Lecture 33: Oxidative Phosphorylation: ATP synthesis and regulation Flashcards
What are the two main parts of ATP synthase?
F0-intergral transmembrane part
F1-knobby parts that sticks into the mitochondrial matrix
ATP synthase function parts
Rotor
Stator
Rotor
comprised of:
- c subunits (10 to 14)
- E subunit
- Y subunit
all of these subunits rotate together when protons move one at a time from the P side to the N side
- always turns in the same direction
- is energized by the proton-motive force at each B subunit
- wholve revolution of rotor to produce One ATP
Stator
Comprised of:
- b2 subunits
- S subunit
- hexamer of a-b-subunits
entire complex is fixed in the membrane and cannot rotate with the rotor
How does ATP synthase work?
The c subunit complex rotates in the membrane as H+s move from the P to the N side of the inner membrane
Y subunit works by
y subunit of the rotor rotates with the c subunits
- sticks into the center of the hexameter complex made up of the a-b-pairs
- assymetric and as induces a conformational change in the B-conformatoion as it rotates past a B subunit of each a-B pair
Types of conformations from ATP symthase
Open
loose
tight
Open conformation
dissociation of ATP and allow association of ADP and Pi
Loose conformation
ADP and Pi bound and reaction
Tight conformation
ATP bound
how many protons are used for each ATP synthesized?
3
Issues concerning transport of metabolites though the mitochondrion
- none of the molecules ADP, Pi, or ATP are freely diffusing through the inner membrane- NEEDS TO BE A WAY TO GET ADP AND Pi into the matrix and ATP out
2) Two NADH molecules are made in the cytoplasm from each glucose during glycolysis. NADH cannot freely diffuse through the mmembrane SO NEEDS A WAY TO GET NADH INTO THE MATRIX
Solution to get ADP and Pi into the matrix
Adenine nucleotide transporter
Pi Transporter
BOTH cost the cell the equivalent of one proton that would otherwisee would be available for ATP synthesis
Adenine Nucleotide transporter
antiport translocase
- moves ADP^3- into the matrix and ATP^4- out of the matrix
- exchange is drive by the higher negative charge in the matrix thane the inter membrane space
Pi Transporter
Pi and H+ are moved together
- doesn’t change the amount of charge
- does change pH
NADH movement into the matrix
Malate-aspartate shuttle is used
malate-aspartate shuttle
two antiports are involved:
- malate/a-ketogluterate antiport
- aspartate/glutamate antiport
-6 total reacotns
What does the malate-aspartate shuttle result in?
the moment of one NADH equivalent from the cytoplasm into the matrix
What are the two key reactions of the malate-aspartate shuttle
- oxidation of malate to oxaloacetate in matrix
- reduction of oxaloacetate to malate in cytoplasm
Glycerol phospahte shuttle
Getting reducing equivalents into the matrix
- NADH is oxidized by dihydroyaceton phosphate to produce glycerol 3-phosphate in inter-membrane space
- Glycerol 3-phosphate on the inner membrane is oxidized and produces FADH2
- FADH2 in the membrane is oxidized to produce FADH2 in the membrane
- FADH2 feeds complex III
Hypoxia dangers
low O2 concentration and pressure
1) respiration cannot occur because of lo2 pO2 and cells suffer ATP deficiency
2) without high enough O2 in complex III, there is accumulation of free radicals
- radical FADH- reacts with O2 to create a reactive oxygen species-radical O2- is extremely damaging to proteins and nucleic acids
Reactive oxygens species (ROS)
radicals OH and O2
Mechanisms to avoid Hypoxia
1) Glycolysis increase, but entry of pyruvate into the TCA cycle is inhibited, and ATP is produced anaerobically
2) Reduction in the citric acid cycle reduces electron flow through oxidative phosphorylation
3) A more effective Cox 4-2 subunit (part of complex IV) is mobilized
