Citric Acid Cycle and Oxidative Phosphorylation

Question 1

What enzyme of the cycle uses as coenzyme and cofactors thiamine, lipoic acid, CoA, FAD, NAD?, what other important enzymes use them?

Answer 1

Alfa-ketoglutarate dehydrogenase
- pyruvate dehydrogenase, branched-chain ketoacid dehydrogenase (BCAA metabolism)
“Tending Loving Care For Nancy” TLCFN enzymes

Question 2

What happen in Krebs cycle if thiamine deficiency?

Answer 2

Slow oxidation of acetyl-CoA

Alfa-ketoglutarate DH doesn’t work

Question 3

What intermediate can be used to produce ATP equivalent (GTP) in Krebs cycle by substrate level phosphorylation?

Answer 3

Succinyl-CoA by succinyl-CoA synthetase

Question 4

What substances can block complex I (NADH DH)?

Answer 4

Barbiturates
Rotenone (insecticide)

Question 5

What translocate the H+ (protons) from the matrix to the intermembrane space while the “electricity” (electrons captured) passes to creat the proton gradient?

Answer 5

The same three major complexes that accept and pass the electrons (proton pumps - translocators)
- complexes I, III, IV (NADH DH, cytochrome b/c, cytochrome a/a3)

Question 6

What are the 3 shuttle systems and their functions?

Answer 6

.

Question 7

What is the result of an inhibitor?

Answer 7

“DID”

• ⬇️ O2 consumption
• ⬆️ NADH/NAD, FADH2/FAD ratios
• ⬇️ ATP

Question 8

Treatment for cyanide poisoning

Answer 8

*Nitrites - Hb ➡️ methb ▶️ binds cyanide before reach tissue
Or thiosulfate + cyanide ➡️ thiocyanyde (less toxic)
*Oxygen

Question 9

Overall, what is control of Krebs cycle?

Answer 9

Energy status of the cell exert the control

Question 10

What are the effects of the uncouplers?

Answer 10

• ⬇️ proton gradient - ⬆️ rate of the ETC
• ⬇️ ATP synthesis
• ⬆️ O2 consumption
• ⬆️ NADH oxidation

Question 11

Natural uncoupler and its function

Answer 11

Thermogenin - energy loss as heat to maintain body temperature (brown adipose tissue) in newborns and very low T

Question 12

What is the defense against the reactive oxygen species? Causes of ROS?

Answer 12

Superoxide dismutase, catalase, glutathione peroxidase, vitamin E, C, NADPH

• deficiency in one of them - hemolysis (ex, G6P DH def - ⬇️ NADPH)
• reperfusion injury ▶️ O2 suddenly introduced - burst in ETC ▶️ ⬆️ ROS

Question 13

Key characteristics of most mitochondrial diseases, main organ affected?

Answer 13

• lactic acidosis and ragged red fibers (massive proliferation of mitochondria in muscle)
• highly aerobic tissues (nerves, muscles)
• maternal inheritance

Question 15

What part of the ECT does doxorubicin block? Symptoms

Answer 15

Bind to coenzyme Q 10 - stop the ETC

headache, tachycardia, tachypnea, nausea, disorientation