Ch. 19 Oxidative Phosphorylation

stage one of cellular respiration

oxidation of fuels to acetyl CoA

products of stage one of cellular respiration

ATP, NADH, FADH2

stage two of cellular respiration

oxidation of the acetyl groups to CO2 in the citric acid cycle

products of stage two of cellular respiration

NADH, FADH2, GTP

stage three of cellular respiration

electron transfer chain and oxidative phosphorylation

products of stage three of cellular respiration

ATP and H2O

what organelle is the central role in eukaryotic aerobic metabolism?

mitochondria

what is the final electron acceptor in the electron transport chain?

oxygen (O2)

what is the final product from inhaled O2 in the electron transport chain?

H2O

what is the final product from ingested fuel in the electron transport chain?

CO2

how is free energy made available in the context of the electron transport chain?

exergonic (downhill) electron flow is coupled to “uphill” transport of protons across a proton-impermeable membrane

how do proteins flow down the electrochemical gradient across the membrane?

specific protein channels

ATP synthase

couples proton flow to phosphorylation of ADP to ATP

what are the main reduced fuels for the cell?

carbohydrates, lipids and amino acids

where are electrons from reduced fuels transferred to?

reduced cofactors NADH and FADH2

oxidative phosphorylation in simple terms

energy from NADH and FADH2 are used to make ATP

where does the energy used to phosphorylate ADP come from

energy of oxidation

structure of mitochondrial outer membrane

relatively porous, allowing passage of metabolites

structure of mitochondrial inner membrane space (IMS)

• similar environment to cytosol

• higher proton concentration (lower pH) compared to the matrix

structure of mitochondrial inner membrane

• impermeable

• cristae increase surface area

• location of electron transport chain complexes

structure of mitochondrial matrix

lower proton concentration (higher pH) compared to IMS

what processes occur in the mitochondrial matrix?

citric acid cycle

parts of lipid and amino acid metabolism

the effect of stress on mitochondria

can trigger mitochondrial fission and mitophagy

mitophagy

the breakdown of mitochondria and recycling of the amino acids, nucleotides and lipids

chemiosmotic theory

proton concentration differences across the membrane drives ATP synthesis

if ADP + Pi → ATP is highly thermodynamically unfavorable, how is it possible?

the energy needed to phosphorylate ATP is given by protons flowing down the electrochemical gradient

how are protons transported against the electrochemical gradient?

the energy released by electron transport is used to transport protons against the electrochemical gradient

how is a proton gradient stabily established?

• the gradient occurs across a membrane that is impermeable to ions

• membrane must contain proteins that couples the “downhill” flow of electrons with the “uphill” flow of protons across the membrane

• membrane must contain a protein that couples “downhill” flow of protons to the phosphorylation of ADP

three steps of oxidative phosphorylation (in simple terms)

1. generation of high transfer potential electrons

2. flow of electrons through respiratory chain

3. synthesis of ATP

reduction potential

the affinity brethren an electron donor and its electrons

higher reduction potential (stronger oxidant)

greater tendency to gain electrons

lower reduction potential (weaker oxidant)

greater tendency to lose electrons

what is the reductant in biological electron transport?

NADH

how are electrons transferred?

the electron transport chain complexes that contain a series of electron carriers

does reduction potential increase or decrees across the electron transport chain?

increases

contents of the redox centers in the electron transport chain complexes

• flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD)

• cytochromes a, b or c

• iron-sulfur cluster

three ways electrons are transferred in oxidative phosphorylation

1. direct transfer (Fe3+ → Fe2+)

2. transfer of H atom (H+ + e-)

3. hydride ions (H-)

nicotinamide-containing carriers (NAD→NADH)

reduced to NADH

reduced with 2H atoms (2 electrons) at a time

flavin-containing characters (FAD→FADH/FADH2)

can reduce with a single electron (FADH) or two electrons (FADH2)

semiquinone

FAD after accepting only one electron (FADH)

cytochrome

• carries one electron

• iron coordinating porphoryin ring derivatives

three types of cytochromes

1. a-type

2. b-type

3. c-type

what cytochrome is in iron protoporphyrin IX?

b-type

what cytochrome is in heme c?

c-type

what cytochrome is in heme a?

a-type

structure of heme a

long isoprenoid tail attached to one of the five-membered rings

how is heme c bound to its protein?

thioester bonds to two cys residues

ubiquinone / coenzyme Q / Q properties

• lipid-soluble, can diffuse through mitochondrial inner membranes

• readily accepts electrons (1 or 2)

coenzyme Q function

transports electrons from complexes I and II to complex III

ubiquinol

• fully rescued coenzyme Q (accepted 2 electrons)

• an alcohol

ubisemiquinone

radical of coenzyme Q (only accepted 1 electron)

iron-sulfur clusters properties

• carries one electron

• coordinates by cysteines in the protein

• contains and equal number of iron and sulfur

how are iron-sulfur complexes named?

by the number of inorganic components (ie 2Fe-2S, 4Fe-4s)

what does the reduction potential of iron-sulfur clusters depend on?

• the type of the center

• the interaction with the associated protein

name of enzyme complex/protein I in the respiratory chain

NADH dehydrogenase

name of enzyme complex/protein II in the respiratory chain

succinate dehydrogenase

name of enzyme complex/protein III in the respiratory chain

ubiquinone cytochrome c oxioreductase

name of enzyme complex/protein IV in the respiratory chain

cytochrome oxidase

prothetic groups in enzyme complex/protein I in the respiratory chain

• FMN

• Fe-S

prothetic groups in enzyme complex/protein II in the respiratory chain

• FAD

• Fe-S

prothetic groups in enzyme complex/protein III in the respiratory chain

• hemes

• Fe-S

prothetic groups in enzyme complex/protein IV in the respiratory chain

• hemes

• Cu(a)

• Cu(b)

prothetic groups in enzyme complex/protein cytochrome c in the respiratory chain

heme

P side

positively charged, intermembrane space

N side

negatively charged matrix

which electron transport enzyme complex/protein is the largest?

complex I

what gives electrons to complex I?

NADH

how many electrons are accepted by complex I?

2 electrons

how do iron-sulfur center pass electrons?

one electron at a time toward ubiquinone binding site