Biochemistry Part 7 Flashcards
What is produced from one glucose molecule through glycolysis, PDC, TCA cycle…?
10 NADH + 10 H+
2 FADH2
What is the essence of oxidative phosphorylation?
Electrons from NADH and FADH2 are used to reduce O2 to H2O
Their energy is used to pump protons from the mitochondrial matrix to the inter membrane space
- pH decreases in inter membrane space, increases in the matrix
Protons flow back across the membrane, following their concentration gradient
Energy of proton flow is used to phosphorylate ADP to ATP
How does NADH from the cytoplasm get in?
The glycerol-3-phosphate and malate-aspartate shuttles overcome this problem
Describe the malate-aspartate shuttle?
- NADH from glycolysis is used to generate malate from oxaloacetate in cytosol
- Malate transporters transfer malate to mitochondrial matrix
- Malate conversion to oxaloacetate in TCA cycle generates NADH in addition to malate that arises from fumarate
What is the electron transfer potential of NADH converted into in oxidative phosphorylation?
The phosphoryl transfer potential of ATP
How can phosphorylation transfer potential be measured?
The free energy change, delta G for the hydrolysis of ATP
How can the electron transfer potential measured?
The redox potential (or reduction potential) of a compound
What is the redox potential?
The measure of how readily a substance will donate an electron in comparison to H2
What does a negative Eo mean?
The reduced form of X has a lower affinity for electrons that H2
What is the standard free energy proportional to?
The change in standard redox potential and the number of electrons transferred
What are the two stages of oxidative phosphorylation?
Electron transport
ATP synthesis
Describe electron transport
Electrons flow from NADH and FADH2 to O2
Respiratory chain
Energy is used to pump H+ out of the mitochondrial matrix
Describe ATP synthesis
Electrochemical gradient of H+ across mitochondrial inner membrane
Energy stored in this gradient can be used to synthesis ATP
How many complexes are involved in electron transport in the respiratory chain?
Four multisubunit complexes
Located in inner mitochondrial matric
What is complex I and what happens here in the respiratory chain?
NADH-Q oxidoreductase
Electrons from NADH enter
What is complex II and what happens here in the respiratory chain?
Succinate-Q reductase
Electrons from FADH2 enter here
What is complex III in the respiratory chain?
Q-cytochrome C oxidoreductase
What is complex IV in the respiratory chain?
Cytochrome C oxidase
What are cytochromes?
Proteins which contain a haem group as a functional cofactor
What does the haem group do?
Contains an Fe(II) ion which can take up and release electrons
What is transfer of electrons through the respiratory chain coupled to?
Transport of H+ from the mitochondrial matrix to the inter membrane space
Which three respiratory chain complexes pump H_?
I, III, IV
What forms the electrochemical gradient in the inter membrane space and matrix?
More protons in the inter membrane space than in the matrix
How is the flow of protons regulated across the membrane?
Respiratory chain pumps protons into inter membrane space
Protons flow back though ATP synthase
Two separate proton pump systems
What is the other name for ATP synthase?
Mitochondrial ATPase
F1F0ATPase
Describe the F1 unit of ATP synthase?
Protrudes into the mitochondrial matrix
Describe the F0 unit of ATP synthase?
Hydrophobic complex in the inner membrane, contains the proton channel
What forms the stator?
a, b, alpha, beta, sigma subunits
What forms the rotor?
c, gamma and epsilon subunits
What turns the rotor?
Flow of protons
What leads to ATP synthesis?
Conformational change
What can oxidative phosphorylation by inhibited by?
Cyanide, azide and CO
- Inhibit transfer of electrons to O2
- no proton gradient can be formed
- no ATP can be synthesised
Describe non-shivering thermogenesis?
Maintains body temperature in hibernating animals and newborn, and cold adapted animals by short circuiting the mitochondrial battery
What is the uncoupling protein and where is it found?
UCP= thermogenic
Brown adipose tissue
What does UCP-1 require for activation?
Free fatty acids
What is DNP?
Artificial uncouples which acts as a protonophore in the inner membrane
- used as antiboesity drug
Where is UCP-3 expressed?
Skeletal muscle
What is uCP-3 involved in?
Skeletal muscle thermogenesis and limiting free radical production
What is the pharmacological target of UCP-3?
MDMA, ecstasy
How does MDMA cause death?
Sustained hyperthermia followed by skeletal muscle breakdown (rhabdomyolysis)
What is the P/O ratio?
Measurement of the coupling of ATP synthesis to electron transport
What does the number of molecules of inorganic phosphate incorporate into ATP per atom of oxygen used depend upon?
The substrate which is oxidised
How many ATP does one glucose molecule yield?
30 to 32
ATP yield from the complete oxidation of one glucose molecule
Depends on precise values for the P/O ratio
Depends on which shuttle is used for transporting cytoplasmic NADH into the mitochondrial matrix
