Biological oxidation
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Biological oxidation



Biological oxidation

Biological oxidation



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    Biological oxidation Biological oxidation Presentation Transcript

      • Oxidation is a reaction with oxygen directly or indirectly OR to lose hydrogen and / or electrons. This process is carried out by enzymes.
      • There can be the following three classes of biological oxidation :-
      • - loss of one or more electrons
      • - loss of one or more hydrogen atoms
      • - addition of one or more oxygen atoms
      • In exergonic reactions, free energy is released while in endergonic reactions, free energy is absorbed.
      • This free energy moves between the two reactions through the common intermediate . This common intermediate is thus a carrier of chemical energy between the two reactions.
      • Two chemical reactions have a common intermediate when they occur in a sequence. For example
      • A + B -> C + D
      • D + X -> Y + Z
      • D is the common intermediate and can act as carrier of chemical energy.
      • Many coupled reactions use ATP to generate common intermediate. These reactions may involve
      • ATP cleavage --- the transfer of a phosphate group from ATP to another molecule
      • ATP synthesis ---- the transfer of phosphate group from an energy rich intermediate to ADP, forming ATP.
    • Energy carried by ATP
      • ATP ---- one molecule of adenosine ( adenine + ribose ) , and three phosphate groups.
      • The phosphate groups are attached to each other by high-energy phosphate bonds.
      • -Removal of one phosphate ->-> ADP
      • -Removal of two phosphates ->-> AMP
      • The standard free energy of hydrolysis of ATP , is approx. – 7.3 kcal/mol for each of the two terminal phosphate groups.
      • During the metabolism of energy rich molecules, the metabolic intermediates of these reactions donate electrons to specific co-enzymes– NAD and FAD to form energy rich reduced coenzymes, NADH and FADH 2 . These reduced coenzymes, in turn each donate a pair of electrons to special electron carriers, collectively called Electron Transport Chain.
      • Free energy is lost by these electrons as they pass down this chain.
      • Part of this energy is used to form ATP from ADP – OXIDATIVE PHOSPHORYLATION.
      • The remainder of this energy is used in processes like Ca transport and to form heat.
    • Site of ETC
      • MITOCHONDRIA ---- inner mitochondrial membrane. It is impermeable to most small ions, small and large molecules --- requirement of specialized carriers.
      • The matrix of mitochondria contains
      • - TCA cycle enzymes
      • - fatty acid oxidation enzymes
      • - Mitochondrial DNA and RNA
      • NAD and FAD
      • ADP and Pi
    • Organization of the chain
      • The inner mitochondrial membrane can be divided into five protein complexes :-
      • - complexes I, II, III, IV, and V
      • Complex I to IV, each contains a part of the ETC. Complex V is used for ATP synthesis.
      • Each complex accepts or donates electrons to electron carriers --- coenzyme Q and Cytochrome c.
      • Each carrier donates electrons to the next carrier in the chain.
      • The electrons ultimately combine with oxygen and protons to form water.
    • Reactions of the electron transport chain
      • 1- Formation of NADH:-
      • NAD is reduced to NADH
      • Enzyme --- dehydrogenase --- removal of two hydrogen atoms from the substrate ---- both electrons and a hydride ion are transferred to NAD , forming NADH and a hydrogen ion.
      • 2 – NADH Dehydrogenase :-
      • NADH transfers the free proton and the hydride ion to NADH dehydrogenase --- complex I.
      • FMN is already present in this complex. It receives two hydrogen atoms and becomes FMNH 2.
      • 3- Coenzyme Q :-
      • It is a quinone derivative. Also called ubiquinone.
      • It can accept hydrogen atoms from two sources --- FMNH 2 ( complex I ) and from FADH 2 , produced on succinate dehydrogenase ( complex II ).
      • CoQ links flavoporoteins to cytochromes.
      • 4- Cytochromes :-
      • Each cytochrome contains a heme group made of a porphyrin ring with an iron atom.
      • The iron in cytochromes is converted from its ferric- Fe 3 to ferrous-Fe 2 form and functions as a reversible carrier of electrons.
      • The electrons are passed along the chain from coQ to cytochromes b and c1 ( complex III ), c and a + a 3 ( complex IV ).
      • 5- Cytochrome a + a 3 :-
      • Also called cytochrome oxidase.
      • At this site, transported electrons, molecular oxygen and free protons come together to produce water.
    • Release of free energy during ETC:-
      • Free energy is released during the transfer of electrons along the electron transport chain.
      • Coupled oxidation – reduction reactions --- Redox pairs e.g NADH -> NAD and FMN-> FMNH 2 .
      • Redox pairs differ in their tendency to lose electrons.
      • The transport of a pair of electrons from NADH to oxygen releases 52.58 calories--- used mainly for ATP formation.
      • Coenzyme Q (CoQ, Q or ubiquinone) is lipid-soluble. It dissolves in the hydrocarbon core of a membrane.
      • the only electron carrier not bound to a protein.
      • it can accept/donate 1 or 2 e - .
      • Cytochromes are electron carriers containing heme . Hemes in the 3 classes of cytochrome ( a , b , c ) differ in substituents on the porphyrin ring.
      • Some cytochromes(b,c1,a,a3) are part of large integral membrane protein complexes .
      • Cytochrome c is a small, water-soluble protein.
      • The heme iron can undergo 1 e - transition between ferric and ferrous states: Fe 3+ + e -  Fe 2+
      • Copper ions besides two heme groups ( a and a 3 ) act as electron carriers in Cyt a,a3
      • Cu 2+ +e -  Cu +
      Heme is a prosthetic group of cytochromes . Heme contains an iron atom in a porphyrin ring system.
      • NAD + , flavins and Q carry electrons and H +
      • Cytochromes and non-haem iron proteins carry only electrons
      • NAD +, FAD undergo only a 2 e - reaction;
      • cytochromes undergo only 1e - reactions
      • FMN, Q undergo 1e - and 2 e - reaction
      Electron carriers
    • ETC ---- REVIEW
      • a series of highly organized oxidation-reduction enzymes
      • Final common pathway in aerobic cells to transfer electrons to oxygen.
      • Inner mitochondrial mem.
      • Four complexes/ components
      • Complex I – NAD + CoQ Reductase
      • Transfer of two electrons from NADH to CoQ via FMN, coverting it into FMNH 2.
      • - FMNH2 transfers electons to Fes proteins which transfer electrons to CoQ.
      • - CoQ accepts electrons from FMNH 2
      • ( complex I ) and from FADH 2 ( complex II ) .
      • CoQ is the link between flavoproteins and cytochromes. Pumping of protons.
      • Complex II – Succinate + CoQ Reductase
      • transfer of electrons from Succinate to CoQ via FADH 2 . Succinate is converted to Fumerate during this.
      • Complex III- CoQ + Cyto. C reductase
      • Transfer of electrons from CoQH 2 to Cyt.c via Cyt.b & Cyt. c1. Fe+++ of cyt c1accepts electrons and forms Fe++ . Complex is also a proton pump.
      • Complex IV ---- Cyt.c reductase
      • Transfer of electrons from cyt c to molecular oxygen via Cyt.a , Cu++ , and Cyt.a 3 . Water is formed as a result.
      • This complex also acts as proton pump.
    • Electron Carriers NAD + or FAD There are 2 sites of entry for electrons into the electron transport chain: Both are coenzymes for dehydrogenase enzymes The transfer of electrons is not directly to oxygen but through coenzymes
    • Inhibitors of ETC
      • Site I--- complex I – Rotenone and Amytal. Inhibit electron transfer from FMN to Fes. Rotenone is used as fish poison.
      • Site II – complex III – Antimycin A, blocks electron transfer from cyt b to Fes and then cyt c1.
      • Site III – complex IV- cyanide, CO, sodium azide. Block between cyt a+a3 and oxygen.
      • When the chain is blocked, electron carriers will be in a reduced state before the block point and in an oxidized state after it.
      • This blockage eventually causes inhibition of ATP synthesis.
    • H + Transport
      • Complex I, III , IV drive H + transport from matrix to the cytosol When e - flow through , which creates p roton gradient ( electrochemical potential) across the inner membrane
      • Complex I and Complex IV : The mechanism of H + transport is still not known.
      • The mechanism of H + transport in Complex III is Q cycle.
      • 4H + are pumped per 2e  passing through complex III.
      • The H + /e  ratio is less certain for the other complexes: probably 4H + /2e  for complex I; 2H + /2e  for complex IV.
      • Q Cycle :The mechanism of H + transport in Complex III
        • Electrons are transported along the inner mitochondrial membrane, through a series of electron carriers
        • Protons (indicated by + charge) are translocated across the membrane, from the matrix to the intermembrane space
        • Oxygen is the terminal electron acceptor , combining with electrons and H + ions to produce water
        • 4. As NADH delivers more H + and electrons into the ETS, the proton gradient increases , with H + building up outside the inner mitochondrial membrane, and OH - inside the membrane.
    • Release of free energy during ETC
      • Flow of electrons is accompanied by release of free energy .
      • The electrons can be transferred as hydride ions to NAD, as hydrogen atoms to FMN, CoQ, and FAD or as electrons to cytochromes.
      • Tendency to lose electrons can be quantitatively specified by a constant Eo– standard reduction potential.
    • Reduction Potentials Number of electrons transferred in the redox reaction Faraday’s constant (96485 J/volt/mole) Crucial equation:   G o ' = -n F  E o ' The relative tendency to accept e - s and become reduced.  = E o '(acceptor) - E o '(donor) E 0 ’=standard reduction potential. If  E o ' is positive, an electron transfer reaction is spontaneous (  G o ' <0)
      • In oxidative phosphorylation, ATP is produced by the combination of ADP and Pi. Energy is obtained from the flow of electrons from NADH to molecular Oxygen during .
      • FREE ENERGY CHANGES AND SITES OF ATP FORMATION : In inner mitochondrial membrane. Three sites:-
      • - complex I - complex III - complex IV
    • Chemiosmotic hypothesis of ATP synthesis
      • Complex I,III and IV are proton pumps. Free energy of oxidation of components is coupled to the translocation of H+ from inside to outside of inner mitochondrial membrane.
      • Accumulation of protons at this site ----- electrochemical potential will drive the synthesis of ATP by activation of ATP synthase.
    • ATP synthase
      • Complex V
      • Composed of two domains --- F1 and Fo
      • Fo domain ---- spans the inner mitochondrial membrane and serves as a channel through which protons reenter into mitochondrial matrix.
      • F1 ----- extra membranous part, projects into mitochondrial matrix.
      • The protons accumulated on the cytosolic side of inner mitochondrial membrane re-enter the mitochondrail matrix through Fo. This causes rotation of Fo.
      • Rotation of Fo results in confirmational changes in F1 and result is the activation of catalytic activity of ATP synthase.
      • ADP and Pi then combine to form ATP.
    • Inhibition of Oxidative Phosphorylation
      • OLIGOMYCIN ------ binds with Fo domain,
      • - blocks H+ channels, no reentery of protons in mito. matrix. No oxid phospho.
      • ETC also stops due to accumulation of protons
      • Respiratory control ---- phosphorylation of ADP to ATP is essential for cellular respiration. Decreased level of ADP and Pi also decrease ATP synthesis.
    • Uncouplers of oxidative phosphorylation
      • These compounds uncouple ETC and Oxidative phosphorylation.
      • They increase permebility of inner mito mem to protons. 2,4 dinitrophenol is a classic example. It causes ETC to proceed at a rapid rate without forming a proton gradient. Energy is released as heat, not used for ATP. High doses of Aspirin also act as uncoupler.
      • Natural uncoupler --- brown fat.
    • Transport of ADP and ATP
      • Adenine nucleotide carrier --- transport of one molecule of ADP from cytosol into mito and exports one ATP from mito into cytosol.
      • Inhibited by plant toxin atractyloside.
    • Transport of reducing equivalents
      • NADH produced in cytosol cannot enter mito.
      • Two electrons of NADH called reducing equivalents, enter mito using shuttle mechanism.
    • CYTOPLASM OUTER MEMBRANE MATRIX INNER MEMBRANE Figure 3. The malate-aspartate shuttle. OAA Malate (1) e - NAD + e - Glu 0 (6) Glu 0 Asp -1 (4) KG KG Malate (2) e - e - OAA NADH NAD + (3) e - Complex I e - NAD + Glucose Pyruvate GLYCOLYSIS NADH Asp -1 (5)
    • CYTOPLASM INNER MEMBRANE MATRIX FAD Glycerol-3-phosphate dehydrogenase (2) DHAP OUTER MEMBRANE Figure 4. Glycerol phosphate shuttle. Cytoplasmic glycerol 3-phosphate dehydrogenase (1) oxidizes NADH. Glycerol 3-phosphate dehydrogenase in the inner membrane (2) reduces FAD to FADH 2 . G3P Dihydroxyacetone phosphate (DHAP) NAD + 3-phosphate Glycerol e  (1) FADH 2 e  CoQ e  O 2 e  NADH Glucose Pyruvate GLYCOLYSIS NAD +