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1、Glycogen glucoseFats fatty acids acetyl CoA CO2 Proteins amino acids NADH+ FADH2 H2O + ATP TAC stage1 stage2 stage3 Chapter 8 Biological Oxidation 所有圖片均來自互聯(lián)網(wǎng)所有圖片均來自互聯(lián)網(wǎng)Section Oxidative Respiratory Chain(Electron transfer chain) The power plant of the cell. Respiratory Chain Consists of Four Electron
2、 Transfer Complexes Complex : NADH-ubiquinone reductase Function: NADHcomplex eubiquinoneComposition: 42 kinds of peptide chains (flavoprotein, iron-sulfur protein)Prosthetic group: FMN, Fe-SFlow of Electrons: NADHFMNFe-SCoQ Fe2+ Fe3+e iron-sulfur protein (ISP)Rieske ISPv Ubiquinone (CoQ)有有 Complex
3、: Succinate-ubiquinone reductase Function: succinatecomplex eubiquinone Composition: 4 kinds of peptide chain (iron-sulfur protein, flavoprotein) Prosthetic group: Fe-S, FAD Flow of Electrons: succinate FADFe-SCoQComplex : ubiquinone-cytochrome c oxidoreductaseFunction: CoQcomplex eCyt cComposition:
4、 11 kinds of peptide chains (Cytb562,Cytb566, Cytc1, Rieske iron-sulfur protein)Prosthetic group: iron porphyrin, Fe-SFlow of Electrons: CoQCytb566(L),b562(H)Fe-S Cytc1Cytc Fe2+ Fe3+eHemeB聚異戊二烯聚異戊二烯Cytochromes are small proteins containing heme (an iron-porphyrin complex) as the prosthetic group.ubi
5、quinone-cytochrome c reductaseComplex : Cytochrome c oxidase Function: Cyt cComplexe O2Composition: 13 kinds of peptide chains (Cytaa3)Prosthetic group: iron porphyrin, 2CuFlow of Electrons: CytcCuA Cyta Cyta3 CuB O2Cytochrome c oxidase Summary of the flow of electrons and protonsthrough the four co
6、mplexes of the respiratory chain FMN:Fe-SFAD:Fe-SCyt b,c1Fe-SCoQCytcCytaa3O2H2ONADHSuccinateComplex Complex Complex Complex 1. There are two respiratory chains: NADH oxidation respiratory chain Succinate oxidation respiratory chain. NADH and FADH2 are electron donors for respiratory chain 2. Determi
7、ning the sequence of respiratory chain(1) Standard reduction potentials They arrange in order of increasing reduction potential (electrons tend to flow spontaneously from carriers of lower E0 to carriers of higher E0) (2) Specific spectrum of oxidized or reduced carriers Reducing the entire chain, b
8、ut no electron acceptor (no O2) , then O2 is suddenly introduced, each electron carrier becomes oxidized in proper order.(3) Agents that inhibit the flow of electrons through the chain are used in combination with measurement of specific spectrum of each carrier. (4) The electron carriers of the res
9、piratory chain are separated and reorganized to confirm the sequence.Section . Oxidative Phosphorylation Coupling of electron transfer and phosphorylation of ADP to ATP (ATP synthesis) in mitochondriaI.Coupling Sites of Oxidative Phosphorylation 1. P/O ratio The ratio of phosphate radicals esterifie
10、d (forming ATP from ADP) to atoms of oxygen consumed by mitochondria. (The amount of ATP produced from the movement of two electrons through a defined electron transport chain, donated by reduction of an oxygen atom. )ATPATPATPIINADHI CoQ III Cytc IV O2Substraterespiratory chainP/O ratioATP-hydroxyb
11、utyrateSuccinateAscorbic acidCytcNADI CoQ III Cytc IV O2 II CoQ III Cytc IV O2 Cytc IV O2 IV O2 2.81.70.880.6832112. Free energy change 電位差電位差 標(biāo)準(zhǔn)自由能標(biāo)準(zhǔn)自由能NADH-CoQ 0.36V -69.5 kJ /molCoQ-CytC 0.19V -36.7 kJ /molCytaa3-O2 0.58V -112 kJ /mol生成生成1摩爾摩爾ATP需能量約需能量約 30.5KJ.ATPATPATPIINADHI CoQ III Cytc IV O2
12、Chemiosmotic model (Peter Mitchell,1961)1. Oxidative phosphorylation requires an intact inner membrane, which is impermeable to protons. 2. Complex, IV functions as proton pump to establish an electrochemical gradient across the inner membrane. 3. The proton-motive force drives the synthesis of ATP
13、as protons flow back into the matrix through a proton channel associated with ATP synthase.II. Mechanism of Oxidative Phosphorylation III. ATP synthesis ATP synthase (Complex V )consists of a transmembrane proton channel (F0) and an ATPase (F1). F1 consists of 33 subunits, which contains several bin
14、ding sites for ATP and ADP, and the catalytic sites () for ATP synthesis. F0 consists of a1b2c9-12 and serves as proton channel. A model in which proton diffusion is coupled to the rotation of the c ring of the Fo complex.* Loose conformation: ADP and Pi binding * Tight conformation: ATP synthesizin
15、g* Open conformation: ATP releasingL T OT O LO L TBinding change mechanism for ATP synthesis(by Paul Boyer)3 H+ flow back 1 ATP H+ IV. The physiological roles of ATP on energy metabolismATP is the chemical link between catabolism and anabolismATPADP + Pi energyATPAMP + PPi energy 2PiATP provides ene
16、rgy by (1) hydrolysis(2) group transfer (donating a Pi, PPi or AMP to form covalent intermediates)1. ATP is a high-energy compound2. ATP is a source of phosphate energy for synthesis of the other nucleoside triphosphatesATP + NDP ADP + NTP (catalyzed by Nucleoside Diphosphokinase) ATP + UDP ADP + UT
17、P ATP + GDP ADP + GTP ATP + CDP ADP + CTPADP+ADPATP+AMP (catalyzed by adenylate kinase)3. Phosphocreatine is the storage form of energy in brain and skeletal muscleATPADPcreatinecreatineP PPOxidative phosphorylationSubstrate-level phosphorylationGlc, Fat, Pro.oxidationMuscle contrationActive Transpo
18、rtSecretionAnabolismTemperatureCTP, UTP, GTPCDP, UDP,GDPATP is the energy currency in energy metabolismI.Oxidative phosphorylation is regulated by cellular energy needs (ATP/ADP ratio) - ATP/ADP oxidative phosphorylation and citric acid cycle - ATP/ADP oxidative phosphorylation and citric acid cycle
19、 Section . The Effectors on Oxidative Phosphorylation amobarbitalFe-S of complex complex II. Inhibitors of oxidative phosphorylation 1. Inhibitors block electron transfer of respiratory chain: They inhibit not only ETC but also oxidative phosphorylation.2. Uncouplers: * dissipate the proton gradient
20、 on both side of membrane * allow electron transfer to continue without ATP synthesis. Dinitrophenol (DNP): * Hydrophobic * Picking up protons on one side and release then on the other. Uncoupling protein (UCP-1) in brown adipose tissue (BAT) produce heat: dissipate the proton gradient by forming pr
21、oton channel.3. ATP synthase inhibitors Inhibit both ETC and oxidative phosphorylationOligomycin: It blocks protons flow back to the matrix through F0 channel. III. Regulation of oxidative phosphorylation by thyroxin Induces the synthesis of Na+-K+-ATPase: ATP/ADP ratio oxidative phosphorylation Ind
22、uces gene expression of uncoupling protein:Both oxygen-consumption and heat-production Basal Metabolic Rate in patients with hyperthyroidism (甲亢) IV. Mitochondrial DNA mutation22 tRNA and 2 rRNA are encoded by mitochondrial DNA Mutations in mitochondrial DNA accumulate throughout the life of the org
23、anism. Mutations can cause a variety of human disease, which often most severely affect muscle, heart, brain.V. Transport systems of the inner mitochondrial membrane (1) Glycerolphosphate shuttle system Take place in brain and skeletal muscle 1.5 ATPs 1. Oxidation of NADH produced in cytosol Take pl
24、ace in liver and heart muscle 2.5 ATPs (2) Malate-aspartate shuttle system Adenine nucleotide and phosphate translocases2. Systems transport ADP and Pi into the matrix and ATP out to the cytosolATP-ADP translocase1. Reactive oxygen Species (ROS) are generated duringoxidative phosphorylationSection O
25、ther Oxidation/ Antioxidation SystemThese ROS can wreak havoc, reacting with and damaging enzymes, membrane lipids, and nucleic acids. Superoxide dismutases (SOD)There are 3 classes of SOD isozyme in eukaryotic cell: copper/zinc form in cytosol/extracellular (Cu/Zn-SOD) manganese form in mitochondri
26、a (Mn-SOD)2. Antioxidation system Catalase Catalase is a heme-containing enzyme that catalyzes the following reaction: 2H2O2 2H2O + O2 Catalase acts to protect against oxidative damage by H2O2. Glutathione peroxidase GPx is a Se-containing enzyme that catalyzes the following reaction: H2O2 + 2GSH 2H
27、2O + GS-SG 2GSH + R-O-OH H2O + GS-SG + R-OH2GSHNADPH+H+3. Cytochrome P450 Monooxygenase (mixed-function oxidase, or hydroxylase) in microsome Monooxygenases incorporate one atom from O2 into a product and reduce the other atom to water. RH + NADPH+H+ +O2 R-OH + NADP+ + H2O This type of enzyme is use
28、d in hydroxylation of steroid hormones, bile acid, and biotransformation in liver, etc. NADPH Monooxygenase NADPH-Cyt P450 reductase (FAD, Fe-S) Cyt P450 Respiratory chain (electron transfer chain)P/O ratioOxidative PhosphorylationKey termsRespiratory chain (electron transfer chain) The mitochondria
29、l respiratory chain consists of a series of sequentially acting electron carriers, most of which are integral proteins with prosthetic groups capable of accepting and donating either one or two electrons. Each component of the chain can accept electrons from the preceding carrier and transfer them to the following one.Oxidative phosphorylation is the process in which ATP is formed as a result of the transfer of electrons from NADH or FADH2 to O2 by a series of electron carriers. This process, which takes place in mitochondria, is the major source of ATP in aerobic organisms.
生物化學(xué)：Chapter 8 Biological Oxidation
