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Biochem > Gluconeogenesis > Flashcards

Gluconeogenesis Flashcards

1
Q

When does glycogenolysis happen? When does gluconeogenesis happen?

A

When blood glucose starts running lower, the liver performs glycogenolysis mostly.

When glycogen storage starts running low (e.g. sleep), then glycogenolysis falls and gluconeogenesis rises.

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2
Q

Gluconeogenesis

A

Formation of glucose from non-carbohydrate precursors

Reverses glycolysis

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3
Q

____ is performed in the cytosol of every cell of our body.

___ mainly occurs in hepatocytes, but also kidney and intestinal epithelium.

A

Glycolysis in every cell

Gluconeogenesis in liver, kidney, and intestine

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4
Q

How does gluconeogenesis reverse the pyruvate kinase rxn? Where?

A
  1. Pyruvate –<strong><em>pyruvate carboxylase, ATP, biotin</em></strong>–> oxaloacetic acid
    1. ​Ligase rxn
  2. Oxaloacetic acid –<strong>PEP carboxykinase (PEPCK), GTP, CO2</strong> –> PEP

both occur int he mitochondria + cytosol

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5
Q

How to reverse the PFK-1 rxn? Where?

A

F16BP –FBPase-1 +Pi<strong><em> </em></strong>–> F6P

Cytosol

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6
Q

How to reverse the hexokinase reaction? Where?

A

Glucose-6-phosphate –glucose-6-phosphatase + Pi–> Glucose

Occurs in the ER

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7
Q

Muscle cells perform ___, but it doesn’t affect BLOOD glucose because it’s used internally.

Muscle cells CANNOT perform ___

A

Can perform glycogenlysis

CANNOT perform gluconeogenesis

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8
Q

Which two gluconeogenesis-specific enzymes do adipose cells have that allow them to perofrm glyceroneogenesis??

A

Pyruvate carboxylaes

PEPCK

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9
Q

Reaction of gluconeogenesis

A

2 pyruvate + 4ATP + 2GTP + 2NADH + 2H+ + 2H2O

–>

Glucose + 4ADP + 2GDP + 6Pi + 2NAD+

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10
Q

2 ATP were consumed in the pyruvate carboxylase rxn and 2 GTP were consumed in the following PEPCk reaction.

What about the other 2 ATP used in gluconeogenesis?

What about the 2 NADH that got used?

A

2ATP comes from reversing the phosphoglycerate kinase reaction (which generated 2 ATP in glycolysis)

2NADH comes from reversing the the glyceraldehyde 3-phosphate dehydrogenase reaction (generated 2NADH in glycolysis)

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11
Q

Gluconeogenic precursors:

Ala (most common)

Glycerol

Other aa (e.g. Asp)

Lactic acid

A
  • Ala -> pyruvate
  • Glycerol -> DHAP
  • Other aa (e.g. Asp) -> oxaloacetate
    • (Bypasses ATP hydrolyis of pyruvate carboxylase)
  • Lactic acid -> pyruvate
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12
Q

How to hormones mediate changes to enzymes?

A

Protein covalent modifications

Allosteric control mechanisms

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13
Q

Glucose-6-phosphatase and hexokinase are both active in hepatic cells. How do liver cells regulate their opposing pahtways?

A

Glucokinase is in the cytosol

Glucose-6-phosphatase is in the ER

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14
Q

When glucose is low, where is glucokinase? where is glucose 6phosphatase?

A

Glucokinase is sequestered to the nucleus

Glucose 6-phosphtase is active in the ER lumen

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15
Q

When [glucose 6 phosphate] rises in the cell

A

It’s transported into the ER by a glucose 6-phosphate transporter to be hydrolyzed by the phosphatase to produce glucose.

Transported back to the cytosol, then out to the blood if blood glucose is lower than cytosol

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16
Q

Both PFK-1 (glycolysis) and FBPase-1 (gluconeogenesis) are regulated how?

A

Allosteric regulation by Fructose 2,6-bisphosphate, which

Stimulates PFK-1

Inhibits FBPase-1

17
Q

___ catalyzes the production of F2,6BP from fructose-6-phosphate

A

PFK-2

18
Q

__ catalyzes the hydrolyzes the cabron-2 phosphate from F2,6BP to regenerate Fructose 6-phosphate

A

FBPase-2

19
Q

The bifuncitonal enzyme is

A

PFK-2 & FBPase2

Hormonal signals in response to blood glucose determine which of the opposing enzymatic activities is stimualted or repressed.

20
Q

If blood glucose is high, what happens to the bifunctional enzyme?

What if blood glucose is low?

A

Dephosphorylation -> increases PFK-2 and decreases FBPase-2 -> glycolysis

Phosphorylation -> decreases PFK-2 and increases FBPase-2 –> gluconeogenesis

21
Q

Effect of glucagon

A
  • Phosphorylate the bifunctional enzyme to inhibit PFK-2 and activate FBPase-2.
  • Phosphorylation & inactivation of pyruvate kinase
    • –> Accumulates PEP to use directly in gluconeogenesis (saves ATP)
  • Stimulate transcription of Glucose-6-phosphatase, FBPase-1, PEPCK
  • Inhibit transcription of glucokinase, PFK-1, and pyruvate kinase
22
Q

3 ways acetyl CoA may build up

A

Indicates a well-fed state; produced from either

  • Pryuvate metabolism
  • B oxidation of fatty acids
  • Breakdown of ketogenic aa (Leu & Lys)
23
Q

What does acetyl CoA activate? Why?

A

Acetyl CoA activates pyruvate carboxylase because it’s a sign that more oxaloacetic acid is required for gluconeogenesis

Also remember that it was an inhibitor for pyruvate kinase.

24
Q

Adipocytes can’t perform gluconeogenesis. What is glyceroneogenesis?

A

Process by which glycerol-3-phosphate is generated from pyruvate in liver and adipose cells.

25
Q

High serum fatty acids correlate with ___ed insulin sensitivity

A

High serum FA –> reduced insulin sensitivity

26
Q

Why do some diabetes drugs stimulate glyceroneogenesis?

A

It re-esterifies fatty acis back into triglycerides among adipocytes to increase insulin sensitivity

27
Q

When glucagon is high, what do adipose tissues do?

A

Hydrolyze triglyceride fat stores into glycerol and free FA, released into the blood stream

  • Glycerol goes to liver as a precursor for gluconeogenesis
  • Free FAs are taken up by other tissues (like muscle) to be oxidized for energy to CO2
28
Q

Free fatty acids that aren’t metabolized go to the liver, where they get

A

Re-esterified to glycerol-3-phosphate from pyruvate during glyceroneogenesis to produce new triglycerides. These triglycerides are exported to the liver to provide FFAs to the fat cells, where new TGs can be synthesized and stored.

29
Q

Glyceroneogenesis uses pyruvate as a precursor and involves the enzymes pyruvate kinase and PEPCK; however, it doesn’t include F1,6BPase-1 or Glucose-6-phosphatase, so ___ backs up and is reduced to ___ by ____.

A

DHAP backs up and is reduced to glycerol 3-phosphate by glycerol 3-phosphate dehydrogenase.

gly 3 p is the final product of glyceroneogenesis

30
Q

Adipocytes lack ___, which is why glycerol from hydrolysis of TGs must travel to the liver in order to be phosphorylated to glycerol 3-phosphate.

A

glycerol kinase

31
Q

Rosiglitazone

A

Diabetes drug

Stimulates transcription PEPCK and thus induces glyceroneogenesis –> marked decrease in FFA release from adipose tissue (which usually happens in T2D)

32
Q
A
33
Q

Can your body make glucose from fatty caids? Can i tmake it from triglycerides?

A

B-oxidation of FA yields only acetyl-CoA

Wheras, triglycerides’ glycerol can be converted to glucose

34
Q

“Second wind” of long-distance runners / Cori cycle

A
  1. Muscles require ATP from glycogen breakdown.
  2. When oxygen is low, the pyruvate of glycolysis is converted to lactate to regenerate NAD+.
  3. Lactate is taken up by the liver, which converts it to glucose that goes back to the muscle to replenish glycogen supplies.
35
Q

What are teh energy requirements to make one glucose from 2 pyruvates? From 2 lactate molecules?

A

From 2 pyruvates: 4ATP + 2GTP + 2NADH

From 2 lactates: 4ATP + 2GTP

36
Q

Cortisol stimulates

A

Gluconeogenesis in the liver by increasing PEPCK synthesis and increasing protein breakdown for glucose synthesis.

37
Q

Why is it important to coordinately control glycolysis and gluconeogenesis?

A

Gluconeogenesis is energetically expensive, so your liver & kidneys shouldn’t be breaking down glucose via glycolysis when it’s needed to supply the brain.

The liver & other tissues can use FA for energy generation, but the brain can’t because BBB

38
Q

Pyruvate kianse is inactivated by glucagon-stimulated cAMP-dependent protein kinase. Why?

A

It takes 2 enzymes, an ATP, and a GTP to convert pyruvate back to PEP. When you have low blood sugar, inactivating pyruvate kinase makes the process of gluconeogenesis instead more energetically favorable

39
Q

Where dose glyceroneogenesis occur

A

adipose and liver tissue

Biochem (28 decks)

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