Lecture 33: Oxidative Phosphorylation: ATP synthesis and regulation Flashcards Preview

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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




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



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 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?



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