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Week 8- SHANE > Gluconeogenesis > Flashcards

Gluconeogenesis Flashcards

1
Q

T or F. Gluconeogenesis is the pathway for synthesizing glucose from carbohydrate precursors

A

F. It is the pathway from non-carbohydrate precursors

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2
Q

What kinds of the non-carbohydrate precursors are the basis of gluconeogenesis?

A

lactate, pyruvate, glycerol, amino acids

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3
Q

Where does gluconeogenesis primarily occur?

A

liver

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4
Q

2-3 hrs after a meal, where is BG coming from?

A

glycogenolysis

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5
Q

16-24 hrs after a meal, where is BG coming from?

A

gluconeogenesis

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6
Q

What is the secondary site of gluconeogenesis?

A

kidney

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7
Q

What are the three main carbon sources for gluconeogenesis?

A

lactate, amino acids (alanine), and glycerol

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8
Q

Where does the glycerol for gluconeogenesis come from?

A

adipose lipolysis

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9
Q

Where do the amino acids (alanine) for gluconeogenesis come from?

A

glycolysis and amino acid metabolism

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10
Q

Where does the lactate for gluconeogenesis come from?

A

muscle and RBC glycolysis

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11
Q

What are the irreversible enzymes of glycolysis?

A

glucokinase, PFK-1, pyruvate kinase, pyruvate dehydrogenase

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12
Q

What does pyruvate dehydrogenase do?

A

converts pyruvate into acetyl CoA in glycolysis

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13
Q

T or F. Gluconeogenesis occurs under conditions where glucokinase, PFK-1, and pyruvate kinase are under low activity

A

T. This minimizes glycolysis

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14
Q

What is the first step of gluconeogenesis?

A

pyruvate is concerted to oxaloacetate

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15
Q

What enzyme is involved with conversion of pyruvate to oxaloacetate?

A

pyruvate carboxylase (using ATP)

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16
Q

Where does the conversion of pyruvate to oxaloacetate occur?

A

inside the mitochondria

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17
Q

What must oxaloacetate be converted to before leaving the mitochondria and why?

A

either malate or aspirate (using NADH and making NAD+) because oxaloacetate in not diffusible across the membrane

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18
Q

What happens to malate and aspartate after leaving the mitochondria?

A

they are reconverted to oxaloacetate

NOTE: malate does this using NAD+ and making NADH as a bi-product

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19
Q

What happens to oxaloacetate in the cytosol?

A

it is converted to PEP by phosphenol-pyruvate carboxykinase (PEPCK) by using GTP (and giving off GDP and CO2 as bi-products)

20
Q

What is pyruvate carboxylase activated by?

A

Acetyl CoA (coming from FA oxidation)

21
Q

What does pyruvate carboxylase require to work?

A

biotin and CO2

22
Q

What else does pyruvate carboxylase do cells?

A

responsible for maintaining OAA concentrations for the TCA cycle

23
Q

Is pyruvate carboxylase active in both fed and fasting cycles? Why?

A

Yes. because it is responsible for maintaining OAA concentrations for the TCA cycle during fed state and responsible for the conversion of pyruvate to oxaloacetate during fasting stages

24
Q

Is pyruvate carboxykinase found in the cytosol or the mitochondria or both?

A

mitochondria only

25
Q

Is phosphenol-pyruvate carboxykinase (PEPCK) found in the cytosol or the mitochondria or both?

A

both

26
Q

Can oxaloacetate be converted to PEP both in the mitochondria and in the cytosol? How?

A

Yes.

In the mitochondria, if there are mitochondria PEPCKs present, they will convert OAA directly to PEP (without intermediates). PEP is diffusable and can cross the mitochondrial membrane to the cytosol

Another way is to convert OAA to malate and aspartate to move out of the mitochondria, reconvert to OAA, and be converted to PEP by PEPCK

27
Q

How is PEP converted to glyceraldehyde-3-p?

A

reversible of the steps of glycolysis (conversion would require 2 ATPs and a GTP)- know where from

28
Q

What would be the steps needed to use glycerol as a pre-cursor of gluconeogenesis?

A

1) glycerol kinase would convert glycerol to glycerol-3-p using glycerol kinase (using hydrolysis of ATP)
2) glycerol-3-p would be converted to DHAP using NAD+ (and giving off NADH as a bi-product)

29
Q

Why would using glycerol as a pre-cursor for gluconeogenesis be energy saving vs using pyruvate?

A

it only uses 1 ATP vs pyruvate conversion using 2 ATPs and a GTP

30
Q

Do glucose-6-phosphatase and fructose-1,6-bisphosphatase step-for-step reverse the actions of glucokinase and PFK-1?

A

No. glucokinase and PFK-1 use hydrolysis of ATP while glucose-6-phosphatase and fructose-1,6-bisphosphatase do not give off ATP and release a free glucose and an inorganic phosphate group, respectively

31
Q

When does gluconeogenesis occur?

A

fasting, prolonged exercise, stress, high protein diet

32
Q

What factors promote gluconeogenesis?

A

availability of substrates (glycerol, AAs, lactate)

33
Q

What steps of gluconeogenesis are regulated?

A

pyruvate -> PEP
fructose-1,6-bisphosphatase -> F-6-P
G-6-phosphatase -> glucose

34
Q

How is pyruvate dehydrogenase regulated?

A

1) during fasting, adipose TAG is broken down and FA are released and sent to the liver where they undergo B-oxidation to Acetyl CoA, NADH, and ATP.
2) As a consequence, ADP levels decrease and pyruvate dehydrogenase is phosphorylated to its inactive form
3) Thus, acetyl CoA is not formed from pyruvate

35
Q

What activates pyruvate carboxylase?

A

acetyl CoA produced from the oxidation of FA

36
Q

How does acetyl CoA regulate gluconeogeneis?

A

1) activates pyruvate carboxylase

2) inhibits pyruvate dehydrogenase

37
Q

How is PEPCK upregulated?

A

glucagon activates adenylyl cyclase which makes cAMP (from ATP), which then activates PKA.

PKA stimulates the transcription of the PEPCK gene

38
Q

What activates adenylyl cyclase during fasting?

A

glucagon

39
Q

What activates adenylyl cyclase during exercise?

A

epinephrine

40
Q

How is pyruvate kinase regulated?

A

PKA induced from glucagon inactivates it

41
Q

What regulates the activity of fructose-1,6-bisphosphatase?

A

fructose-2,6-bisphosphate levels (high levels will reduce the activity of fructose-1,6-bisphosphatase and will increase the activity of PFK-1)

42
Q

What enzyme is responsible for the production of fructose-2,6-bisphosphate?

A

PFK-2

43
Q

What does the kinase domain of PFK-2 do and what up regulates it? When is it active

A

F6-p converted to f-2,6-bisphosphate

high f6-p levels

active when PFK-2 is de-phosphorylated

44
Q

What does the phosphatase domain of PFK-2 do and what up regulates it?

A

converts f-2,6-bisphosphate to f6-p

cAMP activated PKA activates it by phosphorylating it (aka when PFK-2 is phosphylated, its undergoing gluconeogenesis)

active when PFK-2 is phosphorylated

45
Q

How many ATPs and GTPs are need to make glucose from glycerol?

A

2 ATPs, no GTP

46
Q

How many ATPs and GTPs are need to make glucose from pyruvate?

A

4 ATPs, 2 GTPs

47
Q

Where does the energy (aka ATPs and GTPs) needed for gluconeogenesis come from?

A

oxidation of fatty acids and lactate

Week 8- SHANE (23 decks)

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