Lecture 17: TCA Cycle and Oxidative Phsphorylation

Question 1

While oxygen is not directly required for TCA cycle, it is required for the _________ of coenzymes that are reduced in the cycle

Answer 1

While oxygen is not directly required for TCA cycle, it is required for the re-oxidation of coenzymes that are reduced in the cycle

Question 2

_____________:

A sequence of reactions that oxidizes acetyl CoA to CO2 and reduces nucleotides FAD or NAD to FADH2 and NADH respectively.

Answer 2

Krebs or Tricarboxylic Acid (TCA) Cycle:

A sequence of reactions that oxidizes acetyl CoA to CO2 and reduces nucleotides FAD or NAD to FADH2 and NADH respectively.

Question 3

Krebs Cycle Key Enzymes

Answer 3

Question 4

Krebs Cycle yields ____ electrons for Electron Transport Chain

____ FADH2 and ___ NADH

Answer 4

Krebs Cycle yields 8 electrons for Electron Transport Chain

1** FADH2 and **3 NADH

Question 5

TCA (Krebs) Cycle:

• Shared pathway for the metabolism of all fuels
• Oxidatively strips electrons from ________which is the common product of catabolism of fat, protein, and carbohydrate

Answer 5

TCA (Krebs) Cycle:

• Shared pathway for the metabolism of all fuels
• Oxidatively strips electrons from acetyl CoA which is the common product of catabolism of fat, protein, and carbohydrate

Question 6

TCA cycle functions

• _____________
• _____________

Answer 6

TCA cycle functions

• Energy production
• Biosynthesis

Question 7

Oxidation:

• The loss of ________
• The gain of ________

Reduction:

• The gain of ________
• The loss of ________

Answer 7

Oxidation:

• The loss of Electrons/Hydrogen
• The gain of Oxygen

Reduction:

• The gain of Electrons/Hydrogen
• The loss of Oxygen

Question 8

Answer 8

The TCA cycle produces reduced coenzymes by four redox reactions per cycle

• Three reactions produce NADH and another produces flavin adenine dinucleotide (FADH2).

These reduced molecules get re-oxidised during the electron transport chain and are essential for ATP production.

• Each mole of NADH produces ~2.5 mole ATP in the electron transport chain.
• Every FADH2 produces ~1.5 mole ATP in the electron transport chain.

Question 9

TCA cycle – interconversion of fuels and metabolites

• TCA cycle plays an important role in the synthesis of ________ from amino acids and lactate during starvation and fasting
• Conversion of carbohydrates to _______
• Source of nonessential amino acids (_______ and ________)
• Succinyl CoA serves as a precursor to ___________ in all cells
• TCA cycle begins with________ and not pyruvate as proteins and fat can contribute this to the cycle independent of pyruvate

Answer 9

TCA cycle – interconversion of fuels and metabolites

• TCA cycle plays an important role in the synthesis of glucose from amino acids and lactate during starvation and fasting
• Conversion of carbohydrates to fat
• Source of nonessential amino acids (aspartate** and **glutamate)
• Succinyl CoA serves as a precursor to porphyrins (heme) in all cells
• TCA cycle begins with acetyl CoA and not pyruvate as proteins and fat can contribute this to the cycle independent of pyruvate

Question 10

TCA (Krebs) Cycle Occurs in the ___________

Answer 10

TCA (Krebs) Cycle Occurs in the Mitochondrial Matrix

Question 11

The primary fate of acetyl CoA is oxidation in the TCA cycle but in the cytoplasm, it is used for generation of _______ and ______.

Answer 11

Primary fate of acetyl CoA is oxidation in the TCA cycle but in the cytoplasm is used for generation of Fatty Acids** and **Cholesterol.

Question 12

Answer 12

Question 13

Answer 13

Question 14

Answer 14

Question 15

Beriberi Disease –_________________Deficiency:

• High-output congestive heart failure and neurological symptoms are strongly suggestive of beriberi
• _________ pyruvate dehydrogenase activity
• Also slows down _________ at α- ketoglutarate dehydrogenase step
• Shunting of pyruvate to lactate results in lactic acidosis
• ______ beriberi – heart function and heart failure effected
• ______ beriberi damages nerves and can lead to a loss of muscle strength and paralysis
• _______ can make it difficult to absorb and store Vitamin B1

Answer 15

Beriberi Disease –Thiamine (Vitamin B1) Deficiency:

• High-output congestive heart failure and neurological symptoms are strongly suggestive of beriberi
• Decreases pyruvate dehydrogenase activity
• Also slows down the TCA cycle at α- ketoglutarate dehydrogenase step.
• Shunting of pyruvate to lactate results in lactic acidosis
• Wet beriberi – heart function and heart failure effected
• Dry beriberi damages nerves and can lead to a loss of muscle strength and paralysis
• Alcohol Abuse can make it difficult to absorb and store Vitamin B1

Question 16

Answer 16

Question 17

Answer 17

Question 18

Answer 18

Question 19

Electron Transport Chain

1. NADH transfers its electrons (x2) via___________________to flavin mononucleotide (FMN)
2. FMN passes the electrons to ______ via an iron-sulfur complex (____). Energy generated is used to pump protons into the intermembrane space
3. Coenzyme Q passes electrons to __________via cytochrome B and cytochrome C1. Electrons from FADH2 enter the ETC at ___________ (Why less energy than NADH?)
4. Cytochrome C passes electrons to __________ containing cytochrome aa3 complex which ultimately transfers the electrons to oxygen, reducing it to water. ________________ this final step of the ETC.

Answer 19

Electron Transport Chain

1. NADH transfers its electrons (x2) via NADH dehydrogenase complex (complex I) to flavin mononucleotide (FMN)
2. FMN passes the electrons to coenzyme Q** via an iron-sulfur complex (**Fe-S). Energy generated is used to pump protons into the intermembrane space
3. Coenzyme Q passes electrons to cytochrome C** via cytochrome B and cytochrome C1. Electrons from FADH2 enter the ETC at **complex II (energy generated less as Complex I is bypassed and Complex II does not pump protons into inter-membrane space.)
4. Cytochrome C passes electrons to complex IV** containing cytochrome aa3 complex which ultimately transfers the electrons to oxygen, reducing it to water. **Cytochrome oxidase catalyzes this final step of the ETC.

Question 20

The production of ATP is coupled to the transfer of electrons to oxygen through the electron transfer chain – hence the name: ___________________

Answer 20

The production of ATP is coupled to the transfer of electrons to oxygen through the electron transfer chain – hence the name oxidative phosphorylation

Question 21

The flow of protons through the _____________ (moving down their concentration gradient) generates the energy required to synthesize ATP

• It takes approximately ___protons to synthesize one ATP
• Each molecule of NADH results in ____ protons being pumped into intermembrane space
• FADH2 enters ETC at complex II and therefore only contributes ____ protons to intermembrane space

Answer 21

The flow of protons through the ATP Synthase pump (moving down their concentration gradient) generates the energy required to synthesize ATP

• It takes approximately 4 protons to synthesize one ATP
• Each molecule of NADH results in 10 protons being pumped into intermembrane space
• FADH2 enters ETC at complex II and therefore only contributes 6 protons to intermembrane space

Question 22

By what mechanism does the fish poison Rotenone inhibit the ETC?

Answer 22

Rotenone – fish poison that complexes with complex I

Question 23

What caused the diet drug Dinitrophenol to be so deadly?

Answer 23

Dinitrophenol: (Deadly Diet Drug) ionophores that allow protons from the cytosol to re-enter the mitochondrial matrix without going through the pore in the ATP synthase complex.

• This results in an ‘uncoupling’ of ATP synthesis from the electron transport chain
• ATP production decreases as the proton gradient across the inner membrane is dissipated
• Generation of ATP reduces = signals to cell that it requires more energy = rate of ETC increases and oxygen consumption increases

Question 24

How do Cyanide and carbon monoxide inhibit the Electron Transport Chain?

Answer 24

Cyanide and carbon monoxide** combine with cytochrome oxidase (**complex IV) and block the transfer of electrons to oxygen resulting in shutting down of the ETC.