ML9: Glycogenesis and gluconeogenesis Flashcards

1
Q

What happens to food fuel supplies that exceed immediate needs?

A

Carbohydrates: stored as glycogen

Lipids: stored as TAGs

Proteins: not stored but can be converted to lipids and stored if necessary

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2
Q

Where is the majority of fuel stored in the human body?

A

Adipose tissue (lipids), muslce (protein and glycogen), and liver (glycogen)

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3
Q

What is the largest energy store in humans?

A

Lipids (triacylglycerols)

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4
Q

When is muscle protein broken down?

A

During prolonged starvation

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5
Q

How is glucose stored in the body? Give facts about this molecule.

A

As glycogen

High molecular weight polymers (107 – 108)

Highly polar so attracts H2O (this limits storage)

No specialised storage tissue (stored in granules in muscle and liver)

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6
Q

How is glycogen used in skeletal muscle?

A

Skeletal muscles are designed to contract and provide mechanical power

Glycogen is used to power contraction

It is converted to glucose-1P, then glucose-6P, then undergoes glycolysis to form ATP, lactate, and CO2

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7
Q

How is glycogen used in the liver?

A

The liver is used as a reservoir of glycogen and stores reserve glycogen for release as glucose when blood sugar is low

Glycogen is converted to glucose-1P then glucose-6P, then is broken down by glucose-6-phosphatase into glucose so that it can be released into the blood. Gluconeogenesis also raises blood glucose levels.

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8
Q

How is glycogen made?

A

Glycogen synthase (makes a straight chain) adds glucosyl residues from UDP-glucose

It catalyses α-1,4 linkages

Approx. 7 residues are transferred and joined via α-1,6 linkages by a branching enzyme

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9
Q

How is glycogen broken down?

A

Glycogen phosphorylase removes glucose-1-phosphate units

Glycogen phosporylase can only break α-1,4 linkages

Approx. 3 residues are transferred onto another branch by transferase

Glucosidase breaks α-1,6 linkages

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10
Q

Why are different pathways and enzymes involved in glycogen synthesis and breakdown?

A

With separate pathways and enzymes, it is possible to control processes separately, otherwise the cycle would just be continuous and energy would be lost

There is a ‘sliding scale’ of activity of synthesis and breakdown – not 100% on or off, but tightly regulated

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11
Q

Explain the reciprocal regulaton of glycogen synthesis and breakdown.

A

When glucagon or adrenaline is secreted, glycogen synthases decrease in quantity, whilst phosphorylases increase and inhibit

When insulin is secreted, glycogen synthases increase and amplify the signals, whilst phosphorylases decrease

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12
Q

Which organ is primarily affected by glycogen storage diseases?

A

Liver

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13
Q

What happens if we run out of glycogen?

A

There is only enough liver glycogen for 8-12 hours

Skeletal muscle glycogen cannot be used to maintain plasma glucose because G6P cannot be released from the muscle cells (it lacks glucose-6-phospatase)

New glucose must be synthesised by the body through a process called gluconeogenesis

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14
Q

What is gluconeogenesis? Where does it take place?

A

Synthesis of glucose from (mainly) non-carbohydrate sources

Occurs in the liver (and kidney cortex)

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15
Q

Why is gluconeogenesis necessary?

A

The liver only has enough glycogen for 8-12 hours so runs out

Some tissues are totally dependent on glucose, such as RBCs, WBCs, kidney medulla and the lens of eye

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16
Q

What are the equivalents of hexokinase and phosphofructokinase in gluconeogenesis?

A

Hexokinase → glucose-6-phosphatase

Phosphofructokinase → fructose-1,6-bisphosphatase

17
Q

Why is gluconeogenesis not just a reversal of glycolysis?

A

Alternative reactions must occur to overcome the irreversible reactions in glycolysis

18
Q

Which steps are unique to gluconeogenesis?

A
  • Pyruvate carboxylase
    • pyruvate + CO2 + ATP + H2O → oxaloacetate + ADP + Pi + 2H
  • Phosphoenolpyruvate carboxykinase (PEPCK)
    • oxaloacetate + GTP + 2H+ → phosphoenolpyruvate + GDP + CO2
  • Glucose-6-phosphatase
    • glucose-6-phosphate + H2O → glucose + Pi
  • Fructose-1,6-bisphosphatase
    • fructose-1,6-bisphosphate + H2O → fructose-6-phosphate + Pi
19
Q

What are the substrates in gluconeogenesis?

A
  • Lactate from anaerobic glycolysis
    • Lactate is a metabolic dead-end so must be converted to pyruvate to be useful
  • Amino acids
    • alanine → pyruvate using alanine aminotransferase
  • Glycerol from TAGs
    • glycerol → glycerol-3-phosphate → dihydroxyacetone phosphate
20
Q

Is the reaction converting pyruvate to acetyl-CoA reversible or irreversible?

A

Irreversible

Cycling of acetyl-CoA through the citric acid cycle results in the loss of two carbon atoms as CO2

21
Q

How is gluconeogenesis regulated?

A

Reciprocally to the regulation of glycolysis

e.g. F-2,6-BP enhances glycolysis but inhibits gluconeogenesis

Phosphofructokinase is inhibited by high concentrations of ATP