Energy Metabolism 3 Flashcards
Chemiosmotic Theory: Proton gradient that drives ATP synthesis
- electron transfer from NADH to proteins in the inner mitochondrial membrane leads to a change in proton concentration on each side of the membrane. Energy is stored ion the transmembrane potential.
- principles
1. ATP is synthesised enzymatically by ATP synthase embedded in mitochondrial inner membrane
2. Energy needed to synthesise ATP is collected from a transmembrane potential, in this case a gradient of protons across the inner membrane
3. The gradient of protons is generated by redox reactions during transfer of electrons from NADH to molecular O2
Overview of movement through complexes
Coupling NADH oxidation to ATP synthesis is achieved by passing electrons through 4 protein complexes of electron transport chain.
Electrons removed from metabolic intermediates during oxidation reactions (NAD+, FAD) are shuttle to oxygen through electron carries.
These protein complexes contain redox centres with progressively greater affinities for electrons.
Path of electrons from different sources to ubiquinone
Carried by NADH, FADH
Electrons from different sources flow through ubiquinone (coenzyme Q) which is a small lipid soluble carrier
- electrons pass through series of membrane bound carriers.
Complex reduction requires two electrons and two proteins
All proteins in ETC act as scaffolding to hold flavin mononucleotide (FMN), iron sulphur centres and heme groups through which electrons pass.
NADH must release 2e to complex 1 which pass to coenzyme Q
Complex 1
- large protein complex
- contain 1FMN
- contains 6-7 FE-S clusters
- as e pass through this complex, four proteins are pumped from the matrix into the inter membrane space
- transports e from NADH to FMN to Hq
Complex 3
Accepts e from Hq and passes on to cytochrome c with transport of proteins from the matrix to the inter membrane space.
Cytochrome C moves to complex 4.
Qh2 is oxidised to Q
Complex 4
Catalyses reduction of oxygen to water
E flows from cytochrome c through copper to heme molecules and then to oxygen
4 e pass through complex when O2 converted to H2O
4 protons pumped from matrix into intermembrane space
ATP synthase
Contains two functional units:
- F0 (water insoluble transmembrane proton channel)
- F1 (water soluble peripheral membrane protein)
Inner mitochondrial membrane is studded with ATP synthase molecules
F1 connected to F0 by proteins talk
F0 subunit
- composed of subunits a, b and c
- subunit c is small, hydrophobic polypeptide composed of two transmembrane helices.
- form circle in the membrane
DccP binds to one of the subunits of the F0 complex and inhibits proton transport.
Inhibition of H+ flow from the intermembrane space back into matrix blocks ATP synthesis
F1 component
Beta subunit catalyses ATP synthesis
Gamma subunit spins
Beta subunit binds to ADP, conformational change, releases ATP
Amino acid sequence of beta Subunits are the same but different conformational change
The two beta subunits of F0 dissociate with beta subunit of F1
Uncoupling oxidative phosphorylation
- normally electron transport and ATP synthesis are tightly couple
- compounds such as dinitrophenol (DNP) can uncouple these processes.
DNP binds proton on acidic side of membrane- diffuse through and release them on alkaline side. This dissipates the proton gradient
Therefore electron transport proceeds but no ATP synthesis
ATP exiting mitochondria
In mitochondrial matrix but mostly used in the cytosol for active transport, biosynthesis etc.
mitochondrial inner membrane is generally impermeable to charged molecules but has an ADP- ATP translocator
Catalyses the couple entry of ADP and exit of ATP into/ from matrix
ATP leaves matrix and ADP enters
Favoured direction because inside is negative, therefore ADP goes in and ATP out
