4D- Oxidative Phosphorylation and Mitochondrial Function

Question 1

What is the general mechanism of reoxidation of NADH and FADH2 by the electron transport system results in ATP synthesis?

Answer 1

c. In the electron transport chain, electrons are donated by NADH (complex I) or FADH2 coenzyme Q  complex III  cytochrome c  complex IV.
d. At complex 4 the electrons are used in the reaction ½ O2 + 2H+  H2O
e. As NADH + H+ and FADH2 donate their electrons, protons are pumped across the membrane into the intermembrane space. This generates a big electrical potential by a hydrogen gradient across the membrane. Complex V, AKA ATP synthase, utilizes this gradient by allowing protons to pass though it, converting the electrical gradient as energy for the reaction ADP + Pi  ATP

Question 2

What is significant of complex I?

Answer 2

i. NADH passes 2 electrons and 2 protons to FMN, which becomes FMNH2. This passes the electrons, 1 at a time, to Fe3+, which becomes Fe2+.
ii. Protons are released on the other side of the membrane

Question 3

What is significant of coenzyme Q?

Answer 3

i. The Fe2+ passes their electrons to ubiquinone (CoQ), which acquires a total of 2 electrons and 2 more matrix protons.

Question 4

What is significant of complex II?

Answer 4

i. Acquires protons and electrons from FADH2  FAD+
ii. FADH2 gives its electrons to Fe3+, and then Fe2+ gives its electrons to ubiquinone

Question 5

What is significant of cytochrome c?

Answer 5

i. CoQ passes the electrons onto site III heme and protons to outside of membrane
ii. It donates the electrons from heme of III to cytochrome c

Question 6

What is significant of Complex IV?

Answer 6

i. This site accepts electrons from Cyt c and then passes them to O2

Question 7

What is significant of complex V?

Answer 7

i. This is the ATP synthase portion.
ii. The overall reaction sequence is: ATP synthase + ADP + Pi → ATP Synthase + ATP
iii. Energy is often released in the form of H+, moving down an electrochemical gradient from the inter-membrane space into the matrix in mitochondria.

Question 8

Why do we require more O2 when our body creates more ADP?

Answer 8

As our muscles (or other tissues) work hard –> ADP levels rise –> proton influx increases –> electrochemical gradient decreases –> increased proton pumping –> increased O2 consumption

Question 9

What is uncoupling?

Answer 9

when protons leak back into the maritx without going through the ATP synthase

they dissipate the electrochemical gradient across the emmbrane without generating ATP

Question 10

What are chemical uncouplers?

Answer 10

lipid-soluble compounds that rapidly transport protons from the innter mitochondrial membrane to the matrix side

this dissipates the chemical potential gradient

eventally, mitochrondial integrity and function are lost.

Question 11

What are UCP’s and what do they do in thermogenesis?

Answer 11

uncoupling proteins (UCP’s) form channels through the inner mitochronial membrane and are assocated with heat production in brown adipose tissue

in response to cold, sympathetics release norepinephrine which stimulates UCP1 in brown fat to uncouple and generate heat

Question 12

What site does barbituates inhibit?

Answer 12

Complex I

Question 13

What site does CN inhibit?

Answer 13

Complex IV (cytochrome oxidase)

Question 14

How are mitochrondrial diseases inherited?

Answer 14

through maternal inheritance

mitochondrial DNA is inherited ONLY from the mother

Question 15

How does molecules such as adenine nucleotides and ions get across the mitochondrial membrane?

Answer 15

adenine nucleotides get across through a molecule known as ANT (adenine nucleotide translocase). this exchanges ATP out of the mito and takes ADP into the mito

ions use symporters or exchangers for entry/exit of mitochrondrium

Question 16

What happens when mitochondrial permeability transition pore opens?

Answer 16

protons flood in, mitochrondium swells and becomes irreversibly damaged –> cell lysis and death