inhibits PDH?

A

Acetyl CoA

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17
Q

Describe regulation of the amount of pepck?

A

Glucagon /epinephrine signal adenylate cyclasecAMPPKAtranscription factors more PEPCK

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18
Q

What inhibits pyruvate kinase?

A

cAMP and PKA (opposite to PEPCK since this is a glycolytic vs. gluconeogenitic enzyme)

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19
Q

What activates F16Bpase?

A

low F-2,6 BP

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20
Q

(407) What is the energetic requirement for gluconeogenesis?

A

4 ATP, 2 GTP, and 2 NADH

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21
Q

(394) What cellular locations does gluconeogenesis occur?

A

Pyruvate carboxylase in mitochondria, PEPCK in between mitochondria and cytosol, rest is in cytosol except for G6Pase which is in ER

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22
Q

Glycolysis is to Glucokinase as gluconeogenesis is to ___________?

A

Glucose -6- Phosphatase

23
Q

Glycolysis is to Phosphofructokinase as Gluconeogenesis is to _____________?

A

Fructose Bis-Phosphatase

24
Q

Glysolysis is to Pyruvate kinase as gluconeogenesis is to ____________?

A

PEP Carboxykinase

25
Q

Glysolysis is to Pyruvate dehydrogenase as gluconeogenesis is to ___________?

A

Pyruvate carboxylase

26
Q

What is the pathway for synthesizing glucose from lactate, pyruvate, glycerol, amino acids?

A

gluconeogenesis

27
Q

What is the only source of of glucose in the fasting state?

A

gluconeogenesis

28
Q

Why is gluconeogenesis essential in the brain and RBCs?

A

They require glucose and cannot synthesize glucose on their own because fatty acids cannot cross blood brain barrier

29
Q

Why can gluconeogenesis occur only in the liver and long starvation occur in the kidney?

A

only tissues that express G-6-Pase

30
Q

After 2-3 hours of fasting, what allows for glucose?

A

glycogen is degraded to glucose via glycogenolysis

31
Q

During exercise, glucose is supplied to the blood by what?

A

gluconeogenesis and glycogenesis

32
Q

What is the relationship of glycogenolysis and gluconeogenesis after a meal?

A

glycogenolysis occurs quickly and gluconeogenesis occurs more gradually

33
Q

What pathway is used to recycle carbons during glycolysis and in the Cori and Alanine cycles?

A

gluconeogenesis

34
Q

What is the end product of RBC in glycolysis?

A

lactate

35
Q

What are the 3 major carbon sources for gluconeogenesis?

A

lactate (pyruvate), amino acids (alanine), glycerol (adipocyte lipolysis)

36
Q

What irreversible enzymes of glycolysis must be bypassed in order for gluconeogenesis to occur?

A

GK, PFK-1, pyruvate kinase

37
Q

What are the 4 irreversible enzymes that bypass the same as glycolysis?

A

pyruvate carboxylase, PEPCK, FBPase-1, G6Pase

38
Q

In relation to GK, PFK-1, and pyruvate kinase, when does gluconeogenesis occur? What is the result?

A
  • low activity of each of the molecules

- minimizes glycolysis and low pyruvate dehydrogenase activity while saving pyruvate for gluconeogenesis

39
Q

What are the key reactions or regulatory steps of gluconeogenesis?

A
  1. pyruvate to PEP
  2. F-1,6-bisphosphate to Fru-6-phosphate
  3. G-6-P to glucose
40
Q

Describe the conversion to pyruvate to PEP via specific enzymes involved which occurs in the liver

A
  1. Pyruvate => OAA via PC (ATP requiring)
  2. OAA uses the malate/aspartate shuttle to cross inner Mt membrane
  3. OAA => decarboxylated by PEPCK (GTP requiring)
  4. Phosphoenolpyruvate => fru-1,6-bispho
41
Q

Describe the conversion of Fru-1,6-biphos to Fru-6-phos

A
  1. Fructose 1,6 biphos => fru-6 phos via 1,6-biphosphatase

2. Fru-6-P converted to G-6-P

42
Q

Describe conversion from G-6-P to glucose

A
  1. G-6-P produces FREE GLUCOSE via G-6-Pase

2. G-6-Pase involved in both gluconeogenesis and glycogenolysis

43
Q

T/F Conversion from pyruvate to PEP occurs in the cytosol only

A

False, PC enzyme is located in the Mt so must occur there but PEPCK can be located in the Mt and cytosol

44
Q

Where are the fatty acids oxidized and where are they released from? What molecules are they oxidized to?

A

Released from adipose tissue that travel to the liver where they under go Beta oxidation to acetyl CoA, NADH, ATP

45
Q

What are the effects of Acetyl CoA in the first step of gluconeogenesis?

A
  1. activates PC

2. inhibits pyruvate dehydrogenase

46
Q

Why must pyruvate dehydrogenase be inhibited?

A

Pyruvate would be used in the TCA cycle thus disrupting the generation of PEP

47
Q

Describe the relationship of Fru-1,6-Bisphos, PFK-1

A

When F-2,6-P is low, PFK-1 is less active and F-1,6-biphos is more active

48
Q

Describe the domains of PFK-2

A

kinase domain: F6-P => F-2,6-P

phosphatase domain: F-2,6-BP hydrolyzed to F-6-P

49
Q

How is pyruvate kinase inactivated?

A

Glucagon via cAMP and PKA causes pyruvate kinase to be phosphorylated

50
Q

The synthesis of F-2,6-P is controlled by what? Describe the relationships

A

insulin and glucagon
Increase glucagon and increase cAMP then PKA is activated => gluconeogenesis promoted

increase insulin => decrease cAMP => dephosphorylation of PFK2 => glycolysis promotion

51
Q

T/F GK is inactive during gluconeogenesis, explain

A

True, high Km for glucose so since glucose concentrations are low then the GK is not needed

52
Q

What supplies energy for gluconeogenesis?

A

Fatty acid oxidation

Oxidation of lactate

53
Q

Describe the relationship of insulin in the liver, muscle, adipose

A

liver: insulin promotes storage of glucose as glycogen and prod. of TAG

Muscle: insulin stimulates transport of glucose into cell and glycogen synthesis

Adipose: insulin stimulates transport of glucose into adipose and TAG production

54
Q

What is involved in the blood glucose levels in the fasting state?

A

change in insulin and glucagon levels, stimulation of glycogenolysis and gluconeogenesis