dr.s.chakravarty, md. instructions : handwritten submissions only(i.e pen and paper) draw diagrams...
TRANSCRIPT
![Page 1: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/1.jpg)
Biological Oxidation
Dr.S.Chakravarty, MD
![Page 2: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/2.jpg)
Home assignment Due date :-21st Sep 2015
Instructions : Handwritten submissions only(i.e pen and paper)
Draw diagrams wherever required You can contact me if you face any difficulties.
1.Describe the factors that influence enzyme activity .Write a short note on Vmax and Km
(8+2 = 10 marks )
2. Describe competitive and non- competitive inhibition with examples. (10 marks )
![Page 3: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/3.jpg)
Oxidation is defined as the removal of electrons and reduction as the gain of electrons.
Oxidation is always accompanied by reduction of an electron acceptor.
![Page 4: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/4.jpg)
Oxidation : Reduction :
Oxidation and reduction:
• Loss of electrons
• Loss of hydrogen
• Gain of oxygen
• Gain of electrons
• Gain of hydrogen
• Loss of oxygen
![Page 5: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/5.jpg)
REDOX POTENTIAL
• When a substance exists both in the reduced state and the oxidized state , the pair is called a REDOX COUPLE.
• The redox potential of this couple is estimated by measuring the EMF of a sample half cell connected to a standard half-cell.
![Page 6: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/6.jpg)
1M H + ~ H gas @ 1 Atmospheric pressure
E0’ =0 meV
Salt bridge
![Page 7: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/7.jpg)
• WHEN A SUBSTANCE HAS LOWER AFFINITY FOR ELECTRONS THAN HYDROGEN IT HAS A NEGATIVE REDOX POTENTIAL
• ELECTRONS MOVE ALWAYS FROM MORE ELECTRONEGATIVE TO ELECTROPOSITIVE
LOSS OF FREE ENERGY
(THIS ALWAYS ENSURES THAT FREE ENERGY DECREASES)
![Page 8: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/8.jpg)
Redox Potentials
Oxidant Reductant E0’ ( in V)
NAD + NADH + H + -0.32
Cytochrome b+++ Cytochrome b ++ +0.07
Co-eneyme Q Co-eneyme QH2 +.010
Cytochrome c +++ Cytochrome c ++ +0.22
Cytochrome a +++ Cytochrome a +++ +0.29
½ O2 +2H H2O +0.82
![Page 9: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/9.jpg)
• ½ O2 + 2H+ H2O (E0’ = +0.82 )
• NAD+ + H + NADH (E0’ = -0.32)• E0’ = +0.82 – (-0.32 ) = 1.14
• COMBINE BOTH OF THESE :-
½ O2 + NADH + H+ H2O + NAD+
Δ G0 = -nFΔE0
= - 2 x 23.06 x 1.14 = -52.6 kcal/mol
![Page 10: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/10.jpg)
02 H2O
FOOD(REDUCED )
SMALLER MOLECULES
REDUCED COENZYMES
e.g NAD
ENERG
Y
BIOLOGIOCAL OXIDATION
e-
ELECTRON TRANSPORT CHAIN
MITOCHONDRION
![Page 11: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/11.jpg)
Harper’s Illustrated Biochemistry
![Page 12: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/12.jpg)
With the help of successive reductions in the electron transport chain assembly , this energy change is released in small increments so that the body can utilize it .
![Page 13: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/13.jpg)
HIGH ENERGY COMPOUNDS
• THESE COMPOUNDS WHEN HYDROLYSED RELEASE A LARGE AMOUNT OF ENERGY
• INDICATED BY SQUIGGLE (~)
• FREE ENERGY VARIES FROM -7 TO -15 kcal/mol
![Page 14: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/14.jpg)
![Page 15: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/15.jpg)
Substrate level Phosphorylation• Defn :- When the energy of high energy compound is directly transferred
to nucleoside diphosphate to form a triphosphate without the help from electron transport chain.
• Examples :-
1.Bisphosphoglycerate kinase ( Glycolysis)(1,3 bisphosphoglycerate 3-phosphoglycerate)
2. Pyruvate kinase (Glycolysis)(Phosphoenol pyruvate Pyruvate)
3. Succinate thiokinase (TCA cycle) (Succinyl CoA Succinate ) usmle
![Page 16: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/16.jpg)
Impermeable to ions and most other compounds
MITOCHONDRIA The mitochondrion contained the enzymes responsible for electron transport and oxidative phosphorylation
USMLE concept!
![Page 17: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/17.jpg)
The MITOCHONDRION – powerhouse of the cell
Harper’s Illustrated Biochemistry
![Page 18: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/18.jpg)
IMPORTANT MITOCHONDRIAL TRANSPORTERS
Pyruvate PyruvateHydrogen Hydrogen
Malate MalateCitrate Citrate
ADP ADPATP ATP
INNER MITOCHONDRIAL MEMBRANE
![Page 19: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/19.jpg)
The mitochondrial membrane is impermeable to NADH….. So, how does cytosolic NADH reach there ??
![Page 20: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/20.jpg)
Malate –Aspartate shuttle
Operates in Liver , Kidney and Heart
![Page 21: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/21.jpg)
Glycerol -3 –phosphate shuttle
Operates mainly in muscle and Brain.
![Page 22: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/22.jpg)
• The flow of electrons occurs through successive dehydrogenase enzymes in mitochondria , together known as the electron transport chain (ETC).
(the electrons are transferred from lower to higher redox potential)
Electron transport chain
![Page 23: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/23.jpg)
Electron Carriers- The transfer of electrons is not directly to oxygen but through coenzymes
NAD+
FMN
FeS
ubiquinoneFAD FeS
Cyt b
FeS Cyt c1 Cyt c Cyt a Cyt a3
1/2 O2
ubiquinone
![Page 24: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/24.jpg)
Protein complexes:
• NADH-CoQ Dehydrogenase (Complex I)
• Succinate-CoQ Dehydrogenase (Complex II)
• CoQ-cytochrome c Reductase (Complex III)
• Cytochrome c Oxidase (Complex IV)
• Mobile complexes:1. Co-enzyme Q or ubiquinone2. Cyt C
![Page 25: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/25.jpg)
COMPLEX IFMN-FeS
Complex IIIFeS-Cytb-Cyt c1Co Q
Complex IV
Cyt a-a3(Fe+3,Cu+2)
Cyt C
COMPLEX IIFeS
8.Succinate9. Fatty Acyl CoA 10. Glycerol 3-PFAD
Mitochondrial Matrix
NAD
1.Glyceraldehyde -3P2.Isocitrate3.Malate4.Glutamate5.β-OH-acyl CoA
2H +
½ O2
H2O
+
SITE 1 4 PROTONS PUMPED OUT
SITE 24 PROTONS PUMPED OUT
SITE 32 PROTONS PUMPED OUT
Fp(FAD) lipoate 6.Pyruvate 7.α-ketoglurarate
Inner mitochondrial membrane
USMLE !
![Page 26: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/26.jpg)
1
2
3 4
Harper’s Illustrated Biochemistry
![Page 27: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/27.jpg)
COMPLEX I-NADH CoQ REDUCTASE
• Also known: NADH dehydrogenase complex.
• Tightly bound to the inner membrane.
• Contains a flavoprotein (Fp)- FMN (Favin mono nucleoide): prosthetic group and an iron-sulphur protein (Fe-S).
![Page 28: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/28.jpg)
Complex 1 NADH FMN Reduced FeS Q
NAD FMNH2 Oxidized FeS QH2
• Large negative free energy change; energy released is 12 kcal/mol. This is utilized to drive 4 protons out of the mitochondria.
• 1 ATP is produced.
![Page 29: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/29.jpg)
COMPLEX II:SUCCINATE-CoQ-REDUCTASE
• The electrons from FADH2 enter ETC at the level of CoQ.
• This step does not liberate enough energy to produce ATP.
• The 3 major enzyme systems that transfer their electrons directly to ubiquinone are:
USMLE !! a. Succinate dehydrogenase( TCA cycle )b. Fatty acyl CoA dehydrogenase( Fatty acid oxidation)c. Mitochondrial glycerol phosphate dehydrogenase.
Succinate FAD Reduced FeS Q
Fumarate FADH2 Oxidized FeS QH2
USMLE !
![Page 30: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/30.jpg)
Iron-sulfur centers (Fe-S) are prosthetic groups containing 1-4 iron atoms
Iron-sulfur centers transfer only one electron, even if they contain two or more iron atoms.
E.g., An Fe center might cycle between redox states:Fe+++ (oxidized) + 1 e- Fe++
(reduced)
Iron-sulfur Centers (clusters)
![Page 31: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/31.jpg)
![Page 32: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/32.jpg)
COENZYME Q• The ubiquinone is reduced
successively to semiquinone (QH) and finally to quinol (QH2)
It accepts a pair of electrons from NADH or FADH2 through complex I or complex II respectively.
Co-enzyme Q is a quinone derivative having long isoprenoid tail.
2 molecules of cytochrome c are reduced.
The Q cycle thus facilitates the switching from the 2 electron carrier ubiquinol to the single electron carrier cytochrome c.
This is a mobile carrier.
![Page 33: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/33.jpg)
COMPLEX III: CYTOCHROME REDUCTASE• Cluster of iron-sulphur proteins, cytochrome b and cytochrome c1• Prosthetic group in both- heme• Iron in heme shuttles between Fe3+ and Fe2+ forms.• Free energy change: -10kcal/mol• 4 protons pumped out.
QH2 FeS Cyt b Cyt c1 Cyt C(Red) (Fe+3) (Fe+2) (Fe+3) (Fe+2)
Q FeS Cyt b Cyt c1 Cyt C(oxi) (Fe+2) (Fe+3) (Fe+2) (Fe+3)
![Page 34: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/34.jpg)
Cytochrome C
• Contains one heme prosthetic group .
• It collects electrons from Complex III and delivers to Complex IV.
• It is also the mediator of apoptosis (programmed cell death)
![Page 35: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/35.jpg)
COMPLEX IV: CYTOCHROME OXIDASE• Contains cytochrome a and
cytochrome a3
• Tightly bound to inner mitochondrial membrane.
• 2 protons are pumped out.
• Cytochrome oxidase- 2 heme groups and 2 copper ions.
• Functional unit of enzyme: cytochrome a-a3.
![Page 36: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/36.jpg)
Cyt C Cyt a-a3 2H2O
(Fe +2) (Fe+3, Cu +2)
Cyt C Cyt a-a3 O2
(Fe +3) (Fe+2, Cu +3)FINAL ELECTRON
ACCEPTOR
![Page 37: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/37.jpg)
CHEMIOSMOTIC THEORY(Peter Mitchell. N.P 1978)
• The transport of electrons from inside to outside of inner mitochondrial membrane is accompanied by the generation of a proton gradient across the membrane.
• Protons accumulate outside the membrane creating an electrochemical potential.
• This drives the synthesis of ATP by ATP synthase .
![Page 38: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/38.jpg)
Harper’s Illustrated Biochemistry
![Page 39: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/39.jpg)
Harper’s Illustrated Biochemistry
![Page 40: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/40.jpg)
• The pH outside is 1.4 units lower than inside . • The outside is positive 0.14V relative to inside.• The proton motive force (PMF ) IS 0.224 v
corresponding to a free energy change of 5.2 kcal/mol of protons.
![Page 41: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/41.jpg)
• ENERGETICS OF ATP SYNTHESIS
– ENERGY RELEASED = 52kcal/mol– Synthesis of 1ATP and Pi requires 7.3 ATP
molecules– Chemical energy trapped = 7.3 x 3 = 21.9kcal =
40%– Rest 60% energy is dissipated as HEAT !!
![Page 42: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/42.jpg)
F0 – F1 complex :Fo complex: –INHIBITED BY OLIGOMYCIN Made of 12 subunits . H+ passes through each subunit
from membrane space to inner space rotating the Fo complex (turbines).
![Page 43: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/43.jpg)
F1 complex: Has 9 polypeptide chains ,(3 alpha , 3 beta , 1 gamma , 1 sigma , 1 epsilon)
the α chains have binding sites for ATP and ADP and beta chains have catalytic activity.
ATP SYNTHESIS NEEDS Mg +2 IONS• ADP and Pi bind the alpha subunit• Binding change mechanism - conformation change of beta
subunits causes release of ATPs from the complex.
• ATPs formed in the mitochondrial matrix are translocated to cytosol by ATP/ADP translocase
![Page 44: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/44.jpg)
1 ) ADENINE NUCLEOTIDE TRANSPORTER2)H+/Pi SYMPORT
Harper’s Illustrated Biochemistry
![Page 45: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/45.jpg)
EARLIER ESTIMATES WERE WRONG!!
• According to recent estimates , NADH may generate only 2.5 ATPs while FADH2 may generate only 1.5 ATP.
• So , instead of 38 ATP , only 32 ATPs are generated from glucose .
![Page 46: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/46.jpg)
ATP IS THE ENERGY CURRENCY
![Page 47: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/47.jpg)
INHIBITORS OF ATP SYNTHESIS
• 1. SITE SPECIFIC INHIBITORS:-
– Site : COMPLEX 1 to Co Q• Alkylguanide(guanethide), hypotensive drug • Rotenone ( insecticide and rat poison)• Chlorpromazine (tranquilizer)• Barbiturates (sedative) • Pericidin (antibiotic)
USMLE !
![Page 48: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/48.jpg)
• Site :COMPLEX III• BAL –BRITISH ANTI LEWISITE – WAR GAS• Napthoquinone
• Site : Complex IV inhibitors– Carbon monoxide – Cyanide– Azide – Hydrogen Sulphide
• Site : between succinate dehydrogenase and CoQ– Carboxin– Malonate : competetive inhibitor of Succinate DH
USMLE !
![Page 49: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/49.jpg)
USMLE ! Lewisite is an organoarsenic compound. It was once manufactured in the U.S., Japan, and Germany for use as a chemical weapon, acting as a vesicant (blister agent) and lung irritant.Later causes liver necrosis and death.
(Dimercaprol)
(Thenoyltrifluoroacetone)
(Insecticide)
![Page 50: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/50.jpg)
• Site specific inhibitors of Oxidative Phosphorylation– Actractlyoside inhibits translocase whereas
oligomycin acts through one of the proteins present in Fo-Fi stalk.
– Ionophores are lipid soluble compunds that increase the permeability of lipid bilayers to certain ions.• TYPES
– MOBILE ION CARRIERS eg.Valinomycin( allows K+ to permeate mitochondria and dissipate proton gradient)
– CHANNEL FORMERS eg.Gramicidin
![Page 51: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/51.jpg)
![Page 52: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/52.jpg)
UNCOUPLERS
• ALLOW OXIDATION TO PROCEED BUT THE ENERGY IS DISSIPATED AS HEAT .– EG. • 2,4 dinitro phenol, • 2,4 dinitro cresol • pentachlorophenol• CCCP (Chloro carbonyl cyanide phenyl hydrazone)• THERMOGENIN in brown adipose tissue• Thyroxine
TOXICITY : PRESENTS WITH INCREASED BODY TEMPERATURE
![Page 53: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/53.jpg)
Mitochondrial inherited diseases :
• Heteroplasmy – proportion of somatic cells which are affected to normal cells.
• Threshold – the amount of affected DNA should reach threshold before it can manifest.
• Affects mainly Neurons and muscle – which require high ATPs for metabolism.
![Page 54: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/54.jpg)
MELAS ( complex 1 or complex 1 and 4 defect)
• Mitochondrial encephalopathy• Lactic acidosis• Stroke like episodes.
• Cause : mutation in the mitochondrial DNA• Abnormality in the t-RNA ( A G mutation)• Deficiency of complex proteins impaired oxidative
phosphorylation.• OXPHOS – transient oxidative phosphorylation in brain
stroke like symptoms.
![Page 55: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/55.jpg)
Leber’s Hereditary Optic Neuropathy – LHON complex -3 defect
• Degeneration of Retinal ganglion layer.
• Specially maculo-papular bundle.
• Central loss of vision in mid 20’s.
• Increased reactive oxygen species apoptosis of cells.
![Page 56: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/56.jpg)
Kearns-Sayre syndrome
• Oculocraniosomatic neuromuscular disease with ragged red fibers
• Triad of :1. Chronic progressive external ophthalmoplegia
2. Bilateral pigmentary retinopathy – salt and pepper appearance of retina
3. Cardiac conduction abnormalities
• Other defects include short stature and ataxia.
![Page 57: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/57.jpg)
Leigh’s disease
• Subacute Necrotizing Encephalomyelopathy (SNEM)
• lactic acidemia, Developmental delay, seizure, extraocular palsies, and hypotonia
• Fatal by age of 2 years.
• Complex -4 defect
![Page 58: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/58.jpg)
• A comatose laboratory technician is rushed into the emergency room. She dies while you are examining her. Her most dramatic symptom is that her body is literally hot to your touch, indicating an extremely high fever. You learn that her lab has been working on metabolic inhibitors and that there is a high likelihood that she accidentally ingested one. Which one of the following is the most likely culprit?
• Barbiturates• Piericidin A• Dimercaprol • Dinitrophenol • Cyanide
![Page 59: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/59.jpg)
• A 53-year-old, previously successful man recently lost his job and is under investigation for racketeering. His wife returns home to find him slumped over the steering wheel of his idling car in the closed garage. He is unresponsive and has a cherry color to his lips and cheeks. Which of the following is inhibited ?
A. Complex I of the ETCB. Cytochrome oxidaseC. The ATP-ADP antiporterD. The F0 component of the F0-F1 ATPase
E. The F1 component of the F0-F1 ATPase
![Page 60: Dr.S.Chakravarty, MD. Instructions : Handwritten submissions only(i.e pen and paper) Draw diagrams wherever required You can contact me if you face any](https://reader035.vdocument.in/reader035/viewer/2022062722/56649f395503460f94c5647c/html5/thumbnails/60.jpg)
Thank you