OxPhos - Agbas

Question 1

membrane systems in mitochondria; features and permeability

Answer 1

outer - permeable to small molecules

inner - (internal ridges = cristae), respiratory chain, impermeable to small molecules (except O2, CO2, H2O, NH3)

Question 2

compartments in mitochondria, their pH, and what they used for

Answer 2

• intermembrane space (OxPhos in inner mitochondrial membrane) [LOW pH]
• matrix (site of most of TCA cycle and fatty acid oxidation) [ HIGH pH]

Question 3

mitochondria can’t stay alive by themselves but can divide and come together via..

Answer 3

divide = FISSION

come together = FUSION

Question 4

standard redox potential def., units, implication

Answer 4

measure of affinity of redox pair of electrons
unit: volt (V)
redox pair with lower E0’ has lower affinity for electrons; so gives it up easily to a redox pair with higher E0’

Question 5

species giving away the electron is the

Answer 5

reductant

Question 6

species receiving the electron is the

Answer 6

oxidant

Question 7

overproduction of RNS and ROS

Answer 7

damages induced on DNA, proteins, lipids (membran compromised)

Question 8

normal production of RNS and ROS

Answer 8

physiological signaling leading to Growth, hormone synthesis, inflammation

Question 9

OxPhos goals

Answer 9

• transfer electrons from NADH and FADH to O2
• establish proton gradient across inner mitochondrial membrane
• synthesize ATP

Question 10

CoQ transfers electrons

Answer 10

from Complex I and II to III

Question 11

boimarker for mitochondria function in disease process

Answer 11

Cyt-C
embedded in membrane on one side as a PERIPHERAL protein
so if membrane integrity compromised (e.g. RNS/ROS) - it gets release din the cytosol

Question 12

forms of electrons in ETC

Answer 12

electrons e-
hydride ions H-
Hydrogen atoms H+

Question 13

Complex I inhibited by

Answer 13

amytal
rotenone
myxothiazol
piericidin A

Question 14

complex II inhibited by

Answer 14

malonate

Question 15

complex III inhibited by

Answer 15

antimycin

Question 16

complex IV inhibited by

Answer 16

CO
Cyanide
H2S

Question 17

complex V inhibited by

Answer 17

Oligomycin

Question 18

if Complex I, IV affected, can lead to

Answer 18

• mitochondrial encephalopathy, lactic acidosis and stroke (MELAS)
• myclonic epilepsy and ragged-red fiber disease (MERRF)
• leigh syndrome
• hypertension and hypercholesterolemia
• diabetes with deafness

Question 19

complex I, III affected

Answer 19

leber hereditary optic neuropathy (LHON)

Question 20

complex III, IV affected

Answer 20

hypertrophic cardiomyopathy (exercise intolerance)

Question 21

if all complexes of ETC effected

Answer 21

kearns-sayre syndrome

- pearson syndrome

Question 22

2 factors constituting PMF to drive ATP synthesis by complex V

Answer 22

• pH gradient

- membrane potential

Question 23

chemiosmosis

Answer 23

oxidation of substrates is coupled to the phosphorylation of ADP

Question 24

uncouplers like 2,3 dinitrophenol (DNP) allow..

Answer 24

for the consumption of O2 without ADP!

normally O2 consumed only with ADP, excess Pi

Question 25

energy required by ATP synthase (complex V); inhibitors?

Answer 25

7. 3 kcal/ mol to form ATP from ADP + Pi | - oligomycin disrupts proton transport through the channel

Question 26

membrane damage by these can allow H+ to cross back into matrix

Answer 26

AraC | AZT

Question 27

proton carrier uncouplers

Answer 27

DNP | Aspirin

Question 28

heat generation uncouplning involves

Answer 28

thermogenin (UCP-1) | used by hibernating animals

Question 29

electron transfer is coupled to proton gradient in

Answer 29

oxidative phosphorylation

Question 30

what happens if proton gradient is disrupted?

Answer 30

P-DP uncomples from electron transfer - protons reenter mitochondrial matrix from intermembrane space - TCA cycle and electron transfer to O2 are accelerated - ATP synthase is inhibited Heat generation!

Question 31

OxPhos regulation is sensitive to

Answer 31

O2 | ATP/ADP ratio

Question 32

high [ATP/ADP]

Answer 32

``` inhibits ATP synthase increases H+ gradient decreases electorn transpot and H+ pumping slows down TCA cycle decreases glycolysis decreases ATP ```

Question 33

low [ATP/ADP]

Answer 33

``` activates ATP synthase decreases H+ gradient increases elecron transport and H+ pumping accelerates TCA cycle increases glycolysis INCEASES ATP ```

Question 34

SOD in intermembrane space

Answer 34

SOD1 (usually cytosolic) | SOD2 is in matrix!!

Question 35

ATP synthasome

Answer 35

ATP-ADP translocase Phosphate carrier ATP synthase

Question 36

malate-aspartate shuttle - where does it operate and what does it do

Answer 36

operates in heart, liver and kidney | helps NADH enter ETC at complex I

Question 37

glycerophosphate shuttle

Answer 37

operates in skeletal muscle and brain | helps FADH2 donate its electron to the ETC at CoQ

Question 38

one complex protons MUST go through to generate ATP, or otherwise excess H+ will be used for heat generation

Answer 38

complex IV

Question 39

redox couples involve

Answer 39

metals only e- transfer COUPLES have FRICTION - METAL

Question 40

redox pairs involve

Answer 40

NADH, FADH2 | e- AND H+ transfer