Regulation of carbohydrate metabolism Flashcards

1
Q

Irreversible pathways in glycolysis

A

Glucose to G6P [Hexokinase]

F6P to FBP [PFK-1]

PEP to pyruvate [Pyruvate kinase]

These steps differ in gluconeogenesis

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2
Q

Carbon skeletons used in gluconeogenesis

A

Lactate [glycolysis]

Amino acids [proteins]

Glycerol [lipids]

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3
Q

Steps in gluconeogenesis [different from glycolysis]

A

G6P—> glucose
- G6Pase

F-1, 6-P2——> F6P
- Fruc-1,6-bishophatase

Pyruvate —-> Oxaloacetate
- Pyruvate carboxylate

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4
Q

Allosteric inhibition of PFK-1

A

ATP- indicates high energy levels

High H+

  • Indicates a lot of lactate production.
  • Prevents further damage from pH.
  • In the heart, high H+ is overcome by high AMP, leading to damage.
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5
Q

Allosteric activation of PFK-1

A

AMP

  • Indicates ATP levels.
  • Competes with ATP
  • Can overcome inhibition by H+ at high levels.
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6
Q

Nutrient allosteric activator of PFK-1.

A

F6P
- indicates glucose catabolism

Fruc-2,6-P2

  • indicates high F6P metabolism.
  • Most potent PFK-1 allosteric activator.
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7
Q

Nutrient allosteric inhibitor of PFK-1.

A

Citrate

- When in excess, indicates TCA cycle overload due to acetyl CoA build up.

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8
Q

PFK-2

A

Enzyme that converts F6P to Fructose-2,6-bisphosphate [Fruc-2,6-P2]

Part of a single tandem enzyme with Fructose-2,6-bisphosphatase.

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9
Q

G6-Pase

A

Enzyme used in gluconeogenesis.

Convertes G6P to glucose.

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10
Q

Fructose-1, 6-bisphosphatase

A

Enzyme used in gluconeogenesis.

Converts Fructose-1, 6-bisphosphate to F6P.

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11
Q

Pyruvate carboxylase

A

Enzyme used in gluconeogenesis.

Converts pyruvate to oxaloacetate.

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12
Q

Phosphoenolpyruvate carboxykinase

A

Enzyme used in gluconeogenesis.

Converts oxaloacetate to PEP

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13
Q

Fructose-2,6-bisphosphate

A

Product made from F6P using PFK-2 [6-phosphofructo-2-kinase]

The most potent allosteric activator of PFK-1.

Most potent inhibitor of fructose-1,6-bisphosphatase.

Not a metabolite- only use to reinforce allosteric control of PFK-1.

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14
Q

Control of PFK-1 and F-1,6-BPase

A

These enzymes are not controlled by hormone regulation.

- Instead the level of F-2,6-BP.

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15
Q

Fructose-2,6-Bisphosphatase

A

Enzyme that facilitates the conversion of Fructose-2,6-Bisphosphate to F6P.

Part of a single tandem enzyme with PFK-2.

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16
Q

Regulation of Fructose-2,6-Bisphosphatase

A

Phosphorylation stimulates its activation.
- Carried out by cAMP activated protein kinase.

  • Glucagon stimulates cAMP increase

Activation stimulates gluconeogenesis as F-2,6-BP is converted to F6P.

17
Q

Regulation of PFK-2

A

Phosphorylation deactivates PFK-2.
- Stimulated by glucagon action which increases cAMP.

Prevents conversion of F6P to F-2,6-BP.

This inhibits PFK-1.

Stimulates gluconeogenesis:
Stimulates F-1,6-BPase.

18
Q

Allosteric action of Acetyl CoA

A

Allosteric activator of pyruvate carboxylase.
[ Pyruvate to oxaloacetate]

Inhibits pyruvate dehydrogenase.
[Pyruvate to acetyl CoA]

So why Acetyl CoA is high, it favours gluconeogenesis over glycolysis.

19
Q

Glucagon effect on gluconeogenesis

A

Glucagon stimulates an increase in cAMP, activating cAMPPK.

Therefore it supports gluconeogenesis by:

  • Activating Fruc-2,6-BPase.
  • Deactivating PFK-2.
20
Q

Inhibitors of hexokinase

A

G6P

- Feedback inhibition to prevent XS build up of G6P

21
Q

Inhibitors of PFK-1

A

H+

Citrate

ATP

22
Q

Activators of PFK-1

A

AMP
- low ATP levels

Fruc-2,6-BP

23
Q

Inhibitors of Fruc-1,6-BPase

A

ATP

Fruc-2,6-BP

24
Q

Inhibition of pyruvate kinase

A

Inhibited when it is dephosphorylated.

Inhibited by high ATP levels
- Indicates high energy levels

25
Q

Activators of pyruvate kinase

A

Activated when phosphorylated.

Fruc-1,6-BP also activates allosterically.

26
Q

Activators of Pyruvate carboxylate

A

Activated by Acetyl-CoA.

- Indicates TCA overload, stimulating gluconeogenesis

27
Q

Urea cycle

A

Amino acids are transaminated before being converted to make glucose.
- Removes ammonia.

Ammonia is converted to urea in the liver and excreted by the liver
- Produces fumarate which enters the Kreb’s cycle.

Fumarate is converted to oxolacetate to be used in gluconeogenesis

Increase gluconeogenesis = Increase urea synthesis.

28
Q

Difference in F-2,6-BP utilisation in liver and muscle.

A

Muscle
- Uses glucose and glycogen to drive F-2,6-BP production which drives glycolysis.

Liver

  • Glycolysis is inhibited so F-2,6-BP production is inhibited.
  • Uses glucose from gluconeogenesis and glycogen to maintain blood glucose level.