Charging The Cellular Batteries Flashcards
What is the ‘ATP battery’ charged with?
- Catabolism of organic carbon substrates
- photosynthesis
What does the ‘ATP battery’ discharge?
free energy coupled to thermodynamically unfavourable reactions for biosynthesis of cellular components
Why is ATP useful as an energy carrier?
Interconversion between ATP and ADP + Pi has an unusually high Keq
Keq
- Equilibrium constant
- concentration of products / concentration of reactants
How much ATP will there be at equilibrium?
Vanishingly small amounts
At what concentration is ATP maintained in a cell, relative to ADP
~3 fold greater
What are the typical concentration of ADP, ATP and Pi in a cell?
ADP = 1mM
ATP = 3mM
Pi = 10mM
How far is the ATP reaction displaced from equilibrium?
30,000 fold
Properties of ATP
- thermodynamically unstable
- kinetically stable
- middling relative Gibbs free energy release on phosphoester hydrolysis (compared to other phosphate compound)
Why is the middling free energy of ATP hydrolysis important?
Unfavourable reverse reaction (condensation of ADP and Pi to form ATP) can be found oven by coupling to other phosphate compound hydrolysis
What are the two mechanisms to charge the ATP battery
- Substrate-level phosphorylation
- Oxidative phosphorylation
Substrate-level phosphorylation
- metabolic reaction for ATP formation by direct transfer of PO3 to ADP, from another phosphorylated compound
- Phosphate is passed from one substrate to another
- requires large free energy coupling reactions, because of unfavourable synthesis
PO3
Phosphoryl group
NAD+
Nicotinamide adenine dinucleotide
NADH formation equation
NAD+ + H+ + 2e- -> NADH
Describe substrate-level phosphorylation
1) hexose sugar formed
2) double phosphorylated triose formed
3) phosphoryl transfer from triose to ADP
Why do you need fermentation in the absence of oxygen?
To maintain glycolysis, through NAD+ electron acceptor regeneration
Where is NAD+ regenerated?
As a byproduct of the transition of acetaldehyde to ethanol
Describe the electron transport chain
- embedded into cell membrane
- 4 separate protein complices
- contains electron carriers
- complices I, III and IV span the membrane
Give an example of an electron carrier
Cytochrome c
What supplies the electrons to the electron transport chain
The tricarboxylic acid cycle
What is the tricarboxylic acid cycle
An oxidative metabolic cycle
Describe the process of electron transport
- each ETC complex is reduced the oxidised as it receives and passes on an electron pair to the proceeding complex (reduction-oxidative cycle)
- oxygen is the terminal electron acceptor
Describe oxygen reduction to water as the terminal electron acceptor
1/2O2 + 2e- + 2H+ <-> H2O
Describe the action of complices I, III and IV
- on each reduction-oxidation cycle, they pump a proton from the cytoplasm across the membrane
- creates a proton gradient
What does the proton gradient in oxidative phosphorylation represent?
- a source of potential energy (chemical and charge gradient)
- a proton motive force
What does the proton motive force do?
Drives ATP synthesis via ATP synthase protein complex
Why is oxidative phosphorylation called that?
Because it relies on oxidative metabolism, not oxygen involvement
Describe the composition of protein complices
- Flavin mononucleotide
- Fe-S clusters
- Ubiquinone
From where is flavin derived
Vitamin B2
Ubiquinone aka
Coenzyme Q10
Describe e- transport and H+ pumping by complex I
- chain of redox centres (mostly Fe-S) allow electron jumping
- oxidised Ubiquinone binds to channel
- 2e- from NADH to ubiquinone releases much free energy
- drives a series of piston like conformational changes
- 4H+ channels open towards inside of cell
- protons enter connected water river running through centre of membrane arm
- conformational change pushes protons to the left; opens channels to the outside of the cell
- proton ejected
Describe electron jumping
Occurs over a precise position and distance
Describe the Ubiquinone channel
Tight
Redox active metals and organic compounds facilitate
Electron transfer
Haem
A tetrapyyrole ring with Fe atom in centre
As you go down the ETC
- electron carrier reduction potential increases (from -0.420V to + 0.031V)
- decreasing tendency to donate electrons
How does e- transport drive proton pumping?
- electron transport releases free energy
- drives conformational change in ETC complices - protons pumped from inside cell, across cell membrane, into periplasmic space
Carboxylic acids were most likely
The first molecules to spontaneously arise from CO2 and H2
Conditions required for carboxylic acid synthesis
- high temp (40-70)
- high pressure
- reduced redox-active metals (Fe, No£
ATP Synthase is a
- rotary motor
- subunit a provides a periplasmic space half channel and à cytosolic half channel
- subunit c ring and aspartic acid (conserved)
Summary of OP
- oxidative glycolysis metabolism and TCA cycle provide electrons from carbon substrates carried by NADH and FADH2
- electrons pass down ETC
- ETC reduction-oxidation cycles release free energy
- free energy coupled to proton pumping through respiratory complices
- electrochemical gradient powers ATP synthase rotary motor
- oxygen is reduced to water, as terminal electron acceptor
ETC
series of large membrane spanning protein complices connect by mobile electron carriers
Examples of mobile electron carriers
- ubiquinone (Q)
- cytochrome c
Advantages of proton gradients
- Flexible
- Efficient
Describe the flexibility of proton gradients
Energy sources (fuel) is irrelevant as long as electrons can be extracted and given to universal electron carriers for proton gradient generation for ATP Synthesis
Give an example of a universal electron carrier
NAD+
Substrate level phosphorylation is
- tied to a specific chemistry
- less flexible than oxidative phosphorylation
Describe the efficiency of proton gradients
Regeneration of NAD+ allows more energy to be extracted from carbon sources as they pass down ETC
What generates the cellular battery?
Displacement of ATP:ADP ratio from equilibrium
What is the cellular battery?
The chemical energy store
All chemical reactions tend towards
Equilibrium
What does it mean if something is kinetically unstable?
- Slow, needs catalysis
- means you can control its coupling
Pyruvate
Triose
Oxygen is an
Abundant, relatively available electron acceptor that is easy to reduce, and gives the benign product, water
Synthesis of CoA requires
Vitamin B5
Examples of carboxylic acids
- Fatty acids
- Amino acids
What are carboxylic acids the result of?
Spontaneous chemistry at the evolution of life
Carboxylic acids are
Conserved universally, in all branches of the evolutionary tree
Where do the conformational changes occur in the ATP synthase rotary motor?
In the head group
The C ring in the ATP synthase rotary motor is made up of
Multiple c subunits
What did the occurrence of oxygen in the atmosphere allow?
increased efficiency of fuel extraction