2.5 [BIOCHEMISTRY] Electron Transport Chain and Oxidative Phosphorylation

[BIOCHEMISTRY] 2.5 [BIOCHEMISTRY] 2.5 Electron Transport Chain and Oxidative Phosphorylation [BIOCHEMISTRY] 2.5 [BIOCHEMISTRY] 2.5 Electron Transport Chain and Oxidative Phosphorylation – Phosphorylation – Balcueva, Balcueva, MD Dr. Balcueva 7 August 2013 14 – 14 – Estacion, Estacion, Estillore, Estrada, Eugenio, Fabiania, Fandiño, Favila, Fegarido, Feliciano

OUTLINE

Enzymes in the Outer Membrane 1. Acyl Coenzyme A synthetase 2. Glycerolphosphate acyl transferase

I. Mitochondria II. Respiratory Chain and Oxidative Phosphorylation A. Respiratory Chain B. Oxidative Phosphorylation at the Respiratory Chain III. Oxidative Phosphorylation IV. ATP Synthesis A. Proton Translocation and ATP Synthesis B. ATP Synthase and Couplers V. Respiratory Control VI. Substrate Shuttles VII. Clinical Correlations VIII. Summary IX. Competencies X. Sample problems

*Same enzyme located in the cytosol

Enzymes in the Inner Membrane 1. Electron carriers – – 4 complexes responsible for oxidizing the different reducing coenzymes 2. ATP synthase 3. Membrane transporters 4. Cardiolipin – – a phospholipid that is concentrated in the inner membrane together with the enzymes of the respiratory chain, ATP synthase, and various membrane transporters (Harper ’s ’s Chapter 13, p. 122 122). ). Enzymes in the Mitochondrial Matrix 1. Citric Acid Cycle 2. Pyruvate dehydrogenase – dehydrogenase – produces produces NADH 3. ß-oxidation enzymes

OBJECTIVES At the end of the lecture, the student should be able to: 1. To develop understanding of the st ructural organization of the mitochondria; 2. To develop an underst anding of the c oupling mechanism between oxidation of reducing equivalents and ATP synthesis; and 3. To identify poisons/toxins that block the Electron Transport Chain (ETC) and ATP synthesis References: References: Harper’s Illustrated Biochemistry Transes from previous batches Legend: Italicized – – quoted from the lecturer; bold – – emphasis, or from references

I. MITOCHONDRIA - Mitochondria have an outer membrane membrane which is permeable to most molecules and inner membrane which is selectively permeable, enclosing a matrix within. Inner membrane is not permeable to ionized molecules. Review: Enzymes in the Citric Acid Cycle that will form NADH include Pyruvate dehydrogenase, dehydrogenase, Isocitrate dehydrogenase, dehydrogenase, α-ketoglutarate dehydrogenase, dehydrogenase, and malate dehydrogenase. dehydrogenase. While for FADH, the enzyme is Succinate dehydrogenase. dehydrogenase. NADH and FADH store the energy that is released so that the energy is not wasted; rather they are transported to electron chain and converted to ATP. NADH and FADH represent the reducing equivalents, brought to ETC to oxidize bringing in the oxygen, which will be reduced to water.

Figure 2. Structure of the mitochondrial mitochondrial membranes. (Harper’s (Harper’s p. 122)

II. RESPIRATORY CHAIN AND OXIDATIVE PHOSPHORYLATION - Mitochondria contains the respiratory chain that that collects and and transports reducing equivalents such as NADH and FADH (H or electrons) to oxygen - Oxygen oxidizes reducing equivalents equivalents to form water at the end of the chain - Oxidation is coupled to ATP formation from ADP and inorganic phosphate (Pi) A. Respiratory Chain - H+ and electrons flow through through the respiratory chain in in order of decreasing redox potential (NADH = -0.32 volts (highest redox potential); fumarate/succinate = +0.8 volts) - In reactions involving oxidation-reduction, oxidation-reduction, the ability of the reactants to donate or accept electrons is proportionate to free energy (redox potential) - Redox potential of a system system is compared to redox potential of a hydrogen electrode at -0.42 volts

Figure 1. Role of the respiratory chain of mitochondria in the conversion of food energy energy to ATP. (Harper’s p. 123)

- [1] 14 - Estacion, Estillore, Estillore, Estrada, Eugenio, Fabiania, Fandiño, Favila, Fegarido, Feliciano

[BIOCHEMISTRY] 2.5 [BIOCHEMISTRY] 2.5 Electron Transport Chain and Oxidative Phosphorylation – Phosphorylation – Balcueva, Balcueva, MD - Consists of redox carriers that start with NAD/NADH to O2/2H2O - Fumarate/succinate Fumarate/succinate bypass NAD/NADH and are linked to flavoprotein dehydrogenases - Ubiquinone (Q): • Structure similar similar to vitamin vitamin K and E; • Mobile component component of the respiratory respiratory chain • Collects reducing reducing equivalents equivalents from flavoprotein

Complex I (NADH-Q I (NADH-Q oxidoreductase)

Table 1. Standard Reduction Potentials of Respiratory Chain and Related Electron Carriers.

Figure 4. Complex I of Respiratory Chain.

NADH + Q + 5H+ → NAD + QH2 + 4H+

- Catalyzes electron transfer from NADH to Q, coupled with + the transfer of 4 H across the membrane - Electrons are transferred from NADH to FMN initially, then to a series of Fe-S centers and finally to Q. (Harper) - 4 protons produced - Flow of e : NADH → FMN → Fe Fe--S centers → Q

Overview of the Process of electron flow via Respiratory Chain - Electrons flow through the Respiratory Chain via redox carriers that start from NAD/NADH to O 2 /2H 2 2O through a redox span of 1.1 V (Harper ’ ’s) s ) - Electrons Passes through three Large Protein Complexes: 1. Com plex I (NADH-Q oxido reduc tase)

Electrons transferred from NADH → Q 2 . C o m p l e x I II II ( Q -c -c y t o c h r o m e c o x i d o r e d u c t a s e )

passes the electrons electrons from Q → cyt c 3 . C o m p l e x I V (c (c y t o c h r o m e c o x i d a s e )

Figure 5. Coenzyme Q.

Completes the chain Passing the electrons to O2, reducing it to water - Fumarate/succinate Fumarate/succinate has a more positive positive redox potential potential than NAD/NADH. Gives electrons ability to bypass bypass the utilization of NAD/NADH and Complex I Thus, Electrons pass directly directly to Q via Complex II (Succinate-Q reductase ) reductase )

Complex II (Succinate-Q II (Succinate-Q reductase) - FADH2 is formed during the conversion of succinate to fumarate in the citric acid cycle and electrons are passed via several Fe-S centers to Q. - Flow of e : FAD (from (from succinate) → FeFe -S centers → Q

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B. Oxidative Phosphorylation at the Respiratory Chain - NADH – NADH – 3 3 moles of Pi are incorporated to 3 ADPs - FADH – FADH – 2 2 moles of Pi are incorporated to 2 ADPs - P:O = 3 - Free energy from glucose through substrate phosphorylation phosphorylation (103kJ/mol glucose) - Free energy through respiratory respiratory chain (68%)

Figure 6. Coenzyme Q and Complex III.

Figure 7. Succinate/Fumarate, CoQ, and Complexes II and III.

Figure 3. Oxidative Phosphorylation at the Respiratory Chain. Chain . (Harper’s p. 124)


[BIOCHEMISTRY] 2.5 [BIOCHEMISTRY] 2.5 Electron Transport Chain and Oxidative Phosphorylation – Phosphorylation – Balcueva, Balcueva, MD Complex III (Q-cytochrome III (Q-cytochrome c oxidoreductase)

• May contain one, two, or four Fe atoms atoms via cysteinecysteinethiol (SH) groups except in complex III, where Fe is linked to a histidine-SH group (Rieske Fe-S)

QH2 + 2 Cytc(o) + 2H (matrix) → Q + 2 Cytc(r) + 4H

- This process is believed to involve involve cytochromes cytochromes c 1, bL and bh, and a Rieske Fe-S (an unusual Fe-S in which one of the Fe atoms is linked to two histidine residues rather than two cysteine residues) (Harper). - aka the Q cycle Q exists in 3 forms: Oxidized quinone (Q), Reduced quinol (QH2), and Semiquinone (Harper) - Oxidation of QH2 to Q 1st e is donated to cyt c via a Rieske Fe-S and cyt c 1 2nd e is donated to a Q to form the semiquinone via cyt bL and cyt bH + 2 H are released into the intermembrane space - Oxidation of a second QH2 to Q 1st e is donated to cyt c via a Rieske Fe-S and cyt c 1 2nd e is donated to the semiquinone, reducing it to QH 2 + Another 2 H are released into the intermembrane space + 2 H are taken up into the inner mitochondrial membrane from the matrix - 4 protons produced - Flow of e : QH2 → Rieske FeFe-S → cytochrome c •

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Figure 9. Fe-S proteins. proteins. (Harper’s p. 124)

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III. OXIDATIVE PHOSPHORYLAT PHOSPHORYLATION ION Chemiosmotic Theory - Peter Mitchell (1961) proposed mechanism for oxidative phosphorylation - The H+ ion transfer results in an increase in the H+ ion concentration in the space between the inner and outer mitochondrial membranes. It is necessary to move H+ ions back across the membrane. This transfer of H+ ions is necessary in the synthesis of ATP. - It assumes that the H+ ion gradient is a significant factor factor promoting the conversion of ADP to ATP, occurring in the four complexes present in the inter mitochondrial membrane result in a net transfer of H+ ions across the membrane. - Energy from oxidation of components in the respiratory chain is coupled to the translocation of hydrogen ions from the inside to the outside of the inter mitochondrial membrane space.

Figure 8. Complex IV

Complex IV (Cytochrome IV (Cytochrome c oxidase) 4 Cytc(r) + O2 + 8H → 4 Cytc(o) + 2 H2O + 4H -

- Transfer of 4 e from Cyt c to O 2 involves two heme groups, a and a3, and Cu - Electrons are passed initially to a Cu center (Cu A). - Cu A contains 2 Cu atoms linked to 2 protein Cysteine-SH groups - A second second Cu center, CuB, is linked to heme a3 + - Of the 8 H removed from the matrix, o 4 are used to form 2 H2O space o 4 are pumped into the intermembrane space - Thus, for every pair of e- passing down the chain from + NADH or FADH2, 2 H are pumped across the membrane by Complex IV - O2 remains tightly bound to Complex IV until it is fully reduced - This minimizes the release of potentially damaging intermediates, such as superoxide anions or peroxide, whic h are formed when O2 accepts 1 or 2 e , respectively + - 2 protons produced . Based on the reaction given above, 4H were released in the intermembrane space. This is because + the 4H released reacted with O2 forming water. Flow of e : Cyt c → Cu A → heme a → heme a3 and CuB → O2

Figure 10. Electrochemical Electrochemical gradient.

Enzymes Involved in Oxidation-Reduction Reaction (Oxidoreductases) 1. Oxidases • Remove hydrogen from a substrate using using oxygen as an acceptor • Forms water water or hydrogen peroxide a. Cytochrome oxidase o Located in Complex IV o Has a heme prosthetic group chain o Terminal component of the chain oxygen (tightly bound to o Carries electron to oxygen Complex IV) a. Flavoproteins contain flavin adenine dinucleotide (FAD)

Components of the Respiratory Chain Complexes 1. Flavoproteins: Flavoproteins: Complexes I and II a. FMN → FMNH2 b. FAD → FADH2 2. Fe-S: Fe-S: Complexes I, II, and III


[BIOCHEMISTRY] 2.5 [BIOCHEMISTRY] 2.5 Electron Transport Chain and Oxidative Phosphorylation – Phosphorylation – Balcueva, Balcueva, MD 2. Dehydrogenases • Transfer hydrogen from one substrate to to another • Cannot use O2 as a hydrogen acceptor specific for the substrate; uses coenzymes or hydrogen acceptors • Example: NAD and FAD dehydrogenase dehydrogenase

B. ATP Synthase and Couplers

3. Hydroxyperoxidases • Use oxygen as hydrogen peroxide or organic peroxide as substrate • Protects the the body against against harmful peroxides 4. Oxygenases • Catalyze direct transfer • Incorporation of oxygen oxygen into a substrate

Figure 12. Complexes I, II, III, and IV acts as proton pumps . (Harper’s, p. 126)

ATP Synthase Complex - also called Complex V - Driven by the proton motive force force - Functions as a rotary motor to form ATP ATP in the presence of Pi + ADP - It is composed of two parts: F 0 and F 1 0 and - F1 – for – for binding of ATP & ADP - F0 – for – for translocation of protons F1 subcomplex - Projects into the matrix - Contains the the phosphorylation phosphorylation mechanism - Attached to F0 through the γ subunit, which is in the form of a “bent axle” - Consists of 3 α and 3 β subunits attached around the γ subunit. The α and β subunits are fixed into the membrane and do not rotate with the γ subunit

Figure 11. Overview of the electron flow through the respiratory chain. (Harper’s (Harper’s p. 123)

IV. ATP SYNTHESIS A. Proton Translocation and ATP Synthesis - Complex I, III and IV acts as proton pumps, creating a proton gradient across the membrane negative on the matrix side - Complex I and III – III – translocate translocate 4 protons each - Complex IV – IV – translocate translocate 2 protons - H ions enter or pass across the inner mitochondrial membrane thru the ATP synthase w/ ATP synthesis - ATP cannot be generated without the protons which are transferred into the inter membrane space - ATP goes out in exchange of ADP: anti-port - Electron chemical chemical gradient gives rise to Proton Motive Motive Force

F0 subcomplex - Spans the membrane - Consists of several “C” protein subunits which form a disk - Forms a proton channel - Protons re-enter the membrane membrane via F0, causing it (and the attached γ subunit) to rotate to the right, driving the production of ATP in the F 1 complex Binding Change Mechanism - The conformation of the β-subunits β-subunits in F1 is changed as the axis rotates from one that binds ATP tightly to one that releases ATP and binds ADP and Pi so that the next ATP can be formed - F 1 is squeezed causing the release of ATP; β portion of the membrane contains ADP and Pi, with the action of ATP synthase ATP is produced

Proton Motive Force - Drives ATP synthesis as proton proton flow back into the matrix with the help o f ATP synthase enzyme - Caused by the the electrochemical electrochemical potential difference - Protons accumulate in the intermembrane space because because the inner mitochondrial membrane is impermeable to ions - Thus, negative ( –) –) on the matrix side - Recall: Complexes Complexes I, III, III, and IV act as proton pumps - Protons from the matrix → across inner mitochondrial membrane → into the intermembrane space

Mechanism of ATP Production by ATP Synthase

Uncouplers - Increases membrane membrane permeability permeability to ions - Collapses proton gradient - Allows H+ to pass pass without going going through the ATP synthase - Results in the flow flow of uncouple electron through respiratory complexes from ATP synthesis


[BIOCHEMISTRY] 2.5 [BIOCHEMISTRY] 2.5 Electron Transport Chain and Oxidative Phosphorylation – Phosphorylation – Balcueva, Balcueva, MD - Malonate is a competitive inhibitor of succinate dehydrogenase in Complex II. (Also carboxin and thenoyltrifluoroacetone.. All with succinate as substrate. thenoyltrifluoroacetone - Antimycin A, BAL and dimercaprol inhibits between Cytochrome b and c in Complex III by blocking electron transfer from cytochrome heme bH to ubiquinone. - Others such as myxothiazol and stigmatellin inhibit transfer through complex III by binding to the Q0 site and blocking transfer of electrons from ubiquinol. - H2S, carbon monoxide and cyanide inhibits cytochrome oxidase in Complex IV and can therefore totally arrest respiratory chain. - The antibiotic oligomycin completely blocks oxidation and phosphorylation. - Uncouplers (e.g. 2,4- dinitrophenol dinitrophenol) dissociate oxidation in the respiratory chain from phosphorylation. It causes respiration to be uncontrolled, in vivo, since the rate is no longer limited by the concentration of ADP and Pi. Thermogenin Thermogenin (the uncoupling protein) is a physiologic uncoupler found in brown tissue that functions to generate body heat, particularly for the newborn and during hibernation. - Atractyloside inhibits Atractyloside inhibits oxidative phosphorylation by inhibiting the transporter of ADP into and ATP out of the mitochondrion.

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Alternating alpha and beta subunits subunits form knob of F1 Protons flow through membrane First bind to amino acid in F o Protons then bind to to amino acid residue residue on C subunit Gamma and epsilon units rotate Gamma subunit movement movement cause cause change in beta subunit A and B units of Fo + delta subunit of F 1 = stator to hold alpha and beta subunits in place - Gamma and c subunits form the rotor rotor

Table 2. Summary of Inhibitors of the Respiratory Chain and Oxidative Phosphorylation

Figure 14. Exchange diffusion systems. (Harper’s, p. 129)

POISON SITE OF ACTION Inhibitors of the Respiratory Chain Barbiturates Complex I Antimycin A Complex III Dimercaprol H2S Complex IV Carbon Monoxide Cyanide Malonate Complex 2 Inhibitors of Oxidative Phosphorylation Phosphorylation Atractyloside Oxidative Phosphorylation Phosphorylation Oligomycin Halts both Oxidation and Phosphorylation Uncouplers: Halts coupling of oxidation and 2, 4-dinitrophenol phosphorylation Thermogensin (protein in brown adipose tissue)

V. RESPIRATORY CONTROL - Because oxidation and phosphorylation phosphorylation are tightly coupled, coupled, the rate of respiration of mitochondria can be controlled by the availability of ADP. - Most cells in the resting state state are in State 4. STATE State 1 State 2 State 3 State 4 State 5

CONDITIONS LIMITING RATE OF RESPIRATION Availability of ADP and substrate Availability of substrate only Availability of ADP only Capacity of the respiratory chain Availability of oxygen only

Inhibitors of Oxidation-Phosphorylation Oxidation-Phosphorylation

VI. SUBSTRATE SHUTTLES - NADH cannot penetrate the mitochondrial membrane, but it is produced continuously in the cytosol by 3phosphoglyceraldehyde dehydrogensase (enzyme in glycolysis). - However, under aerobic conditions, extramitochondrial extramitochondrial NADH does not accumulate and is presumed to be oxidized by the respiratory chain in mitochondria. - The transfer of reducing equivalents through the mitochondrial membrane requires substrate pairs (SHUTTLES), linked by suitable dehydrogensases on each side of the mitochondrial membrane. A. Malate-Aspartate Shuttle - NADH binds with Complex Complex I - Found in liver, liver, kidney and heart mitochondria mitochondria - ATP produced: 3 (but in actuality 2.5) - Occurs in HKL – HKL – heart, heart, kidney, liver - Universally used shuttle

Figure 15. Sites of inhibition of the respiratory chain by specific drugs, chemicals, and antibiotics. (Harper’s, p. 128)

- Barbiturates like amobarbital ,piercidin & amytal inhibit NAD-linked Dehydrogenase by blocking the transfer from FeS to Q in Complex I by preventing transfer of electrons from iron sulphur centers to ubiquinone.


[BIOCHEMISTRY] 2.5 [BIOCHEMISTRY] 2.5 Electron Transport Chain and Oxidative Phosphorylation – Phosphorylation – Balcueva, Balcueva, MD

Figure 16. Malate- Aspartate Aspartate shuttle. (Harper’s, (Harper’s, p. 130)

How It Works: i. NADH reduces oxaloacetate to form malate in the intermembrane space by malate dehydrogenase ii. Malate enters the matrix via the Malate- α-ketoglutarate transporter iii. Malate reduces NAD+ to form NAD + H+ and oxaloacetate oxaloacetate in the matrix by malate dehydrogenase iv. Oxaloacetate is transaminated by glutamate to form Aspartate and α-ketoglutarate by aspartate aminotransferase v. Aspartate leaves the matrix via Glutamate-aspartate transporter vi. Aspartate is deaminated by α -ketoglutarate forming oxaloacetate and glutamine

Figure 18. Transporter systems in the inner mitochondrial membrane. (Harper’s, p. 128)

B. Glycerol-3-Phosphate Shuttle - NADH binds with Complex Complex II - ATP produced: 2 (but in actuality, 1.5) - Occurs in brain and white muscle muscle - Deficient in heart

Figure 17. Glycerophosphate shuttle. (Harper’s, (Harper’s, p. 130)

How it works: i. Dihydroxyacetone phosphate is reduced by NADH + H+ in the cytosol to form glycerol 3-phosphate. The reaction is catalyzed by cytosolic glycerol 3-phosphate dehydrogenase ii. Mitochondrial glycerol 3-phosphate dehydrogenase (reduction) transfers the electrons from glycerol 3 -phosphate to FAD to form FADH2 and dihydroxyacetone phosphate iii. The electrons are then then transferred transferred to ubiquinone

Figure 19. The Creatinine Phosphate Phosphate shuttle. (Harper’s, p. 131)


[BIOCHEMISTRY] 2.5 [BIOCHEMISTRY] 2.5 Electron Transport Chain and Oxidative Phosphorylation – Phosphorylation – Balcueva, Balcueva, MD VII. CLINICAL CORRELATIONS 1. Fatal infantile mitochondrial myopathy myopathy and renal dysfunction is dysfunction is the severe deficiency of the oxidoreductase enzymes in the ETC. 2. MELAS is MELAS is the deficiency of NADH-Q or cytochrome oxidase. An inherited condition due to NADH-Q oxidoreductase (Complex I) or cytochrome oxidase (Complex IV) deficiency. It is caused by a mutation in mitochondrial DNA and may be involved in Alzheimer's disease and diabetes mellitus. mellitus. 3. Brown adipose tissue is tissue is a cold-induced thermogenesis due to production of uncoupling protein (UCP-1) that carries protons from the mitochondrial matrix and uncouples ATP synthesis from respiration. 4. Leber is is a hereditary optic neuropathy with sudden onset blindness from optic nerve death and results from single base mutation in genes encoding complex I. • •

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VIII. SUMMARY Most of the energy released during the oxidation of different food trapped as reducing equivalents that are oxidized in the respiratory chain. Oxidation of reducing equivalents is tightly coupled coupled to ATP production through ATP synthase. Protons or electrons are passed on through a series of reductants and oxidants in the ETC to oxygen in complex IV to form water. Oxidation through the different complexes also servs as a proton pump that translocates protons into the inter membrane space producing a Chemiosmotic gradient for ATP synthesis.

IX. COMPETENCIES 1. Given a normal person, identify biochemical pathways or processes involved in ATP production in the mitochondria. 2. Apply the biochemical concepts and principles that will help explain the development of diseases associated with defects in t he electron transport system and oxidative phosphorylation. 3. Correlate the biochemical or molecular basis with the clinical manifestation of the disease, the findings on physical examination o f the patient and laboratory results. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

11. 12. 13. 14. 15. 16.

X. SAMPLE QUESTIONS Identify the different layers of the mitochondrial mitochondrial membrane membrane and the enzymes enzymes that they contain. In applying your knowledge knowledge of the process process of Respiratory Chain, arrange its components components with regards to the electron electron flow. Complex I, Complex II, Complex III, Complex IV, Q, cyt c : ___/___>___>___>___>___ Match Flavoprotein and Fe-S Fe-S to their respective respective complexes. It states that that the electrochemical electrochemical potential difference from the the asymmetric distribution of the H+ drives the mechanism for ATP formation. Where is respiratory chain embedded? In what complex in ETC catalyzes electron electron transfer transfer from FADH2 to Q. What mechanism mechanism does the ATP synthase utilize to produce produce ATP? ATP? How does barbituates affect inhibit NAD-linked dehydrogenases? How does malonate affect the function of succinate succinate dehydrogenase? Arrange the following to the right sequence of ATP ATP production by ATP ATP synthase. a. F0 and the bent axle rotate counter-clockwise b. H+ crosses the membrane into the matrix via F0 c. B subunits bind ADP+Pi forming the next ATP d. F1 squeezed, causing change in conformation of B subunits e. ATP released What are the end products products of respiratory chain? T/F. Aerobic organisms are able to capture far greater proportion of available free energy of respiratory substrates than anaerobic organisms. How many ATPs ATPs are produced per revolution revolution of ATP synthase? synthase? T/F. Ubiquinone and cytochrome cytochrome are embedded in the inner membrane of the Mitochondria Mitochondria Sites electrons pass before going to to Q from complex 1. Which Fe-S is involved in the transport transport of electrons from Qh2 Qh2 to cytochrome c?

Answers: 1. See Page 1 of trans 2. I/II>Q>III>cyt c>IV 3. I,II/I,II,III 4. Chemiosmotic Theory 5. Inner Mitochondrial Membrane 6. Complex II 7. Binding Change mechanism 8. Blocking transfer from FEs to Q in complex I & preventing transfer of electrons 9. Through competetive inhibition 10. b>a>d>e>c 11. Water and ATP 12. T 13. 3 14. F, they are free flowing 15. FMN, Fe-S 16. Rieske FE-s


2.5 [BIOCHEMISTRY] Electron Transport Chain and Oxidative Phosphorylation

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