Lecture 20 PMF

7/24/2019 Lecture 20 PMF

http://slidepdf.com/reader/full/lecture-20-pmf 1/26

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Discovery of Oxidative Phosphorylation and the

Mechanism of ATP SynthaseDr. Peter Mitchell was awarded the 1978Nobel Prize in Chemistry for formulating

the chemiosmotic hypothesis that

describes the process by which oxidative

phosphorylation occurs.

In 1997, Drs. Paul Boyer and John

Walker jointly received the NobelPrize in Chemistry for elucidating

the mechanism of ATP Synthase.

Boyer Walker

Mitchell

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NADH + 1/2 O2 + H+ => H2O + NAD+ !G = - 53 kcal/mol

ADP + Pi + H+ => ATP + H2O !G = + 7.3 kcal/mol

The pH in the inter-membrane space is 1.4 units lower than in the matrix

The potential over the inter-membrane due to the charge separation is 0.14 V

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Reaction Catalyzed by ATP Synthase

• ATP is synthesized through the condensation of ADP and Pi, the reverse of hyolysis

Mg2+ complexes of ADP and ATP are the actual substrates (similar to NMP kinase).

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Matrix

Intermembrane

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R #./7.&A41./< .7

L = Loose State: Binds ADP +

Pi tightly

T = Tight State: Binds ATP

more tightly than ADP + Pi; this

favors ATP formation

O = Open State: Binds ADP or

ATP loosely, permitting their

dissociation

subunits - Can bind ATP,but do not participate

chemically in catalysis.

subunit - Rotation

interconverts the T, L, and O

states of the 3 #

subunits.

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The counterclockwise

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subunit leads to the

interconversion of the T,L, and O states of the #

subunits, catalyzing the

formation and release of

ATP from the enzyme.

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C-ring (rotor)

Matrix

A-protein (stator)Hydrophilic pockets

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Entry of ADP and Exit of ATP Is Tightly Controlled

by the ATP-ADP Translocase

ATP and ADP are membrane impermeable - ATP generated in the mitochondrialmatrix cannot diffuse into the cytoplasm.

The ATP-ADP translocase catalyzes the exchange of ADP from the cytoplasm intothe mitochondrial matrix and also transfers a molecule of ATP from the

mitochondrion into the cytoplasm.

K"?%=41./ .7 RGI-,.< B: >$< /""5

• The synthesis of ATP from ADP and Pi regulates the flow of electrons throughthe electron transport chain.

• The availability of NAD+ and FAD regulate the rate of the TCA cycle. 22

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Uncoupled e – transport:Energy is released, but no

ATP is generated

DNP is in some Herbicides

and fungicides

Inhibition of oxidative phosphorylation

Thermogenin

An uncoupler

Other Transporters of

Mitochondria

Summary

• Oxidative Phosphorylation occurs in mitochondria

• Ox-Phos depends on electron transfer

The respiratory chain consists of four complexes:three are proton pumps

• A proton gradient powers the synthesis of ATP

• Shuttles allow movement across membranes

• Ox-Phos is regulated by the need for ATP

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