Transcript of Biological oxidation -3
- 1. Chapter 7 Biological Oxidation
- 2. Biological oxidation is the cellular process in which the
organic substances release energy (ATP), produce CO2 and H2O
through oxidative-reductive reactions. organic substances:
carbohydrate, fat and protein
- 3. 7.1 Principal of Redox Reaction The electron-donating
molecule in a oxidation-reduction reaction is called the reducing
agent or reductant; the electron-accepting molecule is the
oxidizing agent or oxidant: for example: Fe2+ (ferrous) lose -e
Fe3+ (ferric) gain +e
- 4. Redox reaction = reduction-oxidation reaction Several forms
of Biological Reduction 1. Gain of electrons 2. Hydrogenation 3.
Deoxygenation Several forms of Biological Oxidation 1. Loss of
electrons 2. Dehydrogenation 3. Oxygenation
- 5. oxidation-reduction potential ( or redox potential), E : it
is a measure of the affinity of a substance for electrons. It
decide the loss (or the gain) of electrons. A positive E: the
substance has a higher affinity for electrons , accept electrons
easily. A negative E: the substance has a lower affinity for
electrons , donate electrons easily.
- 6. E0`, the standard redox potential for a substance :is
measured under stander condition(25, 1mmol/L reaction substance),at
pH7, and is expressed in volts.
- 7. Section 7.2 Respiration Chain and Oxidative
Phosphorylation
- 8. 7.2.1 Respiratory Chain Term: A chain in the mitochondria
consists of a number of redox carriers for transferring electrons
from the substrate to molecular oxygen to form oxygen ion, which
combines with protons to form water.
- 9. Redox carriers including 4 protein complexes 1.Complex I:
NADH:ubiquinone oxidoreductase NADH:CoQ oxidoreductase 2.Complex
II: Succinate dehydrogenase 3.Complex III: cytochrome bc1
(ubiquinone Cyt c oxidoreductase) 4.Complex IV: cytochrome
oxidase
- 10. Complex I ( NADH:ubiquinone oxidoreductase) Function:
transfer electrons from NADH to CoQ Components: NADH dehydrogenase
(FMN) Iron-sulfur proteins (Fe-S) complex NADH CoQ FMN; Fe-SN-1a,b;
Fe-SN-4; Fe-SN-3; Fe-SN-2
- 11. R=H: NAD+; R=H2PO3:NADP+ 1. NAD(P)+: Nicotinamide Adenine
Dinucleotide Phosphate)
- 12. Oxidation of NADH is a 2-electron(2e), 2-proton(2H)
reaction NAD+ or NADP+ NADH or NADPH
- 13. 2. FMN can transfer 1 or 2 hydride ions ach time FMN:
flavin mononucleotide Accepts 1 H+ and 1 e- Accepts 2 H + and 2 e
to form semiquinone = stable free radical to give fully reduced
form
- 14. 3. Iron-sulfur clusters (Fe-S) transfers 1electron at a
time, without proton involved Fe3++e- Fe2+
- 15. 4.Ubiquinone (CoQ) is lipid-soluble, not a component of
complex , can transfer 1 or 2 hydride ions each time. Function:
transfer electrons and protons from complex , to complex .
- 16. NADH+H+ NAD+ FMN Reduced Fe-S Q FMNH2 Oxidized Fe-S QH2
Matrix Intermembrane space
- 17. Complex II : Succinate dehydrogenase (Succinate: CoQ
oxidoreductase ) Function: transfer electrons from succinate to CoQ
Components: Succinate dehydrogenase (FAD, Fe-S) Cytochrome b560
Complex Succinate Fe-S1; b560; FAD; Fe-S2 ; Fe-S3 CoQ
- 18. Cytochromes a, b, c are heme proteins, their heme irons
participate redox reactions of e- transport. Fe3++e- Fe2+
- 19. Intermembrane space Matrix Succinate
- 20. Complex III: cytochrome bc1 (ubiquinone Cyt c
oxidoreductase) Function: transfer electrons from CoQ to cytochrome
c Components: iron-sulfur protein cytochrome b(b562, b566)
cytochrome c1 complex QH2 b562; b566; Fe-S; c1 Cyt c
- 21. Cytochrome c is soluble, which will transfer electrons to
complex Intermembrane space Matrix
- 22. Complex IV: cytochrome oxidase Function: transfer electrons
from Cyt c to molecule oxygen, the final electron acceptor.
Components: cytochrome aa3 copper ion (Cu2+) Cu2+ + e- Cu+ Complex
IV Cyt c CuAaa3CuB O2
- 23. Cytochrome c Coenzyme Q ubiquinone/ol
- 24. Sequence of respiratory chain Principles: e- tend to flow
from a redox pair with a lower Eto one with a higher E In the
e--transport chain, e--carriers are arranged in order of increasing
redox potential, making possible the gradual release of energy
stored in NADH, FADH2
- 25. Redox potential redox pair NAD+/NADH+H+ FMN/ FMNH2 FAD/
FADH2 Cyt b Fe3+/Fe2+ Q10/Q10H2 Cyt c1 Fe3+/ Fe2+ Cyt c Fe3+/Fe2+
Cyt a Fe3+ / Fe2+ Cyt a3 Fe3+ / Fe2+ 1/2 O2/ H2O E'0(V) E -0.32
-0.30 -0.06 0.040.10 0.07 0.22 0.25 0.29 0.55 0.82
- 26. There are two respiratory chains NADH respiratory chain
NADH Complex CoQ Complex cytochrome c Complex O2 Succinate (FADH2)
respiratory chain Succinate Complex CoQ Complex cytochrome c
Complex O2
- 27. NADH respiration chain FADH2 respiration chain
- 28. 7.2.2 Oxidative Phosphorylation The oxidation of organic
nutritions produces the energy-rich molecules, NADH and FADH2. The
oxidation of NADH or FADH2 in mitochondrial is the electron
transferring through respiration chain. The free energy produced in
electron transferring supports the phosphorylation of ADP to form
ATP. The oxidation of NADH or FADH2 and the formation of ATP are
coupled process, called Oxidation Phosphorylation.
- 29. The Chemiosmotic Theory The free energy of electron
transport is conserved by pumping protons from the mitochondrial
matrix to the intermembrane space so as to create an
electrochemical H+ gradient across the inner mitochondrial
membrane. The electrochemical potential of this gradient is
harnessed to synthesize ATP. Peter Mitchell
- 30. Electrochemical H+ gradient (Protonmotive force) 2
components involved 1. Chemical potential energy due to difference
in [H+] in two regions separated by a membrane 2. Electrical
potential energy that results from the separation of charge when a
proton moves across the membrane without a electron.
- 31. Complex I: 4 H+ expelled per e--pair transferred to Q
Complex III: 4 H+ expelled per e--pair transferred to Cyt c Complex
IV: 2e- + 2 H+ from matrix convert O2 to H2O; 2 further H+ expelled
from
- 32. Proton pumping: Reductiondependent conformational switch of
an e--transport complex Conformation 1 (high affinity for H+)
Conformation 2 (low affinity for H+).
- 33. ATP Synthase Intermembrane space Inner (ab2c9-12) Membrane
Matrix C ring (33 )
- 34. -subunit take up ADP and Pi to form ATP ADP + Pi ATP Each
of 3 subunits contains an active site F1: multisubunit complex that
catalyzes ATP synthesis F 0 = proton-conducting transmembrane
unit
- 35. When protons flow back through F0 channel, -subunit is
rotated by the rotation of c ring, then the conformations of
-subunits are changed, this lead to the synthesis and release of
ATP. To form a ATP need 3 protons flow into matrix. H+ flow
-subunit has three conformations:T (tight), L (loose), O
(open)
- 36. Translocation of ATP , ADP and Pi. ADP3- ATP4- H+ H2PO4- H+
Intermembrane space F0 Matrix F1 ATP4ADP3H+ H2PO4- H+
- 37. When protons flow back through F0 channel, -subunit is
rotated by the rotation of c ring, then the conformations of
-subunits are changed, this lead to the synthesis and release of
ATP. To form a ATP need 3 protons flow into matrix. H+ flow
-subunit has three conformations:T (tight), L (loose), O
(open)
- 38. P/O ratios P/O ratio is the rate of phosphate incorporated
into ATP to atoms of O2 utilized. It measure the number of ATP
molecules formed per two electrons transfer through the respiratory
chain. NADH respiratory chain : 2.5, FADH2 respiratory chain:
1.5
- 39. During two electrons transfer through NADH respiratory
chain, ten protons are pumped out of the matrix. To synthesis and
translocation an ATP, four protons are needed. So, two electrons
transport can result in 2.5 ATP. To succinate respiratory chain ,
two electrons transport can result in 1.5 ATP.
- 40. Regulation of Oxidative Phosphorylation 1.PMF (proton
motive force) regulate the electron transport. higher PMF lower
rate of transport 2.ADP concentration resting condition: energy
demanded is low, ADP concentration is low, the speed of Oxidative
Phosphorytion is low. active condition: the speed is high.
- 41. Inhibitor of Oxidative Phosphorylation 1.Inhibitor of
electron transport Succinate Antimycin A Cyanide, Azide Carbon
Monoxide Retonone Amytal
- 42. 2.Uncoupling agents uncoupling protein (in brown adipose
tissue), 2,4-dinitrophenol, Pentachlorophenol heat H+ Intermenbran
space H Cyt c uncoupling protein F0 Q F1 Matrix + H+ H+ ADP+Pi ATP
2,4-dinitrophnol
- 43. 3.Oligomycin bonds at the connection of F 0 and F1, inhibit
the function of ATP synthase. Intermembrane space Matrix Oligomycin
C ring
- 44. Succinate Retonone Amytal Antimycin A Uncoupling agent
Oligomycin
- 45. ATP and other Energy-rich compounts ATP has two energy-rich
phosphoric acid anhydride bonds, the hydrolysis of each bond
release more energy than simple phosphate esters. NH 2 N N OH OH OH
N OH OH N p O p OCH2 O O= P O OH H H H H OH OH AMP ADP ATP
- 46. Some Energy-rich compounds Structure Exemple creatine
phosphate phosphoenolpyruvate acetyl phosphate Acetyl CoA G
- 47. The hydrolysis of energy-rich bond: G = -5 -15kcal/mol The
compounds with energy-rich bond are high-energy compounds. The
hydrolysis of low-energy bond: G = -1 -3kcal/mol The compounds with
low energy bond are compounds. low-energy
- 48. Transport of high-energy bond energies 1.Substrate level
phosphorylation Glycerate 1,3-biphosphate + ADP Glycerate
3-phosphate +ATP G = -4.5kcal/mol Phosphoenolpyruvate +ADP Pyruvate
+ ATP G = -7.5kcal/mol
- 49. 2.ATP is the center of energy producing and utilizing. ATP
Oxidative Phosphorylation Energy utilization Substrate level
phosphorylation ~P ~P ADP
- 50. 3.Other nucleoside triphosphates are involved in energy
transport. GTP: gluconeogenesis protein synthesis UTP: glycogen
CTP: lipid synthesis
- 51. 4.Transport of the terminal phosphate bond of ATP to the
other nucleoside Function of nucleoside diphosphate kinase ATP +
UDP ATP + CDP ATP + GDP ADP + UTP ADP + CTP ADP + GTP Function of
adenylate kinase ADP + ADP ATP + AMP
- 52. 7.3 Energy from cytosolic NADH A mitochondrial NADH produce
2.5 ATP A cytosolic NADH must be transported into mitochondrial for
oxidation by two methods. Glycerol phosphate shuttle 1.5 ATP Malate
aspartate shuttle 2.5 ATP
- 53. Glycerol phosphate shuttle CH2OH CH2OH Electron chain
Glycerol phosphate dehydrogenase NAD+ C=O C=O CH2O- Pi NADH+H +
CH2O- Pi dihydroxyacetone phosphate dihydroxyacetone phosphate
CH2OH CH2OH CHOH CHOH CH2O- Pi CH2O- Pi Glycerol phosphate FADH2
FAD Glycerol phosphate Intermembran space Glycerol phosphate
dehydrogenase Inner menbran
- 54. Malate aspartate shuttle O Aspartate -OOC-CH2-C-COO- H 3N
Malate -ketoglutarate carrier + - - OOC-CH2-C-COO Aspartate H
oxaloacetate oxaloacetate Glutamate NADH +H+ Glutamate Electron
chain NADH +H+ NAD+ -ketoglutarate -ketoglutarate OH NAD+
-OOC-CH2-C-COOH Malate cytosol Glutamate-aspartate carrier inner
mitochondrial membran Malate matrix
- 55. 7.4 Other Biological Oxidations Monoxygenases dioxygenase
--add 2 atoms of O2 oxygenase to organic compounds. monoxygenase
(mixed-function oxidase, hydroxylase) --adds 1 oxygen atom to
organic compounds as a hydroxyl group. RH + NADPH + H+ + O2 ROH +
NADP+ + H2O
- 56. The chief compounds of monoxygenase: Cyt b5, Cyt P450, Cyt
P450 reductase(FAD,FMN)
- 57. Free Radical Scavenging Enzymes Free Radical: the groups
with an unpaired electron. (such as O2 H2O2 OH) 1.Superoxide
dismutases(SODs) 2O2 + 2H+ SOD H2O2 + O2 peroxidase H2O + O2
- 58. 2.Glutathione peroxidase H2O2 (ROOH) 2G SH NADP+
Glutathione Glutathione reductase peroxidase H2O (ROH+H2O) G S S G
NADPH+H+
- 59. 3.Catalase (in peroxisomes) 2H2O2 catalase 2H2O + O2
- 60. summary