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• Proton path through the membrane: Each proton enters cytosolic
half-channel, follows a complete rotaion of c ring, and exit through
the other half-channel into the matrix.
Many shuttles allow movement across the mitochondrial
membranes
Electrons from cytosolic NADH enter mitochondria by shuttles
•Glycerol 3-phosphate shuttle: e from NADH can enter mitochondrial e
transport chain by being used to reduce dihydroxyacetone phosphate to
glycerol 3-phosphate. Glycerol 3-phosphate is reoxidized by e transfer to FAD
in membrane-bound glycerol 3-phosphate dehydrogenase. Subsequent e
transfer to Q to form QH2 allows e to enter e transport chain.
•1.5 rather than 2.5 ATP are formed when cytosolic NADH transported by the
glycerol phosphate shuttle is oxidized by the respiratory chain.
The Entry of ATP into Mitochondria is Coupled to the Exit of
ATP by the ATP-ADP Translocase
Mitochondrial ATP-ADP translocase: Translocase catalyzes the coupled entry of
ADP and exit of ATP from matrix. The reaction cycle is driven by membrane
potential. The actual conformational change corresponding to eversion of binding
site could be quite small.
• ATP-ADP translocase: Adenine nucleotide carrier.
• ADP enters the mitochondrial matrix only if ATP exits, and vice versa.
• In the presence of a positive membrane potential, the rate of binding-site
eversion from the matrix to the cytosolic side is more rapid for ATP than for
ADP because ATP has one more negative charge.
• The membrane potential is decreased by the exchange of ATP for ADP, which
results in a net transfer of one negative charge out of the matrix.
The regulation of cellular respiration is converted primarily
by the need for ATP
The Complete Oxidation of Glucose Yields About 30 ATP
About 30 ATP are formed when glucose is completely oxidized to CO2.
The Rate of Oxidative Phosphorylation is Determined by
the Need for ATP
• electron transport tightly coupled to phosphorylation: Electrons do not
usually flow through the electron transport chain to O2 unless ADP is
simultaneously phosphorylated to ATP.
• Level of ADP: the most important factor to determine rate of oxidative
phosphorylation
•Respiratory control: e are tranferred to O2 only if ADP is concomitantly
phosphorylated to ATP.
Oxidative phosphorylation can be inhibited at many stages
• 1) e-transporter inhibitor
•Rotenone/ Amytal.
• Antimycin.
•Cyanide/ azide/ carbon monoxide
•2) ATP synthase inhibitor
•ATP synthase can be inhibited by
oligomycin and DCCD.
•3) uncoupler: This tight coupling of electron transport and phosphorylation in
mitochondria can be disrupted by 2,4-dinitrophenol and certain other acidic
aromatic compounds. These substances carry protons across the inner
mitochondrial membrane.
• 4) ATP export: ATP-ADP translocase inhibited by atractyloside, bongkrekic
acid
Regulated uncoupling leads to the generation of heat
• The uncoupling of oxidative phosphorylation is a means of generating
heat to maintain body temperature in hibernating animals, in some newborn
animals, and in mammals adapted to cold.
• brown adipose tissue: specialized for nonshivering thermogenesis
• UCP-1 (thermogenin): uncoupling protein in inner mitochondrial
membrane
• UCP-1 generates heat by short-circuiting the mitochondrial proton battery.
• action of UCP: UCP-1 generates heat by permitting the influx of protons
into the mitochondria without synthesis of ATP.
Mitochondria play a key role in apoptosis
• Programmed cell death/ apoptosis
• activation of caspase: destroy of cell structure
• degradation of protein that inhibits an enzyme that destroys DNA
Power Transmission by Proton Gradients: A Central Motif
of Bioenergetics
* Proton gradients are a central interconvertible currency of free energy in
biological systems.