Lecture 31: TCA Cycle Regulation Flashcards

1
Q

What are the two main checkpoints for regulation in the TCA cycle?

A
  • Pyruvate Dehydrogenase Complex

- Citrate Synthase

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2
Q

What are the two additional regulated reactions?

A
  • Isocitrate dehydrogenase

- alpha-ketogluterate dehydrogenase complex

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3
Q

What do all four regulated reactions have in common?

A
  • highly exergonic

- keep the cycle going in a clockwise direction usually

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4
Q

What happens if the four regulated steps are slowed?

A

the whole cycle will be slowed

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5
Q

What effectors are associated with energy-rich state of the cell?

A
High concentrations of:
ATP
Acetyl-CoA
NADH
Succinyl-CoA
Citrate
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6
Q

What effectors are associated with energy-poor state of the cell?

A

AMP
NAD+
CoA
ADP

-because they are substrates or they work through allosteric effects

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7
Q

What inhibits the Pyruvate Dehydrogenase Complex?

A

ATP
Acetyl-CoA
NADH
Fatty Acids

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8
Q

What activates the pyruvate dehydrogenase complex?

A

AMP
CoA
NAD+
Ca2+

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9
Q

What inhibits reaction 1 of TCA cycle?

A

NADH
Succinyl-CoA
Citrate
ATP

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10
Q

What activates reaction 1 of TCA cycle?

A

ADP

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11
Q

What activates reaction 3 of TCA cycle

A

Ca2+

ADP

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12
Q

What inhibits reaction 3 of TCA cycle

A

ATP

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13
Q

What activates reaction 4 of TCA cycle?

A

Ca2+

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14
Q

What inhibits reaction 4 of TCA cycle

A

Succinyl-CoA

NADH

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15
Q

What is an allosteric activator of 3 of the four regulated steps? and which steps?

A

Ca2+:

  • PHD
  • Reaction 3
  • reaction 4
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16
Q

What regulates the Pyruvate Dehydrogenase complex activity? Explain

A

In mammals (not in smaller eukaryotes or prokaryotes) Phosphorylation of the E1 subunit

  • There is a kinase activity that can either put on or off the E1 subunit a phosphate
  • The kinase and phosphatase activites are controlled by the metabolites associated with energy wealth or poverty (ANTOEHR WAY TO CONTROL PDH)
  • NAD+, CoA, ADP, and pyruvate inhibit the kinase so the PDH complex is active
  • NADH, Acetyl-CoA induce the kinase, so the PDH complex becomes more phosphorylate and is inactive
17
Q

What activates the activity of the E2 subunit of the pyruvate dehydrogenase complex?

A

HS-CoA

18
Q

What inhibits the activity of the E2 subunit of the pyruvate dehydrogenase complex?

A

Acetyl-CoA

19
Q

What activates the activity of the E3 subunit of the pyruvate Dehydrogenase complex?

A

NAD+

20
Q

What inhibits the activity of the E3 subunit of the pyruvate dehydrogenase complex?

A

NADH

21
Q

What are two problems associated with the TCA cycle?

A

1) the cycle has to have a way to run without buildup or depletion of intermediates even if there is extensive injection or withdrawal of different components
2) Most of the catabolic and anabolic reactions take place in the cytoplasm. The TCA cycle takes place in the inside the inner membrane of the mitochondrial matrix from pyruvate onwards. THERE ARE NO TRANSPORT CHANNELS FOR ALL OF THE COMPOUNDS

22
Q

What input channels exist for the TCA cycle allowing metabolites in?

A
Pyruvate
alpha-ketogluterate
Fumarate
Succinate
Aspartate

NOT OXALOACETATE AND ACETYL-COA

23
Q

What output channels exist for the TCA cycle allowing metabolites out?

A

Phosphoenolpyruvate
Citrate
Malate
Aspartate

24
Q

What is the reason why a high amount of metabolites would enter the TCA cycle?

A

Catabolism of carbohydrates or fatty acids

25
Q

What happens if there isn’t any carbohydrate available due to the conversion of pyruvate to fatty acids?

A

-deficiency of acetyl-CoA entering the citric acid cycle. Therefore oxaloacetate can exceed its normal concentration in the mitochondrion and will be exported

26
Q

Anaplerotic reactions

A

the reactions that replenish the metabolites in the citric acid cycle

27
Q

What is the main anaplerotic reaction?

A

replenishment of oxaloacetate

28
Q

Transporter for pyruvate

A

import only

  • need another way for export or another metabolite of its equivalent
  • PEP Transporter! for export
29
Q

Transporter for acetyl-CoA

A

None for export

  • Citrate can be formed with a reaction of oxaloacetate which can be exported
  • once citrate is exported into the cytoplasm-its decomposed to oxaloacetate and acetyl-CoA by the enzyme ATP-citrate lyase
30
Q

Acetyl-CoA

A

needed for fatty acid synthesis in the cytoplasm

31
Q

Malate and Aspartate shuttles

A

antiports

  • malate antiports with alpha-ketogluterate, fumarate, or succinate
  • aspartate antiportss with glutamate
32
Q

What is another way that oxaloacetate can be exported?

A

to malate

-malate can leave or enter the mitochondrial matrix

33
Q

J. Glyoxylate cycle

A

in microorganisms and plants

  • uses two molecules of Acetyl-CoA and does not release CO2 in each cycle
  • results in efficient biosynthesis of oxaloacetate
  • self-sustaining
34
Q

what is the output of the J. Glyoxylate cycle? (PRODUCT)

A

succinate which can be transferred to the TCA cycle