Metabolic Integration Flashcards

1
Q

Which FOUR reaction pathways covered in BIOL244 lectures are anabolic?

A
  • Gluconeogenesis
  • Glycogen biosynthesis
  • Lipid biosynthesis (fatty acid biosynthesis)
  • Amino acid biosynthesis
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2
Q

Which FOUR reaction pathways covered in BIOL244 lectures are catabolic?

A
  • Glycolysis
  • The TCA cycle (and ultimately oxidative phosphorylation)
  • β-oxidation (of fatty acids / lipid degredation)
  • Amino acid catabolism

The pentose phosphate pathway is also included but not covered.

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3
Q

List:

FOUR key hub metabolites that link the major pathways covered in BIOL244.

A
  • 4 sugar-phosphates
  • 3 α-ketoacids
  • 2 CoA derivatives
  • PEP (phosphoenolpyruvate)
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4
Q

Define:

Evolved coupling stoichiometry

A

The number of ATP molecules consumed/produced in a particular pathway.

A compromise, and consequence of evolution.

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5
Q

Define:

Obligate coupling stoichiometry

A

The stoichiometric coupling of redox reactions with electron carriers.

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6
Q

What changes about the ΔG° of pathways that generate more ATP than the evolved coupling stoichiometry.

A

They have progressively smaller negative ΔG° values overall, making them less and less thermodynamically favourable.

The evolved coupling stoichiometric amount of 38 (in prokaryotic cells) provides a high yield per glucose molecule, whilst still being low enough that almost all glucose is metabolised.

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7
Q

The overall thermodynamic efficiency of any metabolic sequence is determined by…

A

ATP coupling.

The involvement of ATP alters the ΔG of the reaction.

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8
Q

What helps ensure the [ATP] : [ADP] + [Pi] ratio stays high?

A

Kinetic controls over metabolic pathways.

Which allows ATP hydrolysis to power essentially any biochemical process.

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9
Q

What role does ATP serve as an allosteric effector?

A

Its concentration acts as an energy status index for the cell, and determines the rates of key allosterically-regulated enzymes at important points in metabolic pathways.

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10
Q

What is the stoichiometric role of ATP?

A

Establishing large equilibrium constants for metabolic conversions, and thus rendering them thermodynamically favourable.

As this, it acts as the energy currency of the cell.

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11
Q

What is the adenylate system/pool comprised of?

A

ATP, ADP, & AMP.

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12
Q

What “lies at the very heart of metabolism”?

A

Energy transduction and energy storage in the adenylate
system (pool)
.

This is ATP, ADP, and AMP.

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13
Q

Which enzyme provides a direct connection amongst the three molecules of the adenylate pool?

(ATP, ADP, and AMP)

A

Adenylate kinase

It catalyses the reversible phosphorylation of AMP by ATP.

ATP + AMP ⇌ 2ADP

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14
Q

How many phosphoanhydride bonds does ATP have?

A

2

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15
Q

How many phosphoanhydride bonds does ADP have?

A

1

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16
Q

How many phosphoanhydride bonds does AMP have?

A

0

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17
Q

What happens to the energy charge if [ATP] is high?

A

It approaches 1.

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18
Q

What happens to the energy charge if [ATP] is low?

A

It approaches 0.

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19
Q

How does energy charge affect metabolic regulation?

A

It contributes to the regulation of key enzymes.

(e.g. phosphofructokinase being allosterically inhibited by high concentrations of ATP, but stimulated by AMP).

20
Q

What is considered the cellular energy sensor?

A

AMP-activated protein kinase (AMPK)

21
Q

What happens when AMP binds to AMPK?

A

Its activity increases significantly.

More than 1000-fold!

AMP is its allosteric activator and promotes phosphorylation (activation).

22
Q

What happens when ATP binds to AMPK?

A

It promotes dephosphorylation and thus renders AMPK inactive.

23
Q

What happens when ADP binds to AMPK?

A

It protects AMPK from dephosphorylation.

24
Q

What is the function of AMPK in its active form?

A

It phosphorylates many protein targets controlling cellular energy production and consumption.

25
Q

List:

The THREE major fuel depots in animals.

A
  • Glycogen (liver & muscle)
  • Triglycerides (adipose tissue)
  • Protein (mostly skeletal muscle)

This is also the order for preference of use of these different energy stores.

26
Q

What is the major energy reservoir of the brain?

A

Nothing

This is why the brain consumes the most energy of all our organs.

27
Q

What is the major energy reservoir of the skeletal muscle (resting state)?

A

Glycogen

28
Q

What is the major energy reservoir of the skeletal muscle (strenuous activity)?

A

Nothing

This is when all of the energy stores have been consumed.

29
Q

What is the major energy reservoir of the heart muscle?

A

Glycogen

30
Q

What is the major energy reservoir of adipose tissue?

A

Triacylglycerols

(aka triglycerides)

31
Q

What are the TWO major energy reservoirs of the liver?

A

Glycogen & triacylglycerols

32
Q

What is the preferred substrate of the brain?

A

Glucose

But during starvation it can utilise ketone bodies.

33
Q

What is the preferred substrate of the skeletal muscle (resting state)?

A

Fatty acids

34
Q

What is the preferred substrate of the skeletal muscle (strenuous activity)?

A

Glucose from glycogen.

35
Q

What is the preferred substrate of the heart muscle?

A

Fatty acids

36
Q

What is the preferred substrate of adipose tissue?

A

Fatty acids

37
Q

What are the THREE preferred substrate of the liver?

A
  • Amino acids
  • Glucose
  • Fatty acids
38
Q

What energy sources are exported from the brain?

A

None

39
Q

What energy sources are exported from the skeletal muscle (resting state)?

A

None

40
Q

What energy sources are exported from the skeletal muscle (strenuous activity)?

A

Lactate

41
Q

What energy sources are exported from the heart muscle?

A

None

42
Q

What TWO energy sources are exported from adipose tissue?

A

Fatty acids & glycerol

43
Q

What THREE energy sources are exported from the liver?

A
  • Fatty acids
  • Glucose
  • Ketone bodies
44
Q

What is the major metabolic processing centre in vertebrates?

A

The liver.

45
Q

What hub metabolite does the activity of the liver centre around?

A

Glucose-6-phosphate

46
Q

What are the FIVE key fates of glucose-6-phosphate in the liver?

A
  • Converted to glycogen.
  • Released as blood glucose.
  • Used to **generate NADPH **and pentoses via the pentose phosphate
    pathway
    .
  • Catabolized to acetyl-CoA for fatty acid synthesis.
  • Energy production by oxidative phosphorylation.