-> TCA > ETC > OxPhoshporylation

Question 1

How does pyruvate enter the mitochondria?

Answer 1

Glycolysis in cytoplasm -> pyruvate
Pyruvate enters via the mitochondrial pyruvate carrier a transmembrane heterodimer.

Question 2

What are pyruvate dehydrogenase complexes responsible for?

Answer 2

Link reaction in mitochondira: Catalyses the committed step of pyruvate -> acetyl-CoA and NAD -> NADH

Question 3

How does pyruvate initially interact with PDC?

Answer 3

Via the substrate in PDC’s E1 subunit.

Question 4

How is PDC allosterically controlled?

Answer 4

Inhibition: The end products produced by PDC (acetyl CoA, NADH and ATP) inhibit PDC. High conc of end products = inactive PDC.
Activation: the binding substrates (pyruvate and ADP) will themselves promote the catalytic activity of the enzyme.

Question 5

How is PDC covalently modified?

Answer 5

Inactivation: a serine residue on the PDC is phosphorylated by PDC kinase (PDK). The covalent binding of Pi to the enzyme inhibits its activity.
Activation: the phosphorylated serine is hydrolysed by PDC phosphatase removing the Pi.

Question 6

When can the TCA cycle start?

Answer 6

When the concentration of acetyl-CoA / oxaloacetate is high enough.

Question 7

What are the main metabolites of the TCA cycle?

Answer 7

PDC reaction -> acetyl CoA enters cycle -> citrate -> oxaloacetate -> cycle repeats.

Question 8

What are the 4 enzyme reactions in the 1st phase of the TCA cycle in order?

Answer 8

1. Condensation of acetyl CoA with oxaloacetate to form citrate, this is catalysed by citrate synthetase. (condensation = two molecules combined into one)
2. Aconitase isomerises citrate to isocitrate
3. Isocitrate dehydrogenase decarboxylates isocitrate to give a-ketoglutarate. -> NADH + CO2
4. a-ketoglutarate dehydrogenase decarboxylates a-ketoglutarate to give succinyl Co-A and CO2 + NADH
   Condensation -> isomerisation -> decarboxylation x 2, 2 x CO2 and 2 x NADH are released from the decarboxylation.

Question 9

What are the 4 enzyme reactions in the second phase of the TCA cycle in order?

Answer 9

5. The co enzyme A of succinyl CoA is removed by succinate thiokinase to give succinate + GTP
6. Succinate is oxidised by succinate dehydrogenase to give give fumarate (FAD+ accepts hydrogen -> FADH2)
7. Fumarate is reduced by hydration forming malate and is catalysed fumarase.
8. Malate is oxidised via the reduction of NAD+ by malate dehydrogenase to give oxaloacetate and NADH

Question 10

What are the energy producing steps in the TCA cycle

Answer 10

3. • 4. 2 x decarboxylation -> 2 x NADH
4. Succinate oxidation -> FADH2
5. Malate oxidation -> NADH

Question 11

What does the electron transfer chain do?

Answer 11

Takes the released products of the TCA cycle and through a series of four protein complexes produces ATP via coupled redox reactions.

Question 12

What does complex 1 do in the ETC?

Answer 12

Complex 1 (NADH-Q oxireductase) first transfers e- from NADH to ubiquinone (Q)

Question 13

What does complex 2 do in the ETC?

Answer 13

Complex 2 (succinate-Q oxireductase) transfers e- from FADH2 to ubiquinone (Q)

Question 14

What does complex 3 do in the ETC?

Answer 14

Complex 3 (not gonna bother with the name) recieves electrons from Q

Question 15

What does complex 4 do in the ETC?

Answer 15

Cytochrome c receives e- from Q and transfers them to complex 4 (cytochrome c oxidase). Complex 4 then uses O2 as an oxidizing agent and reduces it by donating electrons producing water. (O2s receive the electrons at the end of ETC)

Question 16

What is the purpose of the ETC?

Answer 16

To transport protons from the mitochondrial matrix accross the inner membrane to the lumen via protein complexes 1-> 4 causing a H+ accumulation.

Question 17

What is the purpose of accumulating protons in the mitochondrial inner membrane space?

Answer 17

To catalyse the rotation of ATPase pumps (ADP + Pi = ATP)

Question 18

What is the overall result of the TCA cycle?

Answer 18

1 x acetyl CoA =
- 2 CO2
- 1 GTP
- 1 FADH2
- 3 NADH

Question 19

What happens in oxidative phosphorylation?

Answer 19

ETC -> 6 x O2 and (ADP + Pi) -> oxidative phosphorylation =
- 10 NAD+
- 2 FAD
- 12 H2O
-> ATP!

Question 20

In aerobic respiration approximately how many ATP molecules will be produced from 1 mol of glucose

Answer 20

~ 32 ATP

Question 21

What are the committed/irreversible steps of the TCA cycle? How are they controlled?

Answer 21

1. Citrate synthase
2. Isocitrate dehydrogenase
3. a-ketoglutarate dehydrogenase
   All are activated by Ca2+ ions (such as when a muscle contracts)
   The enzymes are also inhibited allosterically by ATP, cycle intermediates and NADH.