Oxidative Phosporylation/Electron Transport Chain

Question 1

Complex I

Answer 1

• NADH Dehydrogenase
• NADH:Q reductase
• NADH oxidized and e- carried to CoQ
• Q is reduced to QH2 and taken to Complex III
• 4H+

Question 2

Complex II

Answer 2

• Succinate Dehydrogenase
• Part of TCA cycle (Only one not in matrix)
• FADH2 donates e- to Q forming QH2
• QH2 goes to complex III and oxidized to Q
• Succinate converted to fumarate
• Pumps NO protons

Question 3

Complex III

Answer 3

• Cytochrome bc1
• Cytochrome c reductase
• Reduces cytochrome c
• cytochrome c takes e- to complex IV
• 4H+

Question 4

Complex IV

Answer 4

• Cytochrome oxidase
• Cytochrome aa3
• Cytochrome c enters and reduces O2 to H2O
• 2H+

Question 5

Complex V

Answer 5

• ATP Synthase
• F1F0 ATPase
• protons flow thru and spin the subunits to convert ADP to ATP
• Proton motive force: electrochemical potential driving protons into the cell thru ATPase
• 4 protons needed for 1 ATP (3 for formation and 1 for transport)
• Adenine nucleotide transporter exchanges ADP for ATP bringing ADP in & ATP out

Question 6

5 non-protein components

Answer 6

1. Flavin: FAD and FMN
2. Fe-S-4Fe, 2Fe (non-heme iron)
3. Quinone: CoQ10
4. Heme a, b, b
5. Copper: Cua and Cub

Question 7

Leber Hereditary Optic Neuropathy (LHON)

Answer 7

*Maternally inherited
*Acute, late onset, optic atrophy
*Sudden blindness in one eye followed by later loss of vision in the other eye
*Point mutation in mtDNA for complex I
-Affect e- transport from Complex I to CoQ
*heteroplasmy: mixed populations of mito w/in given cell: some have mutations some don’t
*High mutation rates b/c reactive e- damage by forming free radicals
Threshold effect: accumulation of mutations

Question 8

OXPHOS Diseases

Answer 8

• Mutations in mrDNA affecting tRNA or rRNA
• MERRF: myoclonic epilepsy and ragged red fiber disease
  
  • clumps of diseased mitochondria accumulate in the subsarcolemmal region of the muscle fiber
• MELAS: mitochondrial encephalomyopathy, lactic acidosis and strokelike episodes

Question 9

Inhibitors of Electron Transport

Answer 9

• NADH dehydrogenase blocked by rotenone and amytal
• cytochrome b blocked by antimycin A
• cytochrome a blocked by CN- N3- and CO

Question 10

Acceptor Control (ADP)

Answer 10

• Adding ADP caouses transient O2 consumption and ATP formation
• ADP concentration controls rate of O2 consumption

Question 11

Uncoupling

Answer 11

• Compound that uncouples oxidation from phosphorylation
• Ex. DNP
• Dissipates proton gradient
• Indefinite O2 consumption
• No ATP produced even w/ ADP present

Question 12

Brown Fat

Answer 12

• Natural uncoupler protein called thermogenin
• Used by infants to produce heat
• Under hormonal control (norepinephrine) to allow protons to cycle
• breakdown FA to make heat

Question 13

ATP Synthase Mechanism

Answer 13

• F0 is membrane bound proton conductance pore
• F1 is catalytic head w/ 3 alpha beta dimers connected to gamma subunit
• Protons flow thru and spin subunits causing gamma subunit to bump alpha/beta resulting in ATP
• Changes conformations of subunits: from loose to tight to open releasing ATP