Lecture 31: TCA Cycle Regulation

Question 1

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

Answer 1

• Pyruvate Dehydrogenase Complex

- Citrate Synthase

Question 2

What are the two additional regulated reactions?

Answer 2

• Isocitrate dehydrogenase

- alpha-ketogluterate dehydrogenase complex

Question 3

What do all four regulated reactions have in common?

Answer 3

• highly exergonic

- keep the cycle going in a clockwise direction usually

Question 4

What happens if the four regulated steps are slowed?

Answer 4

the whole cycle will be slowed

Question 5

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

Answer 5

High concentrations of:
ATP
Acetyl-CoA
NADH
Succinyl-CoA
Citrate

Question 6

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

Answer 6

AMP
NAD+
CoA
ADP

-because they are substrates or they work through allosteric effects

Question 7

What inhibits the Pyruvate Dehydrogenase Complex?

Answer 7

ATP
Acetyl-CoA
NADH
Fatty Acids

Question 8

What activates the pyruvate dehydrogenase complex?

Answer 8

AMP
CoA
NAD+
Ca2+

Question 9

What inhibits reaction 1 of TCA cycle?

Answer 9

NADH
Succinyl-CoA
Citrate
ATP

Question 10

What activates reaction 1 of TCA cycle?

Answer 10

ADP

Question 11

What activates reaction 3 of TCA cycle

Answer 11

Ca2+

ADP

Question 12

What inhibits reaction 3 of TCA cycle

Answer 12

ATP

Question 13

What activates reaction 4 of TCA cycle?

Answer 13

Ca2+

Question 14

What inhibits reaction 4 of TCA cycle

Answer 14

Succinyl-CoA

NADH

Question 15

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

Answer 15

Ca2+:

• PHD
• Reaction 3
• reaction 4

Question 16

What regulates the Pyruvate Dehydrogenase complex activity? Explain

Answer 16

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

Question 17

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

Answer 17

HS-CoA

Question 18

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

Answer 18

Acetyl-CoA

Question 19

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

Answer 19

NAD+

Question 20

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

Answer 20

NADH

Question 21

What are two problems associated with the TCA cycle?

Answer 21

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

Question 22

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

Answer 22

Pyruvate
alpha-ketogluterate
Fumarate
Succinate
Aspartate

NOT OXALOACETATE AND ACETYL-COA

Question 23

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

Answer 23

Phosphoenolpyruvate
Citrate
Malate
Aspartate

Question 24

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

Answer 24

Catabolism of carbohydrates or fatty acids

Question 25

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

Answer 25

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

Question 26

Anaplerotic reactions

Answer 26

the reactions that replenish the metabolites in the citric acid cycle

Question 27

What is the main anaplerotic reaction?

Answer 27

replenishment of oxaloacetate

Question 28

Transporter for pyruvate

Answer 28

import only - need another way for export or another metabolite of its equivalent - PEP Transporter! for export

Question 29

Transporter for acetyl-CoA

Answer 29

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

Question 30

Acetyl-CoA

Answer 30

needed for fatty acid synthesis in the cytoplasm

Question 31

Malate and Aspartate shuttles

Answer 31

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

Question 32

What is another way that oxaloacetate can be exported?

Answer 32

to malate | -malate can leave or enter the mitochondrial matrix

Question 33

J. Glyoxylate cycle

Answer 33

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

Question 34

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

Answer 34

succinate which can be transferred to the TCA cycle