BIOL 201 Lecture Notes - Lecture 8: Intermembrane Space, Succinate Dehydrogenase, Cytochrome C Oxidase

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7 Jun 2018
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Glucose has been converted into CO2, NADH, and a few ATP
Oxidation of the reduced coenzymes (10 NADH and 2 FADH2) has a total ΔG°′ of 613 kcal/mol,
free energy present in the chemical bonds of glucose is 686 kcal/mol, thus about 90 percent is conserved in the reduced coenzymes.
We now need to somehow use the energy captured in electron carriers
There is also an alternative pathway converting fatty acids into acetyl CoA
Where were we?
Protons simultaneously get pumped across membrane
NADH enters at complex 1, which will be shuttled to subsequent complexes and
carriers until they encounter oxygen to produce water
the ΔG°′ for ATP synthesis is substantially less than coenzyme oxidation
This would waste large proportion of energy as heat
Solve problem by generating more efficient proton motive force
A one-to-one reaction involving oxidation of one coenzyme molecule and
synthesis of one ATP would be terribly inefficient
The electron transport chain converts NADH reduction into a proton gradient
Four large multiprotein complexes (complexes IIV) compose the electron-
transport chain in the inner mitochondrial membrane that is responsible for the
generation of proton motive force
Each complex contains several prosthetic groups that participate
in the process of moving electrons from donor molecules to
acceptor molecules in coupled oxidation-reduction reactions
Electrons pass into outer orbitals of iron ion and can be quickly
transferred to orbitals of another
Most common iron cluster = heme group, as well as iron-sulfer clusters
Iron clusters and other “prosthetic groups” pass the electrons “downhill”
Reduction Potential: Readiness to gain an electron (Arbitrary zero point!)
If reduction potential of next iron cluster is higher, it will take the electron from
the previous one
Arbitrary 0 is relative to basic H2reaction
Reduction potential gets less negative (increases) as it flows through complex I,
simultaneously liberating free energy w/ -ΔG
The “reduction potential” of each electron carrier increases down the chain
CoQ can accept a single electron to form a semiquinone, a charged
free radical denoted by CoQ
Addition of a second electron and two protons (thus a total of two
hydrogen atoms) forms dihydroubiquinone (CoQH2), the fully
reduced form.
Reduced form = CoQH2
Encephalomyopathy
severe infantile multisystemic disease
cerebellar ataxia
isolated myopathy
nephrotic syndrome
Ubiquinone deficiencies cause disease, Phenotypes include disease that
effects muscle and neurons (highly energy dependent) :
Electrons are first passed to ubiquinone (CoQ), a lipid-like carrier
lipid like structure allows motion through plasma membrane
Matrix domain is where electron flow occurs, whereas proton
translocation occurs in membrane bound domain through 4 proton
channels
Protons are flowing against both concentration gradient and electrical
gradient
In Complex I, electron transfer and proton translocation are physically
separated
If you just punch a hole - protons will flow in the wrong direction
One way doors are impossible at the molecular level-would violate
second law of thermodynamics
Require simultaneous opening of 4 gates at once
How in CoQ reduction coupled to H+ movement? How do you construct a
gated proton channel?
Requires residue that "grabs" proton and then release it on other side
Ka = acid dissociation constant, “Affinity for protons”, pKa = pH at which
protein is at 50/50 protonated/deprotonated state
Proton translocation channels have residues with a regulated pKa
CoQH2 transfers the electrons to Complex III by diffusing through the membrane
Lysine residues in Complex I bind and release protons in response to CoQ reduction
Lecture 8: the Electron Transport Chain
January 29, 2018
9:44 AM
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Document Summary

Glucose has been converted into co2, nadh, and a few atp. We now need to somehow use the energy captured in electron carriers. There is also an alternative pathway converting fatty acids into acetyl coa. The electron transport chain converts nadh reduction into a proton gradient. Nadh enters at complex 1, which will be shuttled to subsequent complexes and carriers until they encounter oxygen to produce water. A one-to-one reaction involving oxidation of one coenzyme molecule and synthesis of one atp would be terribly inefficient the g for atp s(cid:455)(cid:374)thesis is su(cid:271)sta(cid:374)tiall(cid:455) less tha(cid:374) (cid:272)oe(cid:374)z(cid:455)(cid:373)e o(cid:454)idatio(cid:374) This would waste large proportion of energy as heat. Solve problem by generating more efficient proton motive force. Iro(cid:374) clusters a(cid:374)d other (cid:862)prosthetic groups(cid:863) pass the electro(cid:374)s (cid:862)dow(cid:374)hill(cid:863) Four large multiprotein complexes (complexes i iv) compose the electron- transport chain in the inner mitochondrial membrane that is responsible for the generation of proton motive force.

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