Mitochondrial Metabolism

Question 1

Key Regulatory Steps in TCA Cycle

Answer 1

Question 2

During exercise, stimulation of the TCA cycle results principally from . . .

Answer 2

Decrease in the NADH/NAD+ ratio

Like pyruvate dehydrogenase, a major regulator of the flux through the TCA cycle is the NADH/NAD+ ratio. If this ratio is high, it means that little NAD+ is available to act as a cofactor in the oxidative steps of the cycle. This will tend to slow down the cycle.

Question 3

Two mitochondrial enzymes involved in generation of NADH that bear remarkable structural homology are. . .

Answer 3

pyruvate dehydrogenase and α-ketoglutarate dehydrogenase

Question 4

Oxaloacetate may. . .

Answer 4

. . .participate in the TCA cycle, or exit the mitochondrion to be decarbocylated and used as fodder for gluconeogenesis.

If energy levels are low, it will enter the TCA cycle to meet the energy demand via oxidative phosphorylation.

If energy levels are sufficient in the fasting state (which, remember, is mostly powered by fat-derived acetyl-CoA), it will exit the mitochondrion to take place in gluconeogenesis.

Question 5

Thiamine pyrophosphate

Answer 5

Question 6

Fates of pyruvate

Answer 6

Question 7

Regulation of pyruvate dehydrogenase

Answer 7

Question 8

The conversion of pyruvate to acetyl-coA results in production of ___, but conversion of amino acids to acetyl-coA does not.

Answer 8

The conversion of pyruvate to acetyl-coA results in production of carbon dioxide, but conversion of amino acids to acetyl-coA does not.

Question 9

Most ETC-derived ROS is generated in. . .

Answer 9

. . .complexes I and III.

Question 10

Other metabolic intersections with the TCA cycle

Answer 10

Question 11

Regulation of PDH in the fasted state

Answer 11

Question 12

Overview of TCA cycle

Answer 12

Question 13

Overview of Mitochondrial Metabolism

Answer 13

Question 14

α-ketoglutarate dehydrogenase

Answer 14

Question 15

TCA Cycle from 1000 ft

Answer 15

Question 16

Amino Acid Catabolism via the TCA cycle

Answer 16

Question 17

Destructive ROS cycle

Answer 17

Question 18

Citrate synthase

Answer 18

Question 19

Lipoic acid

Answer 19

Question 20

In the fasted state, pyruvate is primarily. . .

Answer 20

. . .conserved for gluconeogenesis. The fasted state relies on fat-derived acetyl-coA to power the citric acid cycle.

Question 21

ETC Complex I

Answer 21

Question 22

Uncoupling proteins

Answer 22

Question 23

ATP synthase

Answer 23

Question 24

A higher proton gradient, while speeding up ATP synthase activity, . . .

Answer 24

slows the rate of the electron transport chain, as complex I, III, and IV must now compete with with the proton gradient in order to pump their protons across.

Question 25

The most reactive form of ROS

Answer 25

hydroxyl radicals

Question 26

Regulation of PDH in the fed state

Answer 26

Question 27

Structure of pyruvate dehydrogenase

Answer 27

Question 28

Prosthetic groups of pyruvate dehydrogenase

Answer 28

Question 29

More detailed TCA cycle

Answer 29

Question 30

Mitochondrial ROS generation is most likely to happen in coditions of. . .

Answer 30

**NADH production higher than sufficient** to meet the ATP needs of the cell. This is because the proton gradient will be excessive, and lead to ETC slowing. **When the ETC is slowed down, it is more prone to ROS generation at complex I and III**. **This can be protected against by halting NADH generation when ATP needs are met**.

Question 31

The Electron Transport Chain

Answer 31

Question 32

\_\_\_% of ROS in the human body comes from the electron transport chain.

Answer 32

**85**% of ROS in the human body comes from the electron transport chain.

Question 33

In metabolism, cells always prioritize \_\_\_.

Answer 33

In metabolism, cells always prioritize **sufficient intracellular ATP**.

Question 34

Citrate may be utilized for ____ in addition to its role in the TCA cycle.

Answer 34

Citrate may be utilized for **fatty acid synthesis** in addition to its role in the TCA cycle.

Question 35

Final Steps of TCA cycle

Answer 35

Question 36

If Acetyl-CoA levels are high, and ATP/NADH levels are high, \_\_\_. If Acetyl-CoA levels are high, but ATP/NADH levels are low, \_\_\_.

Answer 36

If Acetyl-CoA levels are high, and ATP/NADH levels are high, **pyruvate carboxylase and PEP carboxykinase will both activate, stimulating gluconeogensis**. If Acetyl-CoA levels are high, but ATP/NADH levels are low, **pyruvate carboxylase, but not PEP carboxykinase, will activate, stimulating oxaloacetate generation and re-entry of oxaloacetate into the TCA cycle**.

Question 37

Pyruvate dehydrogenase is activated by \_\_\_.

Answer 37

Pyruvate dehydrogenase is activated by **NAD⁺**.

Question 38

Adenylate kinase

Answer 38

Converts two ADP to one ATP and one AMP. When you are severely depleted of oxygen, ADP levels go down. This is because under severe energy depletion, two ADPs will be converted into ATP and AMP

Question 39

In an uncoupled state, the ETC will move. . .

Answer 39

**faster​** in part because they are pumping against less of a gradient → less work, less of a thermodynamic barrier

Question 40

Dimethyl malonate

Answer 40

Currently under trials to mitigate damage during ischemia reperfusion injury. Blocks the activity of succinate dehyrogenase.

Question 41

The link between complexes I, II, and III

Answer 41

Ubiquinone

Question 42

Ischemia reperfusion injury

Answer 42

ischemia → succiante buildup reperfusion → e- overload, massive complex I ROS generation