Energy Metabolism
Bioenergetics
--- Content provided by FirstRanker.com ---
BIOLOGICAL OXIDATIONSpecific Learning Objectives
Questions Which Wil be Answered
--- Content provided by FirstRanker.com ---
What is system of Bioenergetics ?How is chemical form of energy ATP formed (Generation)
and utilized (Operation) in human body ?
--- Content provided by FirstRanker.com ---
What Factors are associated to bioenergetics system?Metabolites
Enzymes
Coenzymes
--- Content provided by FirstRanker.com ---
CofactorsHormones
Which disorders suffered due to defective system ?
Synopsis
--- Content provided by FirstRanker.com ---
vWhat is Bioenergetics?
vHigh Energy Compounds
vSubstrate Level Phosphorylation
vWhat is Biological Oxidation?
--- Content provided by FirstRanker.com ---
vEnzymes and Coenzymes of BiologicalOxidation Reactions
vElectron Transport Chain (ETC)
--- Content provided by FirstRanker.com ---
Continued---------
vOxidative Phosphorylation Mechanism
vInhibitors of ETC and Oxidative Phosphorylation
--- Content provided by FirstRanker.com ---
vUncouplers- Mode of Action
vShuttle System
--- Content provided by FirstRanker.com ---
vFactors Involved in Oxidative Phosphorylationmechanism
--- Content provided by FirstRanker.com ---
Lets Get Introduced ToWhat Is Bioenergetics?
Bioenergetics or biochemical
--- Content provided by FirstRanker.com ---
thermodynamics is:Study of energy changes during
biochemical reactions.
--- Content provided by FirstRanker.com ---
Biological Systems Conform to General
Laws of Thermodynamics
--- Content provided by FirstRanker.com ---
Energy Is Never Destructed(Soul is energy never destructed and it is Immortal)
Total energy of a system, including its surroundings,
--- Content provided by FirstRanker.com ---
remains constant
Energy is neither lost nor gained during any change
--- Content provided by FirstRanker.com ---
May be transformed into another form of energyMay be transferred from one part of system to another
or
--- Content provided by FirstRanker.com ---
Conditions Of Bioenergetics
Isothermic (mostly)
--- Content provided by FirstRanker.com ---
Endothermic/
Endergonic/Anabolic
--- Content provided by FirstRanker.com ---
Exothermic/Exergonic/Catabolic
ENDERGONIC ( Anabolic) PROCESSES
--- Content provided by FirstRanker.com ---
PROCEED BY COUPLING
OF EXERGONIC(Catabolic)
--- Content provided by FirstRanker.com ---
PROCESSESHigh Energy Compounds Of
Human Body
--- Content provided by FirstRanker.com ---
High energy compounds are energyrich compounds.
Possess high energy bonds in its
--- Content provided by FirstRanker.com ---
structures.
Cleavage of these high energy bonds
--- Content provided by FirstRanker.com ---
liberate more energy than that ofATP hydrolysis.
S.No
--- Content provided by FirstRanker.com ---
Examples Of HighFree Energy
Energy Compounds
--- Content provided by FirstRanker.com ---
Released On
Hydrolysis.
--- Content provided by FirstRanker.com ---
Cal/mol1
Phospho Enol Pyruvate
--- Content provided by FirstRanker.com ---
-14.8
2
--- Content provided by FirstRanker.com ---
Carbamoyl Phosphate- 12.3
3
--- Content provided by FirstRanker.com ---
Cyclic AMP
-12.0
--- Content provided by FirstRanker.com ---
41,3 Bis Phospho Glycerate
-11.8
--- Content provided by FirstRanker.com ---
S.No
Examples Of High Energy
--- Content provided by FirstRanker.com ---
Free EnergyCompounds
Released On
--- Content provided by FirstRanker.com ---
Hydrolysis.
Cal/mol
--- Content provided by FirstRanker.com ---
5Creatine Phosphate
-10.3
--- Content provided by FirstRanker.com ---
6
S Adenosine Methionine
--- Content provided by FirstRanker.com ---
-10.0( SAM)
7
--- Content provided by FirstRanker.com ---
Succinyl CoA
-7.7
--- Content provided by FirstRanker.com ---
8Acetyl CoA
-7.7
--- Content provided by FirstRanker.com ---
9
ATP
--- Content provided by FirstRanker.com ---
-7.3Significance Of High Energy
--- Content provided by FirstRanker.com ---
CompoundsOR
Fates Of High Energy Compound
--- Content provided by FirstRanker.com ---
In Catabolic And Anabolic
Pathways
During Catabolic pathways/reaction
--- Content provided by FirstRanker.com ---
High energy compounds follow
--- Content provided by FirstRanker.com ---
substrate level phosphorylationreaction.
High energy compounds cleave high
--- Content provided by FirstRanker.com ---
energy bond to generate high energy
used for phosphorylation of ADP with
--- Content provided by FirstRanker.com ---
pi at reaction level.Generate ATP at substrate/reaction
level.
--- Content provided by FirstRanker.com ---
Substrate Level Phosphorylation
Mode of generation of ATP at substrate level
--- Content provided by FirstRanker.com ---
Involves cleavage of high energy bondpresent in high energy compound
Bond energy released is used for
--- Content provided by FirstRanker.com ---
Phosphorylation reaction
Generates ATP directly and instantly at
--- Content provided by FirstRanker.com ---
reaction level without involvement of ETCExamples Of High Energy
Compounds Undergoing Substrate
--- Content provided by FirstRanker.com ---
Level Phosphorylation.S.No
High Energy
--- Content provided by FirstRanker.com ---
Enzyme
Product
--- Content provided by FirstRanker.com ---
HighMetabolic
Compound
--- Content provided by FirstRanker.com ---
Catalyzing
Obtained
--- Content provided by FirstRanker.com ---
energyPathway
Phosphate
--- Content provided by FirstRanker.com ---
Involved
Compound
--- Content provided by FirstRanker.com ---
Generated1
1,3 Bis
--- Content provided by FirstRanker.com ---
Phospho
3
--- Content provided by FirstRanker.com ---
ATPGlycolysis
Phospho
--- Content provided by FirstRanker.com ---
Glycerate Phospho
Glycerate
--- Content provided by FirstRanker.com ---
KinaseGlycerate
2
--- Content provided by FirstRanker.com ---
Phospho
Pyruvate
--- Content provided by FirstRanker.com ---
EnolATP
Glycolysis
--- Content provided by FirstRanker.com ---
Enol
Kinase
--- Content provided by FirstRanker.com ---
PyruvatePyruvate
3
--- Content provided by FirstRanker.com ---
Succinyl
Succinate Succinate
--- Content provided by FirstRanker.com ---
GTPKrebs/TCA
CoA
--- Content provided by FirstRanker.com ---
Thio
Cycle
--- Content provided by FirstRanker.com ---
KinaseDuring Anabolic pathways/reaction
High energy compounds follow
--- Content provided by FirstRanker.com ---
condensation or bond buildingreactions.
High energy compound cleave to
--- Content provided by FirstRanker.com ---
generate energy
Energy used for building C-C bonds.
--- Content provided by FirstRanker.com ---
HIGH-ENERGY PHOSPHATESPLAY A CENTRAL ROLE IN ENERGY
CAPTURE AND TRANSFER
--- Content provided by FirstRanker.com ---
High Energy Compounds Generated In
Catabolic Pathways Are Utilized In
--- Content provided by FirstRanker.com ---
Anabolic Reactions
HIGH-ENERGY PHOSPHATES
--- Content provided by FirstRanker.com ---
ACT AS"ENERGY CURRENCY" OF CELL
--- Content provided by FirstRanker.com ---
Free Energy of hydrolysis Of HighEnergy Phosphate Bonds has
Important Bioenergetics
--- Content provided by FirstRanker.com ---
Significance
Adenylate Kinase (Myokinase)
--- Content provided by FirstRanker.com ---
Interconverts Adenine NucleotidesImportant Features Of ATP
Contains three high energy phosphate bonds
--- Content provided by FirstRanker.com ---
Drive endergonic reactionsIt is chemical energy currency of body
Functions in body as a complex with Mg2+
--- Content provided by FirstRanker.com ---
Biosynthesized by ATP synthase
Couples thermodynamically Unfavorable reactions to Favorable Ones
--- Content provided by FirstRanker.com ---
ATP synthesis is inhibited by UncouplersWhat Is Biological Oxidation?
Biological oxidations :
--- Content provided by FirstRanker.com ---
Oxidationreactions/Process
Occurring in living
--- Content provided by FirstRanker.com ---
cells.
Importance/Features Of
--- Content provided by FirstRanker.com ---
Biological OxidationBiological Oxidation Reactions/Process :
Involves Oxygen
--- Content provided by FirstRanker.com ---
Associated with metabolismGenerates ATP
Vital for functioning of cells
--- Content provided by FirstRanker.com ---
Survival and existence of human
body.
--- Content provided by FirstRanker.com ---
Definition Of Oxidation ReactionsOxidation reactions are
biochemical reactions where there is
--- Content provided by FirstRanker.com ---
either:Removal / Loss of Hydrogen
(Dehydrogenation)
Removal or Loss of Electrons
--- Content provided by FirstRanker.com ---
Addition of Oxygen
(Oxygenation)
Feature Of Biological Oxidation
--- Content provided by FirstRanker.com ---
Oxidation of a molecule (electron
donor) is always accompanied by
--- Content provided by FirstRanker.com ---
reduction of a second molecule(electron acceptor)
Most predominant type of
--- Content provided by FirstRanker.com ---
Oxidation reaction in bodyis:
Dehydrogenation Reaction
--- Content provided by FirstRanker.com ---
Catalyzed by Dehydrogenases
Dehydrogenases catalyzes
--- Content provided by FirstRanker.com ---
to remove Hydrogen fromsubstrates.
Which are temporarily
--- Content provided by FirstRanker.com ---
accepted by Coenzymes.
Coenzymes
and
--- Content provided by FirstRanker.com ---
Enzymes
of
--- Content provided by FirstRanker.com ---
Biological OxidationReactions
Coenzymes
--- Content provided by FirstRanker.com ---
and
Inorganic Cofactors
--- Content provided by FirstRanker.com ---
OfBiological Oxidation
Reactions
--- Content provided by FirstRanker.com ---
FMNFAD
NAD+
NADP+
THBP (Tetra Hydro Biopterin)
--- Content provided by FirstRanker.com ---
Cu++Fe+++
Oxidized Coenzymes involved in
--- Content provided by FirstRanker.com ---
Oxidation/Dehydrogenationreactions.
NAD+
--- Content provided by FirstRanker.com ---
NADP+
FAD
--- Content provided by FirstRanker.com ---
FMNOxidized Coenzymes temporarily accept
the hydrogen from substrates and get
--- Content provided by FirstRanker.com ---
transformed to reduced coenzymes.NADH+H+
FADH2
--- Content provided by FirstRanker.com ---
NADPH+H+
FMNH2
--- Content provided by FirstRanker.com ---
The reduced and oxidized forms of NADThe reduced and oxidized forms of FAD
--- Content provided by FirstRanker.com ---
5 Enzymes of Biological Oxidation1. AEROBIC
DEHYDROGENASES
--- Content provided by FirstRanker.com ---
2. ANAEROBICDEHYDROGENASES
3. OXYGENASES
--- Content provided by FirstRanker.com ---
4. OXIDASES5. HYDROPEROXIDASES
All 5 Enzymes of
--- Content provided by FirstRanker.com ---
Biological Oxidationreactions are classified
in
--- Content provided by FirstRanker.com ---
Class I
Oxido Reductases
AEROBIC DEHYDROGENASES
--- Content provided by FirstRanker.com ---
Aerobic Dehydrogenases are Flavoproteins
Enzymes covalently bound to coenzymes FMN or
FAD
--- Content provided by FirstRanker.com ---
MH2 Aerobic DH M
FMN FMNH2 (Auto
--- Content provided by FirstRanker.com ---
oxidizable)
Catalase
--- Content provided by FirstRanker.com ---
H2 +O2 H2O2 H2O + O2FMN/FAD are acceptors
of removed Hydrogen
--- Content provided by FirstRanker.com ---
Reduced Coenzymes(FMNH2/FADH2) formed
are auto oxidizable
--- Content provided by FirstRanker.com ---
Reduced coenzymes get
reoxidized at reaction
--- Content provided by FirstRanker.com ---
level.Oxygen gets directly
involved at reaction level to
--- Content provided by FirstRanker.com ---
reoxidize the reduced
coenzymes.
H2O2 is a byproduct of
--- Content provided by FirstRanker.com ---
Aerobic Dehyrogenase
activity.
--- Content provided by FirstRanker.com ---
Catalase then detoxifythe H2O2 to H2O and O2.
Specific Examples Of
--- Content provided by FirstRanker.com ---
Aerobic Dehydrogenases
L Amino acid Oxidase
(Oxidative Deamination of A.A)
--- Content provided by FirstRanker.com ---
Xanthine Oxidase(Purine Catabolism)
Glucose Oxidase
(Glucose Oxidation to Gluconic acid)
Aldehyde Dehydrogenase
--- Content provided by FirstRanker.com ---
( Alcohol Metabolism)ANAEROBIC DEHYDROGENASES
Anaerobic Dehydrogenases
--- Content provided by FirstRanker.com ---
catalyzes to removehydrogen from substrates.
With the help of coenzymes
--- Content provided by FirstRanker.com ---
NAD+/NADP+/FAD.
DEHYDROGENASES CANNOT
--- Content provided by FirstRanker.com ---
USE OXYGEN AS A HYDROGENACCEPTOR
MXH2 Anaerobic Dehydrogenase MX
--- Content provided by FirstRanker.com ---
NAD+ NADH+ H+ (Non auto oxidizable)
Enter Electron Transport Chain
--- Content provided by FirstRanker.com ---
For its reoxidationCoenzymes temporarily accept the
hydrogen from substrates and get
--- Content provided by FirstRanker.com ---
reduced toNADH+ H+
FADH2
--- Content provided by FirstRanker.com ---
NADPH+H+
FMNH2
--- Content provided by FirstRanker.com ---
Reduced coenzymes formed inAnaerobic Dehydrogenase
reactions are :
--- Content provided by FirstRanker.com ---
Non autoxidizable/not reoxidized
at reaction level.
Reduced coenzymes
--- Content provided by FirstRanker.com ---
NADH+H+ and FADH2
formed at Anaerobic
--- Content provided by FirstRanker.com ---
Dehydrogenase reactionHas to enter ETC for its
reoxidation.
--- Content provided by FirstRanker.com ---
Oxygen is involved
indirectly at an end of
--- Content provided by FirstRanker.com ---
ETC as electron andproton acceptor .
Metabolic water is an
--- Content provided by FirstRanker.com ---
end product of ETC.
Remember
Reduced coenzyme NADPH+H+
--- Content provided by FirstRanker.com ---
do not enter ETC
NADPH+H+ is utilized as
--- Content provided by FirstRanker.com ---
reducing equivalent forreduction reactions catalyzed
by Reductases.
--- Content provided by FirstRanker.com ---
NAD+ Dependent Anaerobic Dehydrogenases
Enzymes
--- Content provided by FirstRanker.com ---
Pathway /ReactionGlyceraldehyde -3-PO4
Glycolysis
--- Content provided by FirstRanker.com ---
Dehydrogenase
Pyruvate Dehydrogenase
--- Content provided by FirstRanker.com ---
PDH ComplexIsocitrate Dehydrogenase
TCA cycle
--- Content provided by FirstRanker.com ---
Ketoglutarate Dehydrogenase
TCA cycle
--- Content provided by FirstRanker.com ---
Malate DehydrogenaseTCA cycle
Lactate Dehydrogenase
--- Content provided by FirstRanker.com ---
Pyruvate/Lactate metabolism
Glutamate Dehydrogenase
--- Content provided by FirstRanker.com ---
Glutamate metabolismHydroxy Acyl Dehydrogenase
Beta Oxidation of Fatty acids
--- Content provided by FirstRanker.com ---
NADP+ DependentDehydrogenases
Glucose -6-Phosphate Dehydrogenase
--- Content provided by FirstRanker.com ---
( HMP Shunt)
Phospho Gluconate Dehydrogenase
--- Content provided by FirstRanker.com ---
(HMP Shunt)Note NADPH+H+does not enter ETC for
its reoxidation instead they are involved in
--- Content provided by FirstRanker.com ---
reduction reactions.
FAD Dependent Anaerobic
--- Content provided by FirstRanker.com ---
DehydrogenasesSuccinate Dehydrogenase
(TCA Cycle)
Acyl CoA Dehydrogenase
--- Content provided by FirstRanker.com ---
( Oxidation Of Fatty Acids)FMN Dependent Anaerobic
Dehydrogenase
--- Content provided by FirstRanker.com ---
NADH Dehydrogenase(Warburg's Yellow
Enzyme)
--- Content provided by FirstRanker.com ---
First Component of ETC/
Complex I of ETC
--- Content provided by FirstRanker.com ---
OXYGENASESOxygenases add Oxygen
atom from molecular oxygen
--- Content provided by FirstRanker.com ---
(O2) into substrate.
Form Oxidized Products
OXYGENASES CATALYZE
--- Content provided by FirstRanker.com ---
DIRECT TRANSFER AND
INCORPORATION OF OXYGEN
--- Content provided by FirstRanker.com ---
INTO A SUBSTRATE MOLECULEMono Oxygenases
Mono Oxygenases add one oxygen
--- Content provided by FirstRanker.com ---
atom from molecular oxygen to the
substrate.
--- Content provided by FirstRanker.com ---
Forms Hydroxyl group (-OH )Monoxygenases are also termed as
Hydroxylases or Mixed Function
--- Content provided by FirstRanker.com ---
Oxidase.AH + O2+BH2 Mono Oxygenase AOH+ B+H2O
Tyrosine+O2+THBP Tyrosine
--- Content provided by FirstRanker.com ---
DOPA+DHBP+H2OHydroxylase
Examples Of Mono Oxygenases
--- Content provided by FirstRanker.com ---
Phenylalanine Hydroxylase
(Phenylalanine to Tyrosine)
Tryptophan Hydroxylase
(Tryptophan to 5HydroxyTryptophan)
--- Content provided by FirstRanker.com ---
25 Hydroxylase(Vitamin D - Cholecalciferol activation)
1 Hydroxylase
(Vitamin D - Cholecalciferol activation)
Di Oxygenases
--- Content provided by FirstRanker.com ---
Dioxygenases are true Oxygenases
Incorporates two Oxygen atoms
from O2.
--- Content provided by FirstRanker.com ---
A+ O2 Dioxygenase AO2
Examples Of Dioxygenases
--- Content provided by FirstRanker.com ---
Tryptophan Di Oxygenase/Tryptophan Pyrrolase
(Tryptophan NFormyl Kynurenine )
--- Content provided by FirstRanker.com ---
PHPP DioxygenaseCysteine Dioxygenase
Homogentisate Oxidase
(Homogentisate to 4 Maleyl Acetoacetate)
--- Content provided by FirstRanker.com ---
Cytochromes P450
--- Content provided by FirstRanker.com ---
Are Monooxygenases
Important in Steroid Metabolism
--- Content provided by FirstRanker.com ---
& forDetoxification of Many Drugs
Oxidases
--- Content provided by FirstRanker.com ---
Oxidases involve activatedmolecular Oxygen as
Hydrogen (electron and proton )
--- Content provided by FirstRanker.com ---
acceptor.
Oxidases Reduce Oxygen to
--- Content provided by FirstRanker.com ---
form Water (H2O)OXIDASES USE OXYGEN
AS A HYDROGEN ACCEPTOR
--- Content provided by FirstRanker.com ---
AH2 + ? O2 Oxidase A+ H2O
Tyrosine+ O2 Tyrosinase -Cu++ DOPA +
--- Content provided by FirstRanker.com ---
H2OExamples Of Oxidases
Cytochrome Oxidase-Classic Example
--- Content provided by FirstRanker.com ---
(Hemoprotein ETC enzyme)Ascorbate Oxidase
Mono Amine Oxidase
Catechol Oxidase
--- Content provided by FirstRanker.com ---
HYDROPEROXIDASES USE HYDROGEN PEROXIDE
OR AN ORGANIC PEROXIDE AS SUBSTRATE
--- Content provided by FirstRanker.com ---
Hydroperoxidases detoxifyHydrogen Peroxide in body.
H2O2 is a substrate/reactant
--- Content provided by FirstRanker.com ---
for Hydroperoxidases.
Hydroperoxidases are
Hemoproteins.
--- Content provided by FirstRanker.com ---
Contains loosely bound
Heme as prosthetic
--- Content provided by FirstRanker.com ---
group.Hydroperoxidases prevent
accumulation of H2O2 in cells.
--- Content provided by FirstRanker.com ---
H2O2 if accumulated in cells is
toxic
--- Content provided by FirstRanker.com ---
Leads to disruption ofmembranes(Hemolysis).
Increases risk of cancer and
--- Content provided by FirstRanker.com ---
atherosclerosis.
Specific Examples Of
Hydroperoxidases
--- Content provided by FirstRanker.com ---
Peroxidases
Catalase
Peroxidases Reduce Peroxides Using Various
--- Content provided by FirstRanker.com ---
Electron Acceptors
Indirectly react with H2O2
--- Content provided by FirstRanker.com ---
Glutathione Peroxidase(In R.B.C's)
Leukocyte Peroxidase
(In W.B.C's)
--- Content provided by FirstRanker.com ---
H2O2 + 2 GSH Glutathione Peroxidase 2H2O + GSSG
(Reduced (Oxidized
active Form)
--- Content provided by FirstRanker.com ---
inactive Form)
--- Content provided by FirstRanker.com ---
CatalaseDirectly reacts with H2O2.
Associated with Aerobic
--- Content provided by FirstRanker.com ---
Dehydrogenase catalyzedreaction.
2H2O2 Catalase 2H2O +O2
--- Content provided by FirstRanker.com ---
Biological Oxidation ProcessElectron Transport Chain
(ETC)
--- Content provided by FirstRanker.com ---
Oxidative Phosphorylation
Synonyms Of ETC
1. Electron Transport Chain (ETC)
--- Content provided by FirstRanker.com ---
2. Oxidative Phosphorylation3. Electron Transport System (ETS)
4. Fate of Reduced Coenzymes of
FADH2 and NADH+H+
--- Content provided by FirstRanker.com ---
5. Respiratory Chain
6. Internal/Cellular Respiration
7. Tertiary metabolism
8. Final Oxidative Pathway
--- Content provided by FirstRanker.com ---
What is Electron Transport Chain?
Electron Transport chain
Biological oxidation process very vital for human
--- Content provided by FirstRanker.com ---
being survival
Truly Aerobic in nature(indispensable on O2)
--- Content provided by FirstRanker.com ---
Located and operated at inner membrane ofMitochondria
Alternate Oxidation and Reduction Reactions
--- Content provided by FirstRanker.com ---
carried out in process
What is Oxidative Phosphorylation?
--- Content provided by FirstRanker.com ---
Oxidation process (ETC) is tightly
coupled with Phosphorylation of
--- Content provided by FirstRanker.com ---
ADP with pi to generate ATP.Illustrated as Sun and Day Light
Oxidative
--- Content provided by FirstRanker.com ---
Phosphorylation is a
major mode of ATP
--- Content provided by FirstRanker.com ---
generation inhuman body
What is Fate of ETC/
--- Content provided by FirstRanker.com ---
Oxidative Phosphorylation ?REOXIDIZES
REDUCING EQUIVALENTS
--- Content provided by FirstRanker.com ---
(NADH+ H+ and FADH2)
GENERATED DURING ANAEROBIC
--- Content provided by FirstRanker.com ---
DEHYDROGENASE REACTIONElectron Transport Chain
On Operation
--- Content provided by FirstRanker.com ---
Transports Electrons and ProtonsThrough series of ETC components
Finally H2 is received by activated
--- Content provided by FirstRanker.com ---
molecular Oxygen (1/2 O2)
Generates significant byproduct ATP
--- Content provided by FirstRanker.com ---
and metabolic water at end of processCondition In which ETC Operates
ETC operates in truly aerobic
--- Content provided by FirstRanker.com ---
condition.
Oxygen unloaded at cellular
--- Content provided by FirstRanker.com ---
level by HbO2Gets utilized at an end of ETC
process. (Respiratory Chain)
--- Content provided by FirstRanker.com ---
Site OfElectron Transport Chain
OR
--- Content provided by FirstRanker.com ---
Oxidative Phosphorylation
ETC is located and operated
--- Content provided by FirstRanker.com ---
in all cells which containMitochondria (Power house
of Cell)
--- Content provided by FirstRanker.com ---
(Except mature Erythrocytes which are
devoid of mitochondria)
--- Content provided by FirstRanker.com ---
Location of Mitochondrial ETC Complexes
? Inner membrane of Mitochondria
--- Content provided by FirstRanker.com ---
? Rich In CardiolipinComponents and Enzymes of ETC
are arranged towards inner
--- Content provided by FirstRanker.com ---
surface of inner membrane of
mitochondria as:
--- Content provided by FirstRanker.com ---
Vectorial conformationIncreased order of positive redox
potential
--- Content provided by FirstRanker.com ---
Number of Mitochondria Vary inDifferent cells
Number of Mitochondria changes
--- Content provided by FirstRanker.com ---
from cell to cell , tissue to tissue,
organ to organ, organism to
--- Content provided by FirstRanker.com ---
organismFactors Responsible For Number of
Mitochondria in Cell
--- Content provided by FirstRanker.com ---
Type of cell, organ and itsfunction
Metabolic status of an individual
--- Content provided by FirstRanker.com ---
Physical activity of an individual
How much energy cell needs to
--- Content provided by FirstRanker.com ---
produce?High number of Mitochondria present in
Heart, Rod cells, Sperm,
--- Content provided by FirstRanker.com ---
ciliated cells
Muscle cells for example, contain more
--- Content provided by FirstRanker.com ---
number of mitochondria compared toKidney cells.
Marathon runners have more number of
--- Content provided by FirstRanker.com ---
mitochondria in their leg muscle cells than
people with desk jobs
Components Of ETC
--- Content provided by FirstRanker.com ---
Series Of Protein Complexes
Flavoproteins & Iron-Sulfur
--- Content provided by FirstRanker.com ---
Proteins (Fe-S),Cytochromesare Components
of Respiratory Chain Complexes
--- Content provided by FirstRanker.com ---
1.Flavo Protein- (First Component)
NADH Dehydrogenase-FMN and FeS
--- Content provided by FirstRanker.com ---
centers(Warburg's Yellow Enzyme)2. Coenzyme Q/ Ubiquinone
3. Series of Cytochromes-
--- Content provided by FirstRanker.com ---
Cytochrome b-Cytochrome c1-Cytochrome c- Cytochrome aa3
Coenzyme Q / Ubiquinone
--- Content provided by FirstRanker.com ---
Coenzyme Q (CoQ)/ Ubiquinone)
is located in lipid core of
--- Content provided by FirstRanker.com ---
mitochondrial membrane.It is a Quinone derivative
Lipophilic dissolves in
--- Content provided by FirstRanker.com ---
hydrocarbon core of a membrane.Coenzyme Q is very
hydrophobic.
Coenzyme Q has a long Poly
--- Content provided by FirstRanker.com ---
isoprenoid tail, with multiple
units of isoprene.
--- Content provided by FirstRanker.com ---
In human cells, most often n = 10Q10 isoprenoid tail is longer than
width of a bilayer.
--- Content provided by FirstRanker.com ---
Coenzyme Q functions as a
mobile e- carrier within
--- Content provided by FirstRanker.com ---
mitochondrial innermembrane.
Its role in trans-membrane H+
--- Content provided by FirstRanker.com ---
transport coupled to e-
transfer (Q Cycle).
Coenzyme Q
--- Content provided by FirstRanker.com ---
Accepts
Both Protons and Electrons
--- Content provided by FirstRanker.com ---
Quinone ring ofcoenzyme Q can
be reduced to
--- Content provided by FirstRanker.com ---
Quinol in a 2e-
reaction:
--- Content provided by FirstRanker.com ---
Q + 2 e- + 2 H+ QH .2
When bound to special sites in respiratory complexes,
--- Content provided by FirstRanker.com ---
CoQ can accept 1 e- to form a semiquinone radical (Q?-).
Thus CoQ, like FMN, can mediate between 1 e- & 2 e-
--- Content provided by FirstRanker.com ---
donors/acceptors.
Cytochromes
--- Content provided by FirstRanker.com ---
Cytochromes are Hemoproteins
conjugated proteins in ETC
--- Content provided by FirstRanker.com ---
Carrier of electrons
Contain heme as prosthetic group
--- Content provided by FirstRanker.com ---
Cytochrome Heme
--- Content provided by FirstRanker.com ---
Cytochrome Heme Iron is intransitional state
Carries only electrons
--- Content provided by FirstRanker.com ---
Fe (III) + e- Fe (II)Only one electron is transferred at
a time.
Cytochrome heme iron
--- Content provided by FirstRanker.com ---
can undergo 1 e-
transition between ferric
--- Content provided by FirstRanker.com ---
and ferrous states:Fe+++ + e- Fe++
(oxidized) (reduced)
--- Content provided by FirstRanker.com ---
Cytochromes May Also BeRegarded as Dehydrogenases
Series of Cytochromes b, c , c, aa
--- Content provided by FirstRanker.com ---
1
3
--- Content provided by FirstRanker.com ---
relay electrons (one at a time, in thisorder
Cytochrome c is a small,
--- Content provided by FirstRanker.com ---
water soluble protein with asingle heme group.
Cytochromes a & a3 are
--- Content provided by FirstRanker.com ---
often referred to as
Cytochrome Oxidase
--- Content provided by FirstRanker.com ---
/complex IVCytochrome aa3 has Fe and
Cu.
--- Content provided by FirstRanker.com ---
All Cytochromesexcept Cytochrome
Oxidase are Anaerobic
--- Content provided by FirstRanker.com ---
Dehydrogenase
activity.
--- Content provided by FirstRanker.com ---
Cytochromes absorb light atcharacteristic wavelengths.
Absorbance changes upon
--- Content provided by FirstRanker.com ---
oxidation/reduction of
Heme Iron
Components of Respiratory Chain
--- Content provided by FirstRanker.com ---
are Contained in
Protein Complexes Embedded in
--- Content provided by FirstRanker.com ---
Inner Mitochondrial MembraneFive Complexes of
Oxidative Phosphorylation
--- Content provided by FirstRanker.com ---
Complexes of OxidativePhosphorylation
There exists 5 complexes
--- Content provided by FirstRanker.com ---
Processing Oxidative
Phosphorylation to generate
--- Content provided by FirstRanker.com ---
ATPComplexes are combination of one
or two components
--- Content provided by FirstRanker.com ---
Complex I- NADH CoQ Reductase
NADH Dehydrogenase FMN and FeS centre
Complex II ? Succinate CoQ Reductase
Succinate Dehydrogenase FAD and FeS centre
--- Content provided by FirstRanker.com ---
Complex III?CoQ Cytochrome C ReductaseCytochrome b ? Cytochrome c1
Complex IV- Cytochrome Oxidase
Cytochrome aa3
Complex V ? ATP Synthetase
--- Content provided by FirstRanker.com ---
F0 and F1 of ATP SynthaseComposition of Oxidative Phosphorylation Complexes
No. of
--- Content provided by FirstRanker.com ---
Prosthetic GroupsComplex
Name
--- Content provided by FirstRanker.com ---
Proteins
Complex I
--- Content provided by FirstRanker.com ---
NADH ?CoQ46
FMN,
--- Content provided by FirstRanker.com ---
Reductase
9 Fe-S centers
--- Content provided by FirstRanker.com ---
Complex IISuccinate-CoQ
5
--- Content provided by FirstRanker.com ---
FAD, cyt b ,
560
--- Content provided by FirstRanker.com ---
Reductase3 Fe-S centrs.
Complex III
--- Content provided by FirstRanker.com ---
CoQ-cyt c Reductase
11
--- Content provided by FirstRanker.com ---
cyt b , cyt b , cyt c ,H
L
--- Content provided by FirstRanker.com ---
1
Fe-SRieske
--- Content provided by FirstRanker.com ---
Complex IVCytochrome Oxidase
13
--- Content provided by FirstRanker.com ---
cyt a, cyt a , Cu , Cu
3
--- Content provided by FirstRanker.com ---
AB
ETC Components Associated With
--- Content provided by FirstRanker.com ---
Multiple Iron Sulfur Centers
Iron exists in Transitional State
--- Content provided by FirstRanker.com ---
Responsible for Oxidation andReduction Reactions
Complex I,I and II contains Iron
--- Content provided by FirstRanker.com ---
Sulfur CentersComplex IV and V do not Contain
Iron Sulfur Centers
--- Content provided by FirstRanker.com ---
ETC Components
With Iron Sulfur Centers
--- Content provided by FirstRanker.com ---
NADH DehydrogenaseCoenzyme Q-Cytochrome Reductase
Succinate ?Coenzyme Q Reductase
--- Content provided by FirstRanker.com ---
Iron-sulfur centers (Fe-S) are prosthetic groupscontaining 2, 3 , 4 or 8 iron atoms complexed to elemental
& Cysteine S.
--- Content provided by FirstRanker.com ---
4-Fe centers have a tetrahedral structure, with Fe & Satoms alternating as vertices of a cube.
Cysteine residues provide S ligands to the iron, while also
--- Content provided by FirstRanker.com ---
holding these prosthetic groups in place within the protein.Electron transfer proteins
may contain multiple Fe-S
--- Content provided by FirstRanker.com ---
centers.
Iron-sulfur centers
transfer only one
--- Content provided by FirstRanker.com ---
electron, even if they
contain two or more iron
--- Content provided by FirstRanker.com ---
atoms, because of closeproximity of iron atoms.
Fe+++ (oxidized) + 1 e- Fe++ (reduced)
--- Content provided by FirstRanker.com ---
COMPLEX IV
Cytochrome a-a3/ Cytochrome Oxidase
--- Content provided by FirstRanker.com ---
large proteinBoth a and a3 contain heme and Cu
Does not contain Fe ?S clusters
a3 Cu binds to oxygen and donates
--- Content provided by FirstRanker.com ---
electrons to oxygenCytochrome a3 - only component of
ETC that can interact with O2
--- Content provided by FirstRanker.com ---
Cytochrome Oxidase (complex IV) carries outfollowing irreversible reaction:
O + 4
--- Content provided by FirstRanker.com ---
O2
H+ + 4 e- 2 H2
--- Content provided by FirstRanker.com ---
Four electrons are transferred into complex one at
a time from Cytochrome c.
Complex IV/Cytochrome
--- Content provided by FirstRanker.com ---
Oxidase reduces molecular
Oxygen to water.
--- Content provided by FirstRanker.com ---
Cytochrome OxidaseCu(II) Cu(I)
e- from cyt c to a
--- Content provided by FirstRanker.com ---
Heme A and Cu act together to
transfer electrons to oxygen
Metal centers of cytochrome oxidase (complex IV):
--- Content provided by FirstRanker.com ---
heme a & heme a3,CuA (2 adjacent Cu atoms) & CuB.
O2 reacts at a binuclear center consisting of heme
--- Content provided by FirstRanker.com ---
a and Cu .3
B
--- Content provided by FirstRanker.com ---
An Iron-Copper Center
in Cytochrome Oxidase
--- Content provided by FirstRanker.com ---
Catalyzes Efficient O2Reduction
--- Content provided by FirstRanker.com ---
Complex VATP Synthase
Two units, Fo and F1
--- Content provided by FirstRanker.com ---
("knob-and-stalk"; "bal on a stick")
F1 contains the catalytic subunits
--- Content provided by FirstRanker.com ---
where ADP and Pi are broughttogether for combination.
F0 spans the membrane and serves as
--- Content provided by FirstRanker.com ---
a proton channel.
? F1 contains 5 types of
--- Content provided by FirstRanker.com ---
polypeptide chains - a3b3gde? Fo - a1b2c10-14
(c subunits form cylindrical,
--- Content provided by FirstRanker.com ---
membrane-bound base)
? Fo and F1 are connected by a
--- Content provided by FirstRanker.com ---
ge stalk and by exteriorcolumn (a1b2 and d)
? Proton channel is ? between c
--- Content provided by FirstRanker.com ---
ring and a subunit.
Complex V ATP Synthase
--- Content provided by FirstRanker.com ---
How do ATPase and ATP Synthase
Differ?
--- Content provided by FirstRanker.com ---
ATPase is an enzyme thathydrolyze ATP to form ADP
ATP synthase synthesize ATP
--- Content provided by FirstRanker.com ---
Both enzyme found in mitochondria
F- ATPase/ATP Synthase
--- Content provided by FirstRanker.com ---
F-ATPase belong to
superfamily of related ATP
--- Content provided by FirstRanker.com ---
SynthasesF-ATPase is a Rotating Motor
Mechanism Of Oxidative
--- Content provided by FirstRanker.com ---
PhosphorylationSalient Features/Required Criteria's
Of
--- Content provided by FirstRanker.com ---
ETC/Oxidative Phosphorylation
OR
--- Content provided by FirstRanker.com ---
Criteria's Required For OxidativePhosphorylation
1
--- Content provided by FirstRanker.com ---
Arrangement OfElectron Transport Chain
Components In Increased Order
--- Content provided by FirstRanker.com ---
Of Positive Redox Potential
Redox Potentials & Redox Couples
FREE ENERGY
--- Content provided by FirstRanker.com ---
CHANGES CAN BE
EXPRESSED IN TERMS
--- Content provided by FirstRanker.com ---
OF REDOX POTENTIALRedox Potential is a
measure of tendency of a
--- Content provided by FirstRanker.com ---
redox couple to accept or
donate electrons under
--- Content provided by FirstRanker.com ---
standard condition.Components that have most negative
redox potentials
--- Content provided by FirstRanker.com ---
Have weakest affinity for electronsHence has capacity to donate its
electrons.
--- Content provided by FirstRanker.com ---
Redox couple with most positive
redox potentials have
--- Content provided by FirstRanker.com ---
Strongest affinity for electrons
therefore
--- Content provided by FirstRanker.com ---
Possess strongest tendency toaccept electrons.
During E.T.C there is transfer
--- Content provided by FirstRanker.com ---
of reducing equivalentsFrom low redox potential
to high redox potential.
--- Content provided by FirstRanker.com ---
This exhibit free energy
change there by liberating
--- Content provided by FirstRanker.com ---
heat energyElectrons move spontaneously from
one component of ETC to another
--- Content provided by FirstRanker.com ---
with a
low redox potential (a low affinity
--- Content provided by FirstRanker.com ---
for electrons) to a component with ahigh redox potential (a high
affinity for electrons)
--- Content provided by FirstRanker.com ---
In ETC electrons move from acarrier with
Low redox potential
--- Content provided by FirstRanker.com ---
(high tendency to donate
electrons) toward carriers
--- Content provided by FirstRanker.com ---
Higher redox potential
(high tendency to accept
--- Content provided by FirstRanker.com ---
electrons)Redox Couple
Components of ETC has capacity
--- Content provided by FirstRanker.com ---
to exist in oxidant and reduced
forms.
--- Content provided by FirstRanker.com ---
This pair is known as redoxcouple
CoQ/CoQH2
--- Content provided by FirstRanker.com ---
Cyt b Fe+++/Cyt b Fe++Sequence of
--- Content provided by FirstRanker.com ---
RespiratoryElectron
Carriers
--- Content provided by FirstRanker.com ---
Inhibitors
in green
--- Content provided by FirstRanker.com ---
2Development Of
Proton Gradient And Proton Motive Force
--- Content provided by FirstRanker.com ---
In Intermembrane Space
Complex I,I I and IV
--- Content provided by FirstRanker.com ---
Pumps Protons From Matrix side
to Intermembrane Space
--- Content provided by FirstRanker.com ---
and generatesProton Motive Force
--- Content provided by FirstRanker.com ---
Complex I,I I and IVServe as Proton Channels
Complex I ,III and IV act as a
--- Content provided by FirstRanker.com ---
Proton Pump.
Pump out protons from matrix
--- Content provided by FirstRanker.com ---
side to inter membrane space ofmitochondria.
Develop a proton gradient in
--- Content provided by FirstRanker.com ---
inter membrane space.
This supports the mechanism of
--- Content provided by FirstRanker.com ---
Oxidative Phosphorylation.A Large Drop in Redox
--- Content provided by FirstRanker.com ---
Potential across each of thethree Respiratory Enzyme
Complexes (I,III,IV).
--- Content provided by FirstRanker.com ---
Provides the Energy for H+
Pumping
--- Content provided by FirstRanker.com ---
3
Free Energy Change Occurs
--- Content provided by FirstRanker.com ---
Due To Transport OF ProtonPumping and Electron Exchange
During Oxidative Phosphorylation
--- Content provided by FirstRanker.com ---
4Heat Energy Generated At Certain
Specific Sites During Oxidation
--- Content provided by FirstRanker.com ---
Is Transformed By Chemical
Phosphorylation Reaction of ADP
--- Content provided by FirstRanker.com ---
and pi to form ATP5
ATP Synthase /Complex V
--- Content provided by FirstRanker.com ---
Activation for Phosphorylation
Reaction
Proton gradient runs
--- Content provided by FirstRanker.com ---
downhill through ATP
Synthase to drive
--- Content provided by FirstRanker.com ---
synthesis of ATPqF F of ATP Synthase catalyzes
1 o
--- Content provided by FirstRanker.com ---
phosphorylation reaction for ATPsynthesis
q Transport of H+ from intermembrane
--- Content provided by FirstRanker.com ---
space to into the mitochondrial matrix
through ATP Synthase is mandatory.
--- Content provided by FirstRanker.com ---
qTransport of at least 3 H+ per ATP isrequired through ATP Synthase for its
activation and catalysis.
--- Content provided by FirstRanker.com ---
Thus heat energy is
transformed to
--- Content provided by FirstRanker.com ---
chemical form ofenergy (ATP) in
Oxidative
--- Content provided by FirstRanker.com ---
Phosphorylation.
6
Oxygen is Terminal Acceptor of
--- Content provided by FirstRanker.com ---
Protons and electrons During
Oxidative Phosphorylation To
--- Content provided by FirstRanker.com ---
Generate Metabolic WaterOxygen has highest (most
positive) standard redox
--- Content provided by FirstRanker.com ---
potential
Most likely to accept electrons
--- Content provided by FirstRanker.com ---
from other carriers.Electrons ultimately reduce Oxygen
to water (metabolic water)
--- Content provided by FirstRanker.com ---
2 H+ + 2 e- + ? O2 -- H2OAt end of E.T.C by catalytic activity of
Cytochrome Oxidase
--- Content provided by FirstRanker.com ---
Protons released at Coenzyme Q and
electrons transported by Cytochromes
--- Content provided by FirstRanker.com ---
are
Accepted by activated molecular
--- Content provided by FirstRanker.com ---
oxygen (1/2 O2) to form metabolicwater.
--- Content provided by FirstRanker.com ---
Cytochrome oxidasecontrols rate of O2
uptake which
--- Content provided by FirstRanker.com ---
Means this enzyme
determines how
--- Content provided by FirstRanker.com ---
rapidly we breathe.Respired Oxygen
transported by Hb
--- Content provided by FirstRanker.com ---
unloaded at tissue/
cellular level is
--- Content provided by FirstRanker.com ---
utilized during E.T.C.7
Coenzyme Q Accepts Electrons
--- Content provided by FirstRanker.com ---
Via Complexes I & IIPoint To Note
In ETC electrons flow from
Most electro negative potential
--- Content provided by FirstRanker.com ---
NADH+H+ (-0.32) to most
electro positive potential
--- Content provided by FirstRanker.com ---
(+0.82) ? O2 .HOW
ETC /Oxidative
--- Content provided by FirstRanker.com ---
Phosphorylation Operates ?
Most Oxidative
--- Content provided by FirstRanker.com ---
Metabolic Pathways
(TCA and Beta Oxidation Of Fatty acids)
--- Content provided by FirstRanker.com ---
Located In Mitochondrial MatrixGenerate Reduced Coenzymes
Reduced coenzymes
--- Content provided by FirstRanker.com ---
NADH+H+/FADH2Generated during Anaerobic
Dehydrogenase reactions of
--- Content provided by FirstRanker.com ---
Carbohydrates, Lipids metabolic
pathways.
--- Content provided by FirstRanker.com ---
Get reoxidized on entering E.T.CReduced coenzymes NADH+H+ and
FADH2 are formed in Mitochondrial
--- Content provided by FirstRanker.com ---
matrix:
Oxidative Decarboxylation of
--- Content provided by FirstRanker.com ---
Pyruvate to Acetyl CoA by PDHcomplex.
Oxidation of Acetyl CoA by TCA cycle
--- Content provided by FirstRanker.com ---
Beta Oxidation of fatty acids
NADH+H+ and FADH2 are
energy rich molecules
--- Content provided by FirstRanker.com ---
Contains a pair of
electrons having a high
--- Content provided by FirstRanker.com ---
transfer potential.
Entry Of NADH+H+ in ETC
--- Content provided by FirstRanker.com ---
When NADH+H+ enters ETC reducingequivalents Protons and Electrons are
taken up by first component
--- Content provided by FirstRanker.com ---
/Complex I (Flavoproteins)
Then from complex I the reducing
--- Content provided by FirstRanker.com ---
equivalents are transferred to CoQ.Entry Of FADH2 in ETC
FADH2 is generated at Succinate
--- Content provided by FirstRanker.com ---
Dehydrogenase reaction(Complex II)FADH2 enters ETC process and its
reducing equivalents are taken up by
--- Content provided by FirstRanker.com ---
CoQ .
CoQH2 then here onwards transfers
--- Content provided by FirstRanker.com ---
only electrons to series of arrangedCytochromes and Protons are
released in matrix.
--- Content provided by FirstRanker.com ---
ELECTRON TRANSPORT CHAIN
Series of enzyme complexes (electron carriers)
--- Content provided by FirstRanker.com ---
embedded in the inner mitochondrial membrane, which
oxidize NADH+H+ and FADH2 and transport electrons to
--- Content provided by FirstRanker.com ---
oxygen is cal ed Respiratory Electron-Transport Chain(ETC).
Sequence of Electron Carriers in ETC
--- Content provided by FirstRanker.com ---
NADH FMN-Fe-S Co-Q Fe cyt b
cyt c1 cyt c cyt a cyt a3 O2
--- Content provided by FirstRanker.com ---
Succinate FAD Fe-S
--- Content provided by FirstRanker.com ---
Electrons of NADH or FADH2 are used toreduce molecular oxygen to water.
A large amount of free energy is liberated.
--- Content provided by FirstRanker.com ---
The electrons from NADH+H+ and FADH2 are not
transported directly to O2 but are transferred
--- Content provided by FirstRanker.com ---
through series of electron carriers that undergoreversible reduction and oxidation.
ETC Process
--- Content provided by FirstRanker.com ---
A PROTON GRADIENT POWERS THESYNTHESIS OF ATP
Transport of electrons from NADH or FADH2 to O2 via the
--- Content provided by FirstRanker.com ---
electron-transport chain is exergonic process:
NADH + ?O2 + H+ H2O + NAD+
FADH2 + ?O2 H2O + FAD+
Go' = -52.6 kcal/mol for NADH
--- Content provided by FirstRanker.com ---
-36.3 kcal/mol for FADH2This process is coupled to the synthesis of ATP (endergonic
process)
--- Content provided by FirstRanker.com ---
ADP + Pi ATP + H2O Go'=+7.3 kcal/molIn E.T.C both Protons and Electrons
are transferred up to Coenzyme Q
--- Content provided by FirstRanker.com ---
level.At coenzyme Q level protons (2H+)are
released in the medium.
--- Content provided by FirstRanker.com ---
From Coenzyme Q onwards only
electrons are transferred through a
--- Content provided by FirstRanker.com ---
series of Cytochromes in E.T.C.Electrons get transfer through
series of Cytochromes
--- Content provided by FirstRanker.com ---
Cytochrome Fe is in transitional
state (Ferric/Ferrous ).
In E.T.C there are
--- Content provided by FirstRanker.com ---
alternate reduction
and oxidation
--- Content provided by FirstRanker.com ---
reactions.Flow of electrons through ETC
complexes leads to pumping of
--- Content provided by FirstRanker.com ---
protons out of the mitochondrial
matrix in intermembrane space.
--- Content provided by FirstRanker.com ---
This accumulation of protonsgenerates a pH/Proton gradient
and a transmembrane electrical
--- Content provided by FirstRanker.com ---
potential that creates a proton
motive force.
A Large Drop in Redox
--- Content provided by FirstRanker.com ---
Potential across each of the
three Respiratory Enzyme
--- Content provided by FirstRanker.com ---
Complexes (I,III,IV).Provides the Energy for H+
Pumping
--- Content provided by FirstRanker.com ---
Electron Transport (Oxidative
Process) is coupled to Phosphorylation
ATP is synthesized when 3
--- Content provided by FirstRanker.com ---
protons flow back from
intermembrane space of
--- Content provided by FirstRanker.com ---
mitochondria tomitochondrial matrix through
an enzyme complex ATP
--- Content provided by FirstRanker.com ---
synthase.
Oxidation of fuels and
--- Content provided by FirstRanker.com ---
phosphorylation of ADPare coupled by a proton
gradient across an inner
--- Content provided by FirstRanker.com ---
mitochondrial membrane.
Thus Oxidative phosphorylation
is process in which ATP is
--- Content provided by FirstRanker.com ---
formed
As a result of transfer of
--- Content provided by FirstRanker.com ---
electrons from NADH orFADH2 to O2 by a series of
electron carriers.
--- Content provided by FirstRanker.com ---
Mechanism
Of
--- Content provided by FirstRanker.com ---
Oxidative PhosphorylationOxidative Phosphorylation
Oxidation tightly coupled
--- Content provided by FirstRanker.com ---
with PhosphorylationE.T.C (Oxidation)Process
coupled with phosphorylation
--- Content provided by FirstRanker.com ---
of ADP+pi to generate ATP.
Hypothesis And Theories Mechanism
--- Content provided by FirstRanker.com ---
OfOxidative Phosphorylation
Chemical Coupling Hypothesis
--- Content provided by FirstRanker.com ---
Conformational Coupling Hypothesis
Chemiosmotic Theory
Chemical Coupling Hypothesis:
--- Content provided by FirstRanker.com ---
Put forward by Edward Slater (1953)
Proposed series of high energy
--- Content provided by FirstRanker.com ---
phosphorylated intermediates areproduced during E.T.C operation.
Which are used to produce ATP.
--- Content provided by FirstRanker.com ---
Conformational Coupling
Hypothesis
--- Content provided by FirstRanker.com ---
Paul Boyer 1964Mitochondrial Cristae undergo
conformational change in the
--- Content provided by FirstRanker.com ---
components of E.T.C.E.T.C components attain high
energy state which are responsible
--- Content provided by FirstRanker.com ---
for the ATP production.
Chemiosmotic Theory
--- Content provided by FirstRanker.com ---
Put forward by Peter Mitchell (1961)
(Nobel Prize, 1978)
--- Content provided by FirstRanker.com ---
E.T.C process and ATP synthesis iscoupled by a proton gradient
developed in intermembrane space of
--- Content provided by FirstRanker.com ---
mitochondria.
Mitchell's Postulates for
--- Content provided by FirstRanker.com ---
Chemiosmotic TheoryIntact inner mitochondrial
membrane is required
--- Content provided by FirstRanker.com ---
Electrons are pumped through ETC
complexes I,III and IV.
--- Content provided by FirstRanker.com ---
Generates a Proton gradient andin intermembrane space of
mitochondria.
--- Content provided by FirstRanker.com ---
Proton pumps are Complexes I,
--- Content provided by FirstRanker.com ---
III and IV.Protons return through ATP synthase
Oxidative Phosphorylation
--- Content provided by FirstRanker.com ---
Proton gradient in intermembrane space creates Proton
Motive Force due to:
--- Content provided by FirstRanker.com ---
Proton gradient have a
thermodynamic tendency
--- Content provided by FirstRanker.com ---
Proton gradient createsElectrochemical potential
difference
--- Content provided by FirstRanker.com ---
Proton Motive Force drives the
Protons from mitochondrial
--- Content provided by FirstRanker.com ---
intermembrane space back tomatrix side
Through a specific site of F0 and
--- Content provided by FirstRanker.com ---
F1 particle of ATP Synthase.
ATP Synthase catalyzes the
phosphorylation of ADP with pi
--- Content provided by FirstRanker.com ---
In a reaction driven by movement
of H+ across the inner membrane
--- Content provided by FirstRanker.com ---
back into the matrix through it.Translocation of protons through
ATP Synthase
--- Content provided by FirstRanker.com ---
Stimulates and activates ATP
Synthase
--- Content provided by FirstRanker.com ---
For catalytic action ofphosphorylation- ADP with pi to
form ATP.
--- Content provided by FirstRanker.com ---
Supports mechanism of Oxidative
Phosphorylation.
--- Content provided by FirstRanker.com ---
Flow of three H+ through an ATP
Synthase complex
--- Content provided by FirstRanker.com ---
Brings a conformational change ndomains of ATP Synthase
Which causes the ATP synthase
--- Content provided by FirstRanker.com ---
activate and catalyze
phosphorylation reaction
--- Content provided by FirstRanker.com ---
To synthesize ATP from ADP + Pi.ATP Synthase, a Molecular Mill.
--- Content provided by FirstRanker.com ---
ATP synthesis at F1 results from
repetitive conformational changes
as rotates
--- Content provided by FirstRanker.com ---
rotates 1/3 turn-
energy for ATP release
This process of producing ATP
--- Content provided by FirstRanker.com ---
is known as oxidative
phosphorylation.
--- Content provided by FirstRanker.com ---
Entire process of using Proton
gradient and proton motive
--- Content provided by FirstRanker.com ---
force to make ATP is calledChemiosmosis.
During oxidative
--- Content provided by FirstRanker.com ---
phosphorylation total energychange is released in small
increments.
--- Content provided by FirstRanker.com ---
So that energy can be trapped as
chemical bond energy and form
--- Content provided by FirstRanker.com ---
ATP.Coupling of ATP synthesis to
respiration is indirect, via a H+
--- Content provided by FirstRanker.com ---
electrochemical gradient.
Overview of Oxidative Phosphorylation
--- Content provided by FirstRanker.com ---
+
+
--- Content provided by FirstRanker.com ---
++ +
+
--- Content provided by FirstRanker.com ---
-
-
--- Content provided by FirstRanker.com ---
--
As electrons flow through complexes of ETC, protons are translocated
--- Content provided by FirstRanker.com ---
from matrix into the intermembrane space.
The free energy stored in the proton concentration gradient is tapped
as protons reenter the matrix via ATP synthase.
--- Content provided by FirstRanker.com ---
As result ATP is formed from ADP and Pi.ATP Translocation From
--- Content provided by FirstRanker.com ---
Mitochondria
Through ATP/ADP Translocases
--- Content provided by FirstRanker.com ---
ATP molecules produced in Oxidative
Phosphorylation mechanism are
--- Content provided by FirstRanker.com ---
Transported out of mitochondrialmatrix through specific transporters
Operation Of ETC
--- Content provided by FirstRanker.com ---
Glycolysis, Fatty
--- Content provided by FirstRanker.com ---
acid oxidationTCA cycle
supplies NADH
--- Content provided by FirstRanker.com ---
and FADH2 to
the Electron
--- Content provided by FirstRanker.com ---
Fatty AcidsAcetyl Co A
Transport Chain
--- Content provided by FirstRanker.com ---
Pyruvate
Amino Acids
--- Content provided by FirstRanker.com ---
GlucoseWHY ETC OPERATES ?
During E.T.C operation total
--- Content provided by FirstRanker.com ---
energy change is released insmall increments
So that energy can be trapped
--- Content provided by FirstRanker.com ---
as chemical bond energy to
form ATP.
When two redox couples of ETC
--- Content provided by FirstRanker.com ---
differ from each other by 0.22 volts
in standard redox potential.
--- Content provided by FirstRanker.com ---
At this site free energy in the form ofheat released which is more than 7.3
Kcal.
--- Content provided by FirstRanker.com ---
This free heat energy is conserved to
undergo Phosphorylation reaction
--- Content provided by FirstRanker.com ---
and generate chemical form ofenergy-ATP.
Sites in E.T.C at which
--- Content provided by FirstRanker.com ---
energy liberated is less
than 7.3 Kcal is simply
--- Content provided by FirstRanker.com ---
dissipiated in theform of heat.
Three sites in E.T.C (Complex
--- Content provided by FirstRanker.com ---
I,III and IV) where heat energyliberated more than 7.3 Kcal
Utilized for phosphorylation
--- Content provided by FirstRanker.com ---
reaction of ADP with pi to
form ATP.
--- Content provided by FirstRanker.com ---
Electrons are transferred fromNADH+H+ O via multisubunit
2
--- Content provided by FirstRanker.com ---
inner membrane complexes I, III
& IV, plus CoQ & Cytochrome c.
--- Content provided by FirstRanker.com ---
Within each complex, electronspass sequentially through a series
of electron carriers.
--- Content provided by FirstRanker.com ---
Complex I catalyzesoxidation of NADH+H+ with
reduction of coenzyme Q:
--- Content provided by FirstRanker.com ---
NADH + H+ + FP NAD+ + FPH2
Coenzyme Q accepts 2 e- and picks
up 2 H+ from FPH2 to yield the fully
--- Content provided by FirstRanker.com ---
reduced QH2.
Succinate Dehydrogenase of the Krebs Cycle is
also called complex II or Succinate-CoQ
--- Content provided by FirstRanker.com ---
Reductase.
FAD is initial e- acceptor.
--- Content provided by FirstRanker.com ---
FAD is reduced to FADH2 during oxidation ofSuccinate to Fumarate.
FADH2 generated by Succinate
--- Content provided by FirstRanker.com ---
Dehydrogenase reaction gets reoxidized
by transfer of electrons through a series
--- Content provided by FirstRanker.com ---
of 3 iron-sulfur centers to CoQ, yieldingCoQH2.
QH2 product may be reoxidized via
--- Content provided by FirstRanker.com ---
complex III.
Providing a pathway for transfer of
--- Content provided by FirstRanker.com ---
electrons from Succinate into respiratorychain.
Complex III/ Cytochrome b-c1
--- Content provided by FirstRanker.com ---
complex accepts electrons fromcoenzyme QH2 that is generated
by electron transfer in complexes
--- Content provided by FirstRanker.com ---
I & II.
Cytochrome c resides in
--- Content provided by FirstRanker.com ---
intermembrane space.It alternately binds to
complex III or IV during e-
--- Content provided by FirstRanker.com ---
transfer.
Significance Of ETC
Reduced coenzymes gets reoxidized
--- Content provided by FirstRanker.com ---
to NAD+ /FAD in ETC for its
reutilization in metabolic oxidation
--- Content provided by FirstRanker.com ---
reactions.Reduced coenzymes NADH+
H+/FADH2 give its reducing
--- Content provided by FirstRanker.com ---
equivalents to E.T.C components and
get reoxidized.
--- Content provided by FirstRanker.com ---
E.T.C generates chemical form ofenergy ATP as a valuable by product.
P/O Ratio
--- Content provided by FirstRanker.com ---
Ratio of ATPs formed perOxygen reduced
OR
--- Content provided by FirstRanker.com ---
Number of ATPs generated
per Oxygen atom used in
--- Content provided by FirstRanker.com ---
ETC process.To make 1 ATP need 30 kJ/mole
There needs more than one
--- Content provided by FirstRanker.com ---
proton to translocate duringETC process to generate 1 ATP.
Ten protons are pumped out of
--- Content provided by FirstRanker.com ---
the matrix during the two electrons
flowing from NADH+H+ to O2
--- Content provided by FirstRanker.com ---
(Complex I, III and IV).Six protons are pumped out of the
matrix during the two electrons
--- Content provided by FirstRanker.com ---
flowing from FADH2 to O2
(Complex III and IV).
Spontaneous electron flow
--- Content provided by FirstRanker.com ---
through each of complexes I, III, &
IV is coupled to H+ ejection from
--- Content provided by FirstRanker.com ---
matrix to intermembrane SpaceA total of 10 H+ are ejected from the mitochondrial matrix per 2 e
- transferred from NADH to oxygen via the respiratory chain.
--- Content provided by FirstRanker.com ---
A total of 6 H+ are ejected from the mitochondrial matrix per 2 e-
transferred from FADH2 to oxygen via the respiratory chain.
Complex I and Complex III transports 4H+
--- Content provided by FirstRanker.com ---
out of the mitochondrial matrix per 2e-
transferred from NADH.
--- Content provided by FirstRanker.com ---
Thus there are 2H+ per 2e- that areeffectively transported by complex
IV.
--- Content provided by FirstRanker.com ---
ATP Yield
3
--- Content provided by FirstRanker.com ---
4
4
--- Content provided by FirstRanker.com ---
210 protons translocates
per NADH+H+
--- Content provided by FirstRanker.com ---
6 protons translocates
per FADH2
Proton gradient and Proton
--- Content provided by FirstRanker.com ---
motive Force created as
electrons transferred to
--- Content provided by FirstRanker.com ---
Oxygen forming water10 H+ / NADH+H+
6 H+ / FADH2
--- Content provided by FirstRanker.com ---
F F couples ATP synthesis to H+1 o
transport into the mitochondrial matrix.
--- Content provided by FirstRanker.com ---
Transport of least 3 H+ per ATP isrequired.
Translocation of 3H+
--- Content provided by FirstRanker.com ---
required by ATP Synthase foreach ATP produced
1 H+ needed for transport of Pi.
--- Content provided by FirstRanker.com ---
Net: 4 H+ transported for
each ATP synthesized
--- Content provided by FirstRanker.com ---
through ATP Synthase.P:O Ratio for NADH+H+
10 H+ X 1 ATP = 2.5 ATP
--- Content provided by FirstRanker.com ---
4 H+
P.O Ratio for FADH2
--- Content provided by FirstRanker.com ---
6 H+ X 1 ATP = 1.5 ATP4 H+
P:O ratio for NADH: 10 H+/4H+ =
--- Content provided by FirstRanker.com ---
2.5 ATPP:O ratio for FADH2: 6 H+/ 4H+ =
1.5 ATP
--- Content provided by FirstRanker.com ---
ATP Is A Valuable Byproduct Of
Oxidative Phosphorylation
ATP is a high energy phosphate
--- Content provided by FirstRanker.com ---
compound
Biologically important free
--- Content provided by FirstRanker.com ---
nucleotideATP has Two High Energy Phosphate
Anhydride Bonds
--- Content provided by FirstRanker.com ---
ATP is energy currency of
cell.
--- Content provided by FirstRanker.com ---
Predominantly generatedthrough Oxidative
Phosphorylation.
--- Content provided by FirstRanker.com ---
Sites Of ATP Production In ETC3 sites Of ATP Generation in ETC
Site I/Complex I-
--- Content provided by FirstRanker.com ---
Electrons transferred from Complex I to
CoQ
--- Content provided by FirstRanker.com ---
Site II/Complex III-Electrons transferred from Cyt b to Cyt c1.
Site III/Complex IV-
--- Content provided by FirstRanker.com ---
Electrons transferred from Cytochrome
aa3/Complex IV/Cytochrome Oxidase to ?
--- Content provided by FirstRanker.com ---
O2Thus ATP Generation
Is Due To Transformation Of
--- Content provided by FirstRanker.com ---
Heat Energy Into Chemical Form Of Bond EnergyWhich Satisfy Law Of Thermodynamics
Energy Is never Destructed
--- Content provided by FirstRanker.com ---
Energy Is Transformed From One Form To Another
From One System To Another
--- Content provided by FirstRanker.com ---
One Body To AnotherSignificance OF ATP
ATP allows coupling of
--- Content provided by FirstRanker.com ---
thermodynamically
unfavorable reactions
--- Content provided by FirstRanker.com ---
to favorable reactions.Uses of ATP generated in
Oxidative Phosphorylation
--- Content provided by FirstRanker.com ---
?Synthetic/Anabolic reactions?Active transport mechanism.
?Muscular contraction
?Nerve impulse conduction.
--- Content provided by FirstRanker.com ---
ATP is continually beinghydrolyzed and
regenerated
--- Content provided by FirstRanker.com ---
A person at rest
consumes and regenerate
--- Content provided by FirstRanker.com ---
3 ATP/ secStaying Alive Energy Wise
We need 2000 Cal/day or 8,360 kJ of energy per day
Each ATP gives 30.5 kJ/mole of energy on hydrolysis
--- Content provided by FirstRanker.com ---
We need 246 moles of ATPBody has less than 0.1 moles of ATP at any one time
We need to make 245.9 moles of ATP
Each mole of Glucose yields 38 ATPs or 1160 kJ
We need 7.2 moles of Glucose (1.3 kg or 2.86 pounds)
--- Content provided by FirstRanker.com ---
Each mole of Stearic acid yields 147 ATPs or 4,484 kJWe need 1.86 moles of stearic acid (0.48 kg or 1.0
pound of fat)
--- Content provided by FirstRanker.com ---
RememberCoQ accepts electrons and
Protons by complexes I and II
--- Content provided by FirstRanker.com ---
Acceptance of Protons and
Electrons from Complex II by
--- Content provided by FirstRanker.com ---
CoQ does not generate ATPE.T.C is a Mode For Free Radical
Generation
--- Content provided by FirstRanker.com ---
During E.T.C operation thereoccurs leakage of small amounts
of electrons
--- Content provided by FirstRanker.com ---
Which are transferred directly
to oxygen to form super oxide
--- Content provided by FirstRanker.com ---
ion (Free radicals/ROS)What is a Free Radical ?
--- Content provided by FirstRanker.com ---
Any chemical species with one of moreunpaired electrons
Unstable/Highly Reactive to get
--- Content provided by FirstRanker.com ---
stabilized
Powerful Oxidant
Short half life (nanoseconds)
--- Content provided by FirstRanker.com ---
Can exist freely in environmentMain Factors Responsible for
ETC
--- Content provided by FirstRanker.com ---
Factors For Universal MetabolismNutrition
Environment
Life Style Habits
--- Content provided by FirstRanker.com ---
Factors Associated To ETC
Metabolites- Carbs ,Proteins , Lipids
--- Content provided by FirstRanker.com ---
Vitamins , Minerals and AntioxidantsOxygen Concentration
Respiration Process
--- Content provided by FirstRanker.com ---
Hemoglobin Structure and Function
Mitochondrial DNA
--- Content provided by FirstRanker.com ---
Metabolic StatusOxidative Stress
REGULATORS OF OXIDATIVE
--- Content provided by FirstRanker.com ---
PHOSPHORYLATIONImportant Direct Substrates
Regulators Of Oxidative Phosphorylation
--- Content provided by FirstRanker.com ---
and ATP Generation
NADH/FADH2
--- Content provided by FirstRanker.com ---
O2ADP and pi
Indirect Substances Involved
--- Content provided by FirstRanker.com ---
GlucoseFatty acids
Insulin
Amino acids and Proteins
Iron
--- Content provided by FirstRanker.com ---
Vitamin CVitamin B Complex members- Niacin,
Riboflavin
--- Content provided by FirstRanker.com ---
ATP/ADP RatioRegulates Mechanism Of
Oxidative Phosphorylation
--- Content provided by FirstRanker.com ---
Respiratory Control
The most important factor in determining the rate of
--- Content provided by FirstRanker.com ---
oxidative phosphorylation is the level of ADP.
The regulation of the rate of oxidative phosphorylation by
the ADP level is cal ed respiratory control
--- Content provided by FirstRanker.com ---
ADP and pi is required for ETC
process.
--- Content provided by FirstRanker.com ---
Intramitochondrial ratioATP/ADP is a control
mechanism
--- Content provided by FirstRanker.com ---
At high ATP/ADP ratioATP acts as an allosteric
inhibitor for Complex IV
--- Content provided by FirstRanker.com ---
(Cytochrome Oxidase)Inhibition is reversed by
increasing ADP levels.
--- Content provided by FirstRanker.com ---
ADP levels reflect rate of ATP
consumption and energy state
--- Content provided by FirstRanker.com ---
of the cell.At low ADP levels ? Low
oxidative phosphorylation
--- Content provided by FirstRanker.com ---
Electron transport is tightly coupled tophosphorylation.
ATP cannot be synthesized by
--- Content provided by FirstRanker.com ---
oxidative phosphorylation unless there
is heat energy released from electron
--- Content provided by FirstRanker.com ---
transport.Electrons do not flow through the
electron-transport chain to O2 unless
--- Content provided by FirstRanker.com ---
ADP is phosphorylated to ATP.
Inhibitors OF
--- Content provided by FirstRanker.com ---
ETC ComplexesOR
Inhibitors Of
--- Content provided by FirstRanker.com ---
Oxidative Phosphorylation
ETC Complexes Inhibitors
OR
--- Content provided by FirstRanker.com ---
Interruptors of Oxidative Phosphorylation
Mechanism
--- Content provided by FirstRanker.com ---
Enemies/Distractors of ETC componentswho stop its normal operation.
Block ETC operation and stop ATP
--- Content provided by FirstRanker.com ---
generation.
ETC Complexes Inhibitors
--- Content provided by FirstRanker.com ---
Chemical compounds having affinity for ETCcomponents/complexes
Chemically interact with ETC complexes, bind and
--- Content provided by FirstRanker.com ---
inactivate them
Affects normal functional operation of ETC
--- Content provided by FirstRanker.com ---
Low/No ATP productionCessation of cellular activities
Complex I/Site I - E.T.C Inhibitors
--- Content provided by FirstRanker.com ---
vAmobarbital /AmytalvRotenone (Fish/Rat Poison)
vMercurials
vPiercidin ?A
--- Content provided by FirstRanker.com ---
(Volatile Anesthetics)
vHalothane (Malignant Hyperthermia)
vFluothane
vIsoflurane
--- Content provided by FirstRanker.com ---
vSevofluraneComplex III/ Site II -E.T.C Inhibitors
vBritish Anti Lewisite ( BAL)
--- Content provided by FirstRanker.com ---
vAntimycin ?AvDimercaprol
Complex IV/Site III /Cytochrome
--- Content provided by FirstRanker.com ---
Oxidase Inhibitors :
--- Content provided by FirstRanker.com ---
vCyanidevCarbon Monoxide
vH2S
vAzide
Complex V Inhibitors
--- Content provided by FirstRanker.com ---
ATP Synthase Inhibitors
Oligomycin
--- Content provided by FirstRanker.com ---
Fo particle of ATP Synthase serve asproton channel
An antibiotic Oligomycin binds with
--- Content provided by FirstRanker.com ---
Fo particle of ATP Synthase
Do not translocate Protons through
--- Content provided by FirstRanker.com ---
it.Inhibits activation of ATP Synthase
phosphorylation of ADP to ATP.
--- Content provided by FirstRanker.com ---
AtractylosideA Glycoside prevents
translocation of ADP across
--- Content provided by FirstRanker.com ---
mitochondrial membrane.
Make it unavailable for
--- Content provided by FirstRanker.com ---
phosphorylation reactionBongregate
Pseudomonas toxin has
--- Content provided by FirstRanker.com ---
inhibitory action similar
like Atractyloside.
Artificial Electron Acceptors/
--- Content provided by FirstRanker.com ---
Distractors Of ETC
These chemicals
--- Content provided by FirstRanker.com ---
arrest respirationby inhibition of
ETC complexes
--- Content provided by FirstRanker.com ---
Specific inhibitors of
Electron Transport Chain
--- Content provided by FirstRanker.com ---
and
ATP-Synthase
--- Content provided by FirstRanker.com ---
Uncouplers Of
Oxidative
--- Content provided by FirstRanker.com ---
Phosphorylation
What are Uncouplers?
--- Content provided by FirstRanker.com ---
Uncouplers are chemical agents
Uncouplers are mostly lipid soluble
--- Content provided by FirstRanker.com ---
aromatic weak acidsThey Uncouple/Delink two tightly
coupled natural processes
--- Content provided by FirstRanker.com ---
E.T.C (Oxidation) uncoupled from
Phosphorylation (ATP generation)
--- Content provided by FirstRanker.com ---
They just carry out Oxidationwithout Phosphorylation
--- Content provided by FirstRanker.com ---
Uncouplers break theconnection between
Electron Transport Chain and
--- Content provided by FirstRanker.com ---
Phosphorylation
Electron transport is a motor
--- Content provided by FirstRanker.com ---
Phosphorylation is the transmissionUncouplers put the car in NEUTRAL
Uncouplers Action Il ustrates
--- Content provided by FirstRanker.com ---
As Total Solar Eclipse
Uncouplers just bring oxidation
(E.T.C/Sun Rise) without
--- Content provided by FirstRanker.com ---
phosphorylation(Interrupted Sun Light)
Uncoupler (Moon In between) inhibits
--- Content provided by FirstRanker.com ---
generation of ATP ( Dark/No Day)Types Of Uncouplers
Physiological Uncouplers
--- Content provided by FirstRanker.com ---
Thermogenin /Uncoupling Protein-1Excess of Thyroxine
Long Chain Fatty acids
Unconjugated Hyperbilirubinemia
--- Content provided by FirstRanker.com ---
Chemical Uncouplers2,4 Di Nitro Phenol
Di Nitro Cresol
Dicumarol
--- Content provided by FirstRanker.com ---
Aspirinp-Triflouromethoxy Carbonyl Cyanide
Phenylhydrazone (FCCP)
--- Content provided by FirstRanker.com ---
ValinomycinPentachlorophenol
Snake Venom-Phospholipases
--- Content provided by FirstRanker.com ---
Mode Of Action Of UncouplersCertain Uncouplers are ionophores,
lipophilic substances.
--- Content provided by FirstRanker.com ---
They carry protons from
intermembrane space across
--- Content provided by FirstRanker.com ---
mitochondrial membrane to matrixFrom site other than specific site.
(i.e not through F0 and F1 particles of
--- Content provided by FirstRanker.com ---
ATP Synthase).
Certain Uncouplers changes
permeability of mitochondrial
--- Content provided by FirstRanker.com ---
membrane to protons.
Translocate protons easily
--- Content provided by FirstRanker.com ---
through mitochondrialmembrane.
--- Content provided by FirstRanker.com ---
2,4 DNP dissolve in membrane and function ascarriers for H+.
--- Content provided by FirstRanker.com ---
Uncouplers block oxidative phosphorylation by
dissipating H+ electrochemical gradient.
Protons pumped out leak back into mitochondrial
--- Content provided by FirstRanker.com ---
matrix,
preventing development of proton gradient and
proton motive force.
--- Content provided by FirstRanker.com ---
ATP Synthase reaction runs backward
in presence of an uncoupler.
w Hydrolysis of ATP is spontaneous.
--- Content provided by FirstRanker.com ---
Thus Uncouplers by their actiondeplete proton gradient of
intermembrane space during
--- Content provided by FirstRanker.com ---
ETC operation.
Uncouplers Dissipate More Heat
--- Content provided by FirstRanker.com ---
Uncouplers Do not allow to developrequired proton gradient and
Do not form proton motive force in the
--- Content provided by FirstRanker.com ---
intermembrane space of mitochondria
No translocation of Protons through ATP
--- Content provided by FirstRanker.com ---
SynthaseCauses no stimulation or activation of ATP
Synthase
--- Content provided by FirstRanker.com ---
No catalysis of Phosphorylation of ADP with
pi to generate ATP.
During uncoupling phenomena
--- Content provided by FirstRanker.com ---
Free energy released as Heat energy
--- Content provided by FirstRanker.com ---
more than 7.3 Kcal is not conserved forPhosphorylation reaction dissipiated as
it is in form of heat
--- Content provided by FirstRanker.com ---
A very high heat energy released then
causes swelling of Mitochondria and
--- Content provided by FirstRanker.com ---
exhibit malignant hyperthermia.Physiological Uncoupling
By
--- Content provided by FirstRanker.com ---
Uncoupling Protein (UCP-1)
--- Content provided by FirstRanker.com ---
An Uncoupling Protein (UCP-1)/Thermogenin is produced in brown
adipose tissue of newborn mammals and
--- Content provided by FirstRanker.com ---
hibernating mammals.
This UCP-1 protein of an inner
--- Content provided by FirstRanker.com ---
mitochondrial membrane functions as aH+carrier.
--- Content provided by FirstRanker.com ---
Uncoupling by UCP-1 protein blocks
development of a H+ electrochemical
--- Content provided by FirstRanker.com ---
gradient, thereby stimulatingrespiration.
Free energy of ETC is dissipated as heat.
--- Content provided by FirstRanker.com ---
Uncoupling of ETC and
phosphorylation occurs in animals
--- Content provided by FirstRanker.com ---
as a means to produce heatNon shivering thermogenesis
Occurs in brown adipose tissues
--- Content provided by FirstRanker.com ---
(rich in mitochondria)Significance Of Physiological
--- Content provided by FirstRanker.com ---
UncouplersIn extreme cold conditions and in
hibernating animals
--- Content provided by FirstRanker.com ---
Physiological Uncouplers bring
uncoupling phenomena
--- Content provided by FirstRanker.com ---
The heat liberated inside body helpsto restore and maintain body
temperature.
--- Content provided by FirstRanker.com ---
Brown adipose
(fat) cells
contain natural
Uncouplers to
--- Content provided by FirstRanker.com ---
warm animalscold adaptation
and hibernation.
--- Content provided by FirstRanker.com ---
As per the Required condition OfBody
This "non-shivering
--- Content provided by FirstRanker.com ---
thermogenesis" is costly in
terms of respiratory energy
--- Content provided by FirstRanker.com ---
Heat energy unavailable forATP synthesis
But provides valuable warming
--- Content provided by FirstRanker.com ---
to an organism.
Effect Of Poor Antioxidant Activity
--- Content provided by FirstRanker.com ---
ETC Inhibitors and Uncouplers
Any compound that stops
--- Content provided by FirstRanker.com ---
electron transport will stoprespiration...this means you
stop breathing
--- Content provided by FirstRanker.com ---
Electron transport can be
stopped by inhibiting ATP
--- Content provided by FirstRanker.com ---
synthesisAn uncoupler breaks the
connection between ATP
--- Content provided by FirstRanker.com ---
synthesis and electron
transport
Shuttle Systems
--- Content provided by FirstRanker.com ---
Shuttling Reducing Equivalents
OF NADH+H+
--- Content provided by FirstRanker.com ---
from Cytosol into theMitochondrion
--- Content provided by FirstRanker.com ---
ShuttleA vehicle or aircraft that travels regularly
between two places
--- Content provided by FirstRanker.com ---
Biochemical shuttle is a biochemical
system for translocating Protons and
--- Content provided by FirstRanker.com ---
electrons produced during GlycolysisAcross a semipermeable inner membrane
of mitochondrion
--- Content provided by FirstRanker.com ---
For oxidative phosphorylation mechanism
NADH+H+ is generated in the cytosol during
--- Content provided by FirstRanker.com ---
GlycolysisCytosolic NADH+H+ itself is not
carried across the mitochondrial
--- Content provided by FirstRanker.com ---
membrane.Instead its Protons and
Electrons of NADH+H+ are
--- Content provided by FirstRanker.com ---
carried through shuttle
systems.
--- Content provided by FirstRanker.com ---
Since NAD+ and NADH +H+ areimpermeable to an inner
mitochondrial membrane
--- Content provided by FirstRanker.com ---
This reducing equivalents must be
shuttled into mitochondrial matrix
--- Content provided by FirstRanker.com ---
before they can enter the ETC.Cytosolic NADH+H+
Enter Mitochondria
--- Content provided by FirstRanker.com ---
via2 Shuttle Systems
Two shuttles Involved:
--- Content provided by FirstRanker.com ---
Malate-Aspartate Shuttle
Glycerol 3-phosphate Shuttle
--- Content provided by FirstRanker.com ---
Malate-Aspartate Shuttle
Malate/Aspartate Shuttle System
Malate Aspartate Shuttle
--- Content provided by FirstRanker.com ---
Active in Heart and Liver.
2.5 molecules of ATP are produced
Glycerol-3-Phosphate Shuttle
--- Content provided by FirstRanker.com ---
Glycerol-3-Phosphate Shuttle
Glycerol 3 Phosphate Shuttle
--- Content provided by FirstRanker.com ---
Glycerol Phosphate ShuttleActive in Skeletal muscles and
Brain
--- Content provided by FirstRanker.com ---
FADH2 formed in this enter the
electron-transport chain through
--- Content provided by FirstRanker.com ---
CoQGenerates only 1.5 molecules of
ATP
--- Content provided by FirstRanker.com ---
Summary of Shuttle Systems
Total ATPs Generated / 1 Glucose Oxidation
--- Content provided by FirstRanker.com ---
Heart and Liver32.0 ATP
Uses Malate Aspartate Shuttle
--- Content provided by FirstRanker.com ---
Muscle and Brain
30.0 ATP
--- Content provided by FirstRanker.com ---
Uses Glycerol phosphate ShuttleFactors Affecting
Oxidative Phosphorylation
--- Content provided by FirstRanker.com ---
MechanismOxygen supply to cells
Hemoglobin structure and function
Respiratory system and its function
--- Content provided by FirstRanker.com ---
Mitochondrial structure and ETCcomponents.
Presence of Nutrients
Enzyme function and
--- Content provided by FirstRanker.com ---
Coenzymes availability
Adequate amount of ADP
--- Content provided by FirstRanker.com ---
and pi.Presence of ETC inhibitors
Pathological Conditions Affecting
--- Content provided by FirstRanker.com ---
Oxidation Phosphorylation
Mechanism
--- Content provided by FirstRanker.com ---
WhichLower Down ATP Production
1. Hypoxia
--- Content provided by FirstRanker.com ---
2. Anemia3. Ischemia
--- Content provided by FirstRanker.com ---
4. Hemoglobinopathies
5. Emphysema
--- Content provided by FirstRanker.com ---
6. Respiratory Distress Syndrome7. Asthma
8. Prolonged Starvation
--- Content provided by FirstRanker.com ---
9. Malnutrition
10. Diabetes mellitus
--- Content provided by FirstRanker.com ---
11. ETC inhibition by chemicals/drugs12. Inherited Disorders of Mitochondria
Inherited /Genetic Disorders
--- Content provided by FirstRanker.com ---
Related To Mitochondrial
Oxidative Phosphorylation
--- Content provided by FirstRanker.com ---
MechanismMitochondrial DNA
Mitochondrial genes encode for ETC complexes
--- Content provided by FirstRanker.com ---
Complex IComplex III
Complex IV
Complex V
--- Content provided by FirstRanker.com ---
Mutations in any one or more genes ofmitochondrial DNA controlling mechanism of Oxidative
phosphorylation lead to its inherited disorders
--- Content provided by FirstRanker.com ---
1. MELAS
An inherited disorder caused due to defect
--- Content provided by FirstRanker.com ---
of complex I or IV of E.T.CAssociated with
Mitochondrial Myopathy
--- Content provided by FirstRanker.com ---
EncephalopathyLactate accumulation
Acidosis
Stroke
2. Fatal Infantile Mitochondrial Myopathy
--- Content provided by FirstRanker.com ---
Defect in E.T.C components
located in mitochondria
--- Content provided by FirstRanker.com ---
Cytochrome c Oxidase defectAssociated with renal
dysfunction.
--- Content provided by FirstRanker.com ---
Mostly fatal in early age3. Leber's Hereditary
Optic Neuropathy (LHON)
--- Content provided by FirstRanker.com ---
Caused due to mutations in
mitochondrial DNA
--- Content provided by FirstRanker.com ---
Affects oxidativephosphorylation mechanism
Loss of bilateral vision due to
--- Content provided by FirstRanker.com ---
neuroretinal degeneration.
Mutant Genes Of LHON
--- Content provided by FirstRanker.com ---
4. Mitochondrial DNA Deletion
--- Content provided by FirstRanker.com ---
Syndrome--- Content provided by FirstRanker.com ---
5. Luft's Disease
--- Content provided by FirstRanker.com ---
Luft's Disease is a mitochondrial diseaseFirst patient who was diagnosed with this
disease was a 30 year old Swedish woman by
--- Content provided by FirstRanker.com ---
Dr Rolf Luft
Caused by abnormal mitochondria
Biochemical Cause
--- Content provided by FirstRanker.com ---
Mitochondria Respire Wildly
Respiratory control is lost
Partial Uncoupling is caused by an abnormality in
--- Content provided by FirstRanker.com ---
mitochondrial membrane
Electron transport is only loosely coupled to ATP
--- Content provided by FirstRanker.com ---
productionOxidation process proceed independent of ADP
phosphorylation to generate ATP
--- Content provided by FirstRanker.com ---
An extra energy evolves in form of heat
This elevates body temperature up to 38.4 ?C which
raises BMR
--- Content provided by FirstRanker.com ---
Luft's Disease Is Characterized By
Abnormal excessive production of heat
--- Content provided by FirstRanker.com ---
Characterized by hypermetabolism andabnormal transpiration.
Patient experiences excessive sweating
--- Content provided by FirstRanker.com ---
during winter
Make them to change their clothes 10 times a
--- Content provided by FirstRanker.com ---
day.Onset is in childhood
Thyroid function is normal
--- Content provided by FirstRanker.com ---
Since there is less ATP productionand an extra energy is lost in the
form of heat
--- Content provided by FirstRanker.com ---
Metabolic processes are stimulated
Luft's Disease
--- Content provided by FirstRanker.com ---
Non Thyroidal HypermetabolismDue to high BMR and low ATP production
High caloric intake
There is failure to put on weight despite a good diet
--- Content provided by FirstRanker.com ---
There is progressive weight loss despite increased foodintake
Excessive perspiration
--- Content provided by FirstRanker.com ---
Excessive thirst indicate a state of severe hypermetabolism of non thyroid origin (since thyroid hormones
-T3 and T4 are normal)
--- Content provided by FirstRanker.com ---
Manifestations of Luft's Disease
Heat intolerance
--- Content provided by FirstRanker.com ---
Profuse perspirationPolydipsia without polyuria
Severe hyper metabolism
Polyphagia
Muscular wasting and weaken
--- Content provided by FirstRanker.com ---
Absent deep reflexes, and Restingtachycardia.
Multiorgan Dysfunction Risk In
--- Content provided by FirstRanker.com ---
Luft's Disease
Case Study
An elderly couple was brought by ambulance to an emergency
--- Content provided by FirstRanker.com ---
department after their daughter noticed that they were both
acting "strangely." The couple had been in good health prior
--- Content provided by FirstRanker.com ---
to the weekend. Their daughter had gone out to spend theweek-end with her friends. The couple had been snowed in at
their house until the snowplows cleared the roads. They had
--- Content provided by FirstRanker.com ---
plenty of food and were kept warm by a furnace and blankets.
On reaching home after two days, their daughter noticed that
--- Content provided by FirstRanker.com ---
they both were complaining of bad headaches, confusion,fatigue, and some nausea. On arrival to an emergency
department, both patients were afebrile with normal vital
--- Content provided by FirstRanker.com ---
signs and O2 saturation of 99 percent on 2 L of O2 by nasal
cannula. Their lips appeared to be very red. Both patients were
--- Content provided by FirstRanker.com ---
slightly confused but otherwise oriented. The physicalexaminations were within normal limits.
Carboxyhemoglobin levels were drawn and were elevated.
--- Content provided by FirstRanker.com ---
What is most likely cause of these patients' symptoms?
Questions
--- Content provided by FirstRanker.com ---
Long Essays.
Q.1 Define Biological oxidation.
--- Content provided by FirstRanker.com ---
Enumerate and Describe variousenzymes carrying out biological
oxidation reactions with suitable
--- Content provided by FirstRanker.com ---
examples.
Q.2 Describe Respiratory chain and
Give its significance.
--- Content provided by FirstRanker.com ---
OR
Explain the Electron. Transport chain
(E.T.C.) and its significance.
--- Content provided by FirstRanker.com ---
OR
How the reduced equivalents generated
in anaerobic dehydrogenase reactions
--- Content provided by FirstRanker.com ---
are reoxidized.
Q.3 What is oxidative
--- Content provided by FirstRanker.com ---
phosphorylation? Explainthe mechanism with
respect to various theories
--- Content provided by FirstRanker.com ---
and hypothesis.
Short Notes
Cytochromes
--- Content provided by FirstRanker.com ---
Inhibitors of E.T.CShuttle systems and its
significance
--- Content provided by FirstRanker.com ---
Inhibitors and Uncouplers ofoxidative phosphorylation
Complexes of E.T.C.
--- Content provided by FirstRanker.com ---
Redox potential and free energychanges.
Inherited Disorders related to E.T.C.
--- Content provided by FirstRanker.com ---
abnormality.
ATP ? Mode of its formation and
--- Content provided by FirstRanker.com ---
it's role in the Body.Short Answer Questions
Give the sites for ATP generation
--- Content provided by FirstRanker.com ---
of in E.T.C.Enumerate the High energy
compounds of our body
--- Content provided by FirstRanker.com ---
Substrate level phosphorylation
and it's importance.
--- Content provided by FirstRanker.com ---
Enumerate the Enzymescatalyzing Biological oxidation
reactions. Write the class to
--- Content provided by FirstRanker.com ---
which these enzymes classified.
Inherited Disorders of
--- Content provided by FirstRanker.com ---
Mitochondrial DysfunctionDefine P.O ratio. What is the P:O
ratio for reduced NADH+H+ &
--- Content provided by FirstRanker.com ---
FADH2 respectively.List the components of E.T.C. and
their location.
--- Content provided by FirstRanker.com ---
Redox couple & Redox potential.
FlavoProteins
Product of Aerobic and
--- Content provided by FirstRanker.com ---
Anaerobic dehydrogenation
reactions.
--- Content provided by FirstRanker.com ---
Write enzymes catalyzingAerobic and Anaerobic
dehydrogenation reaction's
--- Content provided by FirstRanker.com ---
during metabolism.
THANK YOU
Laboratory data showed lactic acidosis,
--- Content provided by FirstRanker.com ---
ProteinuriaGlycosuria and
Generalized aminoaciduria
Muscle biopsy showed large clumps of
--- Content provided by FirstRanker.com ---
granules positive with oxidative enzymestains and increased lipid droplets.
Ultrastructural studies showed large
--- Content provided by FirstRanker.com ---
aggregates of mitochondria, many of which
were greatly enlarged and contained
--- Content provided by FirstRanker.com ---
disoriented or concentric whorls of cristaeand paracrystalline inclusions.
A 1-month-old boy was admitted because of failure to thrive.
--- Content provided by FirstRanker.com ---
He was floppy and had bilateral ptosis, diminished reflexes, andpoor suck. He had aspiration pneumonia, developed seizures,
and died at age 3 1/2 months.
--- Content provided by FirstRanker.com ---
He was an only child, and family history was negative.
Cytochrome c oxidase was absent in fresh frozen sections
by histochemical staining.
--- Content provided by FirstRanker.com ---
By biochemical assay, cytochrome c oxidase (cytochrome aa3)
was 6% of normal in muscle biopsy and undetectable in autopsy
--- Content provided by FirstRanker.com ---
muscle; spectra and content of cytochromes showed lack ofcytochrome aa3, decreased cytochrome b and normal
cytochrome cc1.
--- Content provided by FirstRanker.com ---
In kidney, cytochrome-c-oxidase activity was 38% of normal
and spectra showed decreased cytochromes aa3 and b.
--- Content provided by FirstRanker.com ---
The association of fatal infantile mitochondrial myopathy,lactic acidosis and renal dysfunction was previously reported
by Van Biervliet et al and appears to be a distinct nosologic
--- Content provided by FirstRanker.com ---
entity, one of the few biochemically defined mitochondrial
myopathies.
--- Content provided by FirstRanker.com ---
A case of cytochrome c oxidase deficiency primarily affectingskeletal muscle is described. The child was admitted at 4
weeks due to failure to thrive and examination at that time
--- Content provided by FirstRanker.com ---
revealed weakness and hypotonia. His condition deteriorated
until at 11 weeks respiratory arrest necessitated artificial
--- Content provided by FirstRanker.com ---
ventilation and death occurred at 14 weeks. Biochemicalinvestigation showed lactic acidemia and generalized
aminoaciduria. Histochemical examination of muscle obtained
--- Content provided by FirstRanker.com ---
at biopsy showed strong reactions for some oxidative enzymes,
but by contrast cytochrome c oxidase could not be detected.
--- Content provided by FirstRanker.com ---
Cytochrome c oxidase activity was less than 5% of controlvalues in an extract of fresh muscle. The reduced-minus
oxidized absorption spectra of muscle mitochondrial fractions
--- Content provided by FirstRanker.com ---
prepared from post-mortem tissue showed an absence of
cytochrome aa3 and a partial deficiency of cytochrome b. Ultra
--- Content provided by FirstRanker.com ---
-structural examination showed abnormal mitochondria withloss of cristae and an abnormal granular matrix. The family
history suggests autosomal recessive inheritance.
--- Content provided by FirstRanker.com ---