Advanced Biochemistry

Advanced Biochemistry – Metabolism 45 questions assignment

Fundamentals of Biochemistry

Fourth Edition

Chapter 18 Electron Transport and Oxidative Phosphorylation

Donald Voet • Judith G. Voet • Charlotte W. Pratt

The Structure of the Mitochondrion A Few Aspects of Communication Between Cytosol and

Mitochondrion Overview of Electron Transport in Mito Membrane

Intro to Some New Players – Co-Enzyme Q, Fe-S proteins and Cytochromes

Organization of Electron Transport Generation of Proton Motive Force by Arrangement of e-

carriers ATP synthesis – ATPase is a machine

Overview: Oxidative Fuel Metabolism

Chapter 18 The Mitochondrion

Key Concepts 18.1 • A highly folded, protein-rich inner membrane separates the

mitochondrial matrix from the outer membrane.

• Transport proteins are required to import reducing

equivalents, ADP, and Pi into the mitochondria.

Animal Mitochondrion

Mitochondrion Cutaway Diagram

Mitochondrial Cristae

Inner Membrane Is Rich In Proteins

Glycerophosphate Shuttle

Bovine ATP-ADP Translocator: Ligand Induced Conformational Changes

Bovine heart ATP-ADP translocator PDBid 2C3E

Bovine ATP-ADP Translocator: Positively Charged Cavity Binds ATP

Bovine heart ATP-ADP translocator PDBid 2C3E

Chapter 18 The Mitochondrion

Checkpoint 18.1 • Draw a simple diagram of a mitochondrion and idenAfy its

structural features.

• Describe how shuBle systems transport reducing

equivalents into the mitochondria.

• Explain how the free energy of the proton gradient drives

the transport of ATP, ADP, and Pi.

Chapter 18 Electron Transport

Key Concepts 18.2 • The free energy of electron transport from NADH to O

2 can

drive the synthesis of approximately 2.5 ATP.

• Electron carriers are arranged in the mitochondrial

membrane so that electrons travel from Complexes I and II

via coenzyme Q to Complex III, and from there via

cytochrome c to Complex IV. • The L-shaped Complex I transfers electrons from NADH to

CoQ via a series of iron–sulfur clusters and translocates four

protons to the intermembrane space.

Chapter 18 Electron Transport

Key Concepts 18.2 • Complex II transfers electrons from succinate to the CoQ

pool but does not contribute to the transmembrane proton

gradient.

• Electrons from Complex III are transferred to cytochrome c and two protons are translocated during the operaAon of the Q cycle in Complex III.

• Complex IV accepts electrons from cytochrome c to reduce O

2 to H

2 O and translocates four protons for every two

electrons transferred.

Overview of Electron Transport

air

vectory arrangement of alternating carries the electron and proton or the electron only

air

damp on the other side

Inhibitors Reveal Electron-Transport Chain Sequence of Events

Reduction Potentials of ETC Components

Mitochondrial Electron-Transport Chain

Iron-Sulfur Clusters

Complex I

Complex I from Thermus thermophilus PDBid 3M9S

Oxidation States of FMN & CoQ

Peripheral Arm of Complex I

Thermus thermophilus PDBid 2FUG

Redox Active Prosthetic Groups Peripheral Arm of Complex I

Thermus thermophilus PDBid 2FUG

Complex II

Chicken Complex II PDBid 1YQ3

Box 18-1: Cytochromes are Electron -Transport Heme Proteins

Complex III

Yeast Complex III PDBid 1KYO

The Q Cycle

Stigmatellin Blocks Qo Site

Cytochrome c

Complex IV

Bovine heart cytochrome c oxidase homodimer PDBid 1V54

Redox Centers of Complex IV

Proposed Reaction Sequence for Complex IV

Chapter 18 Electron Transport

Checkpoint 18.2 • Describe the route followed by electrons from glucose to O

2 .

• Write the net equaAon for electron transfer from NADH to

O 2 .

• Assuming 100% efficiency, calculate the maximum amount of

ATP that could be synthesized as a result.

• For each of the electron-transport complexes, write the

relevant redox half-reacAons.

• PosiAon the four electron-transport complexes on a graph

showing their relaAve reducAon potenAals, and indicate the

path of electron flow.

• How did inhibitors reveal the order of electron transport?

Chapter 18 Oxidative Phosphorylation

Key Concepts 18.3 • The chemiosmoAc theory explains how a proton gradient

links electron transport to ATP synthesis.

• ATP synthase consists of an F1 component that catalyzes

ATP synthesis by a binding change mechanism.

• The F0 component of ATP synthase includes a c-ring whose rotaAon is driven by the dissipaAon of the proton gradient

and drives conformaAonal changes in the F1 component.

• For every two electrons that enter the electron-transport

chain as NADH and reduce one oxygen atom, approximately

2.5 ATP molecules are produced, giving a P/O raAo of 2.5.

• Agents that dissipate the proton gradient can uncouple

electron transport and ATP synthesis.

Coupling of Electron Transport and ATP Synthesis

Box 18-3: Bacterial Electron Transport & Oxidative Phosphorylation

F1 Components of ATP Synthase Protrude From Mitochondrial Cristae

F1 Component of ATP Synthase

Bovine F1-ATP synthase PDBid 1E79

Model of F1F0-ATPase

F1F0-ATPase PDBids 1JNV, 2A7U, and 1B9U

Binding Change Mechanism for ATP Synthase

Inner Sleeve of F1 α3β3 Assembly Interacts with γ-Subunit

F1 α3β3 PDBid 1BMF

Model of F1F0-ATPase

pH-Dependent Conformational Change of c Subunit of F1F0-ATPase

C subunit of E. coli F1F0-ATPase PDBid 1COV

ATP-Dependent Rotation of c-Ring From F1F0-ATPase

Nonphysiological Electron Donor Yields ATP

Oxidative Phosphorylation Can Be Uncoupled From Electron Transport

Chapter 18 Oxidative Phosphorylation

Checkpoint 18.3 • Summarize the chemiosmoAc theory.

• Explain why an intact, impermeable mitochondrial membrane

is essenAal for ATP synthesis.

• Describe the overall structure of the F1 and F0 components of

ATP synthase. Which parts move? Which are staAonary? Which

are mostly staAonary but undergo conformaAonal changes?

• Summarize the steps of the binding change mechanism.

• Describe how protons move from the intermembrane space

into the matrix. How is proton translocaAon linked to ATP

synthesis?

• Explain why the P/O raAo for a given substrate is not

necessarily an integer.

• Explain how oxidaAve phosphorylaAon is linked to electron

transport and how the two processes can be uncoupled.

Chapter 18 Control of Oxidative Metabolism

Key Concepts 18.4 • The rate of oxidaAve phosphorylaAon is coordinated with

the cell s other oxidaAve pathways.

• Although aerobic metabolism is efficient, it leads to the

producAon of reacAve oxygen species.

Box 18-4: Uncoupling in Brown Adipose Tissue Generates Heat

Coordinated Control of Glycolysis and the Citric Acid Cycle

Box 18-5: Oxygen Deprivation in Heart Attack & Stroke

Electrostatic Effects in SOD

Proc Natl Acad Sci U S A. 1991 Jun 1; 88(11): 4870–4873. Mitochondrial respiration in hummingbird flight muscles. R K Suarez, J R Lighton, G S Brown, and O Mathieu-Costello Abstract Respiration rates of muscle mitochondria in flying hummingbirds range from 7 to 10 ml of O2 per cm3 of mitochondria per min, which is about 2 times higher than the range obtained in the locomotory muscles of mammals running at their maximum aerobic capacities (VO2max). Capillary volume density is higher in hummingbird flight muscles than in mammalian skeletal muscles. Mitochondria occupy approximately 35% of fiber volume in hummingbird flight muscles and cluster beneath the sarcolemmal membrane adjacent to capillaries to a greater extent than in mammalian muscles. Measurements of protein content, citrate synthase activity, and respiratory rates in vitro per unit mitochondrial volume reveal no significant differences between hummingbird and mammalian skeletal muscle mitochondria. However, inner membrane surface areas per unit mitochondrial volume [Sv(im,m)] are higher than those in mammalian muscle. We propose that both mitochondrial volume densities and Sv(im,m) are near their maximum theoretical limits in hummingbirds and that higher rates of mitochondrial respiration than those observed in mammals are achieved in vivo as a result of higher capacities for O2 delivery and substrate catabolism.

Mitochondrial responses to prolonged anoxia in brain of red-eared slider turtles Matthew E. Pamenter, Crisostomo R. Gomez, Jeffrey G. Richards, William K. Milsom Published 13 January 2016.DOI: 10.1098/rsbl.2015.0797 /.panel-row-wrapper. “Biology Letters” Mitochondria are central to aerobic energy production and play a key role in neuronal signalling. During anoxia, however, the mitochondria of most vertebrates initiate deleterious cell death cascades. Nonetheless, a handful of vertebrate species, including some freshwater turtles, are remarkably tolerant of low oxygen environments and survive months of anoxia without apparent damage to brain tissue. This tolerance suggests that mitochondria in the brains of such species are adapted to withstand prolonged anoxia, but little is known about potential neuroprotective responses. In this study, we address such mechanisms by comparing mitochondrial function between brain tissues isolated from cold-acclimated red-eared slider turtles (Trachemys scripta elegans) exposed to two weeks of either normoxia or anoxia. We found that brain mitochondria from anoxia -acclimated turtles exhibited a unique phenotype of remodelling relative to normoxic controls, including: (i) decreased citrate synthase and F1FO-ATPase activity but maintained protein content, (ii) markedly reduced aerobic capacity, and (iii) mild uncoupling of the mitochondrial proton gradient. These data suggest that turtle brain mitochondria respond to low oxygen stress with a unique suite of changes tailored towards neuroprotection.

Chapter 18 Control of Oxidative Metabolism

Checkpoint 18.4 • How do the ATP mass acAon raAo and the IF1 protein

regulate ATP synthesis?

• What control mechanisms link glycolysis, the citric acid

cycle, and oxidaAve phosphorylaAon?

• Describe the advantages and disadvantages of oxygen

-based metabolism.

• How do cells minimize oxidaAve damage?

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