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Bioenergetics oxidative phosphorylation
Ch.6 Bioenergetics and oxidative phosphorylation
The energy is constant
E=change in internal energy
q=heat absorbed by system
w=work done by system
ex. ice water transition
G=change in free energy
H=change in enthalpy
S=change in entropy
: rubber band
rxn does not serve as an energy source in cells
ADP is indirectly used as energy source.
Adenylate kinase rxn
Creatine phosphate + ATP=creatine +ADP
If intake more creatine=problem with kidney filtration and votiming
Reservoir of high energy phosphate in muscle cells
Citric acid cycle produces
Nadh + H and FADH
Electron transport system responsible for
re-oxidation of nadh+h and FADH by o
oxidative phosphorylation process
ATP synthesized as electrons pass from NADH+H and FADH
major site for ATP production in tissue
ADP level controls the rate
02 depends on availability of ADP
electron carriers in electron transport system
iron in the heme in either state (Fe
Chemiosmotic Theory (Proton-motive force)
In electron transport H goes out of mitochondria, sets up a gradient with H
greater conc outside the inner membrane
The force increases synthesis of ATP by ATP synthase
H ions pass back into the matrix
e pair pass from FADH to O2 generates 2.5atp
e pair bypass complex I from FADH to O
slide 22: Inhibitor of atp synthase
1. amobarbital (amytal, barbituate), and rotenone
: blocks e transport, in Complex I
2. Antimycin (antibiotic)
: blocks e transport, in complex III
: blacks atp synthase in complex V
ATP made from ADP+P, by a proton gradient across the inner mitochondrial membrane
slide 16 Respiratory complexes
electron passes through complexes I,III,IV
ions are "pumped" across inner mitochon-memb into intermembrane space.
1. mitochondrial matrix
conc. in intermembrane space increases
2. Proton motive force as a result of
A. difference of PH
B. Difference of electrical potential between intermem-space and mito-matrix.
38 atp generated from glucose to CO
A. 1nadh-> 3atp
B. 1fadh-> 2atp
ADP controls the rate of oxidative phospho.
LOW adp (low ATP)
decrease flow of e
decrease 02 consumption
HIGH adp (high ATP)
increase flow of e
increase 02 consumption
pills taken for high cholesterol
Increased chol.=increased CoQ10 (statin) given= increased muscle pain.
inhibit electron transport
inhibit oxidative phospho. if coupled to electron transport
A. carbon monoxide
They are poisons because they compete with O
for binding to cytochrome oxidase of the ETC.
cyanide gas production
from bonding of C,H, and N during burning of synthetic materials.
in all cars, garage, dumpster, house fires.
prevents body from using O
no matter how high of oxygen you get.
cyanide exposure, s&s
ingested or absorbed
similar to CO
***Cyanide (Lilly) kit has
amyl nitrite (inhaler)
sodium thiosulfate (IV)
: convert hemoglobin to methemoglobin
: removes cyanide from cytochrome oxidase from cell allowing cell resp.
: bonds to freed cyanide making thiocyanate then renally excreted
side effects of lilly kit
: cause hypotension
: prevents 02 transport
bad following smoke inhalation
***Cyanokit: low side effects
Contains: Hydroxocabalmin binds with
****cyanide to create B12 (cyanocobalamin)
non toxic - excreted by kidneys
2vials of hydrocab 2.5gm
5 grams infused over 15min
: hypotension, lactic acidosis >10, high venous 02 SKIP
cause a "proton leak" allowing prot to re-enter mito. matrix without capturing En- ATP
in other words
: they carry H
across mit. mem. without going through comlex 5. this short circuits proton gradient and uncoup e flow.
E that would be used to make ATP is dissipated as heat
***in class notes***
Uncouple atp synthase from ETC
lower proton gradient
atp synthase (complex 5) cant make ATP
lack of energy, inc. ETC, which Inc. 02
the resulting energy is lost as heat
: will lower atp prod. and slow down the ETC
DNP collapses the H gradient across the membrane
found in brown fat
a med that was used for weight loss, and caused blindess (retina has oxidative metabolism)
uncoupler protein: thermogenin
mito. of brown fat
allows proton pass through inner membrane without synth. ATP
energy given off as heat to maintain body temp (in newborns)
hormone stimulates heat production
Mito. transport system
ATP-ADP translocase in inner mitoch. memb. carries coupled exchange of atp & adp
outer membrane is
, Inner memb. is not
shuttle transport e from cytosolic nadh into mito.
shuttle permits regeneration of cytosolic NAD which is necessary for glycolysis to continue
slide 46: Glycerol phosphate
shuttle uses cytosolic NADH to reduce dihydroxyactone phosph. to glyc 3 phosph.
transfers e to fAD in inner mito. memb.
2cytosolic nadh = 4atp
: muscle & brain
: unidirectional and costs 1 ATP
2 nadh formed
: 2x1.5= 3atp
shuttle uses cytosolic nadh to reduce oxaloacetate to malate
enters mito. by an antiporter
2nadh = 6 atp
: liver, kidney, heart
: bidirectional, cost no atp.
pyruvate dehydrogenase atp yield
2 nadh formed = 5 atp
atp yield from glucose oxidation
Citric acid cycle
2 turns of cycle required
: 30 or 32ATP depending on which shuttle
affect e transport and atp synthesis
mutations in mit. DNA (mtDNA)
mito. in the zygote come from ovum; they have
mothers transmit disease to children
males dont transmit because tail of sperm (contains the mito.) falls off during fertilization
mtDNA proteins are associated with e transport and atp synthesis
tissues with high o2 demand are most effected by mito. dysfunction.
Leber's hereditary optic neuropathy
loss of vision and blindness due to
degeneration of optic nerve
defect in nadh dehydrogenase (complex I)
paralysis of ocular muscle (ophthalmoplegia)
ragged red fibers
abnormal mito. that stain red
6.1 pt. with large mitochondria with packed cristae. high basal ATPase activity. oxidation and phosphorylation uncoupled
pt has hypermetabolism and high core temp.
6.2 why and how malate aspartate shuttle moves nadh reducing cytosol to mito. matrix.
there is no transport for nadh in inner mito. memb.
nadh can be oxized to nad by cytoplasmic isozyme malate dehyd. as oxaloacetate is reduced to malate
malate is transported across inner membrane, mito. isozyme of malate dehydrogenase oxidizes to oxaloacetate as mito. nad is reduced to nadH
The nadh can be oxidized by complex I of ETC generating 3 atp through the coupled process of resp. and oxidative phosphor.
6.3 CO binds/inhibits complex IV of ETC. what effect should respiratory inhibitor have on oxidative phosphor.
inhibition of ETC by resp. inhibitors such as CO result in inability to maintain proton gradient
oxidative phosphor. is therefor inhibited