Lecture 31

Question 1

What are the two main checkpoints in TCA (citric acid cycle)?

Answer 1

• pyruvate Dehydrogenase complex

- citrate synthase

Question 2

What are two other regulated reactions other than the two main checkpoints in the TCA cycle?

Answer 2

• isocitratre dehydrogenase

- a-ketogluterate dehydrogenase complex

Question 3

What do all the four regulated reactions in the TCA cycle have in common?

Answer 3

• Highly exergonic
• these reactions keep the cycle going (usually) in a clockwise direction
• if the flow of metabolites at these reactions is slowed the whole cycle will slow down

Question 4

What is associated with the energy rich state of the cell?

Answer 4

High Concentrations of ATP, acetyl-CoA, NADH, succinyl-CoA, and citrate

Question 5

What is associated with energy poor state of the cell?

Answer 5

• these are your activators because they are substrates or because they work through allosteric effects
• AMP, NAD+, CoA, ADP

Question 6

What is an allosteric activator at three of the four regulator steps?

Answer 6

Ca2+

Question 7

What inhibits PHD?

Answer 7

ATP, Acetyl-CoA, NADH, and Fatty Acids

Question 8

What activates PHD?

Answer 8

AMP, CoA, NAD+, Ca2+

Question 9

what inhibits citrate synthase?

Answer 9

NADH, succinyl-CoA, citrate, ATP

Question 10

What activates citrates synthase?

Answer 10

ADP

Question 11

What inhibits isocitrate dehydrogenase?

Answer 11

ATP

Question 12

What activates isocitrate dehydrogenase?

Answer 12

Ca2+, ADP

Question 13

What inhibits a-ketogluterate dehydrogenase complex?

Answer 13

Succinyl-CoA, NADH

Question 14

What activates a-ketogluterate dehydrogenase complex?

Answer 14

Ca2+

Question 15

PDH complex covalent modification?

Answer 15

• In mammals but not in smaller eukaryotes or prokaryotes
• phosphorylation of the E1 subunit regulates the activity
• there is kinase and a phosphatase activity that puts on or takes off a phosphate on the E1 subunit

Question 16

What would put the PDH complex in the active state?

Answer 16

NAD+, CoA, ADP, and pyruvate inhibit the kinase activities the PDH complex tends to the unphosphorylated state-active state

Question 17

What would put the PDH complex in the inactive State?

Answer 17

NADH, Acetyl-CoA induce the kinase, so the PDH complex becomes more phosphorylated and is inactive

Question 18

What regulates the activity of the pyruvate dehydrogenase complex subunits E2 and E3

Answer 18

• by the concentrations of NAD+/NADH and HS-CoA/Acetyl-CoA
• NAD+ activates E3
• NADH inhibits E3
• HS-CoA activates E2
• Acetyl-CoA inhibits E2

Question 19

In the TCA cycle what input channels are there?

Answer 19

Pyruvate
a-ketogluterate
Fumurate 
Succinate
Aspartate

BUT NOT Oxaloacetate nor acetyl-CoA

Question 20

In the TCA cycle was output channels are there?

Answer 20

phosphoenolpyruvate
citrate
malate
Aspartate

Question 21

What is the most likely reason that high amounts of metabolites would enter the TCA cycle?

Answer 21

from catabolism of carbohydrates or fatty acids (ex: from the diet)

Question 22

anaplerotic reactions

Answer 22

the reactions that replenish the metabolites in the citric acid cycle

Question 23

What is the main anaplerotic reaction?

Answer 23

replenishment of oxaloacetate

Question 24

What side of the TCA cycle does the metabolites needed for anabolic reactions come from? What is the consequence of any withdrawel from this?

Answer 24

Right side of the TCA cycle

-decrease in the oxaloacetate concentration

Question 25

Glyoxylate cycle

Answer 25

in microorganisms and plants

• uses two molecules of acetyl-CoA in each cycle and does not release CO2
• results in efficient biosynthesis of oxaloacetate
• succinate is produced and is transferred to the citric acid cycle

Question 26

Where does the TCA cycle occur?

Answer 26

eukaryotes-mitochondrial matrix

bacteria-cytosol

Question 27

What is gained per each cycle of the TCA cycle?

Answer 27

for each acetyl-CoA oxidized by the cycle, the energy gain is three NADH, one FADH2, and one ATP(GTP)

Question 28

Mitochondrion

Answer 28

has two bilayer membranes

-outer and inner membrane

Question 29

Phase 1 of catabolism is located where?

Answer 29

Glycolysis-to the point of pyruvate takes place in the cytoplasm
-outside of the outer membrane of the mitochondrion

Question 30

Outer membrane of mitochondrion

Answer 30

-porous thus is easy equilibration of material from the cytoplasm across the outer membrane into the inter membrane space

Question 31

Inner membrane of mitochondrion

Answer 31

75% protein by weight

-completely closed and transporters are needed for movement of molecules

Question 32

Phase 2 of catabolism

Answer 32

citric acid cycle plus fatty acid oxidation and acid degradation

• takes place in the inner membrane of the mitochondria
• reduced electron carriers (NADH and FADH) will accumulate inside the inner membrane

Question 33

Entry of Pyruvate into the TCA cycle

Answer 33

• called oxidative decarboxylation because CO2 is lost from pyruvate and there is oxidation
• enzyme: pyruvate dehydrogenase complex

Question 34

Pyruvate dehydrogenase

Answer 34

• enzyme used to covert pyruvate to acetyl-CoA

- contains three types of subunits (E1, E2, and E3)

Question 35

E1 subunit of pyruvate dehydrogenase complex

Answer 35

pyruvate dehydrogenase

-coenzyme: TDP (aka TPP)

Question 36

E2 subunit of pyruvate dehydrogenase complex

Answer 36

dihydrolipoamide acetyltransferase

-coenzyme:lipollysine

Question 37

E3 subunit of pyruvate dehydrogenase complex

Answer 37

dihydrolipoamide dehydrogenase

-coenzyme: FAD

Question 38

Reaction 1 of TCA cycle

Answer 38

enzyme: Citrate synthase
- Acetyl-CoA is a high energy compound and it is used as a substrate contributor to the large standard free energy decrease making the reaction and irreversible one

Question 39

Succinate Dehydrogenase

Answer 39

-located in the inner side of the inner mitochondrial membrane