Biological oxidation bo 03
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Transcript of Biological oxidation bo 03
Dr. Aga Syed SameerCSIR Lecturer
Department of Biochemistry,
Medical College,
Sher-I-Kashmir Institute of Medical Sciences,
Bemina, Srinagar, Kashmir, 190018. India.
Biological
Oxidation
CHEMI-OSMOTIC THEORY
ATP SynthesisInhibitors of ETCUncouplers of ETCShuttle Systems
Electron Transference
NADH→FMN →FeS →CoQ
Succinate →FAD →FeS →CoQ
CoQ →FeS →Cytb →Cytc1 →Cytc
Cytc →Cytaa3 →O2
Oxidative Phosphorylation
The process of Phosporylation of ADP to ATP; coupled with the flow of via mitochondrial ETC
Dependency on ETC is because of Proton Pumps, which generate the H+ gradient across IMM by utilizing the energy of e-s flow
In addition, It also serves as proton pump; transporting H+s from inner chamber to Inner Membrane Space of Mitochondria
So, OP is cumulative function of ETC and ATP Synthase enzyme
ATP Synthase
F1-Fo ParticlesConsists of Head Piece – F1 and Base piece – Fo
attached with stalk
Fo component spans the IMM and forms an H+
channel or pore
F1 component catalyzes the phosphorylationof ADP to ATP by allowing the flow of H+
ions from Inter Membrane Space to Matrix via proton channel of Fo component
Thus, energy of proton gradient is utilized for the creation of ATP from ADP and Inorganic P
ATP Synthase
Chemiosmotic Theory
Proposed by Peter Mitchell in 1961
Flow of e-s through mitochondrial ETC and ATP synthesis are coupled by proton gradient that develops across the Inner Mitochondrial Membrane
Energy released during the transport of e-s from RE’s to O2 result in the efflux of H+ ions from Mitochondrial Matrix across IMM to Inner Membrane Space; Resulting in the generation of electro chemical proton gradient across IMM – 1.4pH unit
This electro chemical proton gradient serves as the potential source of energy for ATP synthesis
P:O RatioNumber of moles of inorganic phosphate (Pi)
utilized for ATP generating per gram atom of oxygen (half mole of O2) consumed
For NADH:
Complex I, II, IV are used for oxidation
10H+ are accumulated across IMM
Phosphorylation of 3 moles of ADP to ATP P:O Ratio = 3
For FADH2:
Complex III, IV are used for oxidation
6H+ are accumulated across IMM
Phosphorylation of 2 moles of ADP to ATP P:O Ratio = 2
Inhibitors
Complex I: Rotenones; Barbiturates (Amytal); Piericidin A; Chloropromazine; Alkylguanidines
Complex II: Malonate; Carboxin
Complex III: AntimycinA; BAL; Napthoquinone
Complex IV: Cyanide; H2S; CO; Sodium Azide
Other InhibitorsOligomycin: Antibiotic, which binds to Fo
subunit of ATP Synthase and blocks re-entry of protons into matrix thus preventing ATP synthesis
DiCyclohexylCarboDiimide (DCCD) : bonds covalently to a glutamic acid residue of the c subunit of Fo, proton flow through Fo is blocked and ATP synthase activity is inhibited
Atractyloside: Glycoside of plant Thistle, prventsOXPHOS by inhibiting Adenine Nucleotide Transporter/translocase (ANT) in IMM. Hence, blocks the supply of ADP for ATP synthase
UncouplersThey disrupt the tight
coupling between electron transport and the ATP synthase
2,4-dinitrophenolDicumarol, and Carbonyl Cyanide-p-
Trifluoromethoxyphenylhydrazone(fluorocarbonyl-cyanide phenylhydrazone or FCCP): 100x effective than DNP
UncouplersAdipose tissue in polar hibernating animals
contains so many mitochondria that it is called brown adipose tissue for the color imparted by the mitochondria.
The inner membrane of brown adipose tissue mitochondria contains an endogenous protein called thermogenin (literally, “heat maker”), or uncoupling protein, that creates a passive proton channel through which protons flow from the cytosol to the matrix.
IonophoresThey are lipophilic molecules that are capable of
binding and carrying ions across the biological membranes (by increasing the permeability of the membrane) and hence dissipating the proton gradient across IMM to inhibit OXPHOS
Valinomycin: Transports K ions
Nigercin: Transports K ions
Gramacidin: binds carries Na & K ions, and
Shuttle-Systems Most of the NADH used in electron transport is
produced in the mitochondrial matrix space, an appropriate site because NADH is oxidized by Complex I on the matrix side of the inner membrane
NADH produced in cytosol, if not oxidized to regenerate NAD, the glycolytic pathway would cease to function due to NAD limitation
Eukaryotic cells have a number of shuttle systems that harvest the electrons of cytosolic NADH for delivery to mitochondria without actually transporting NADH across the inner membrane
Malate-Aspartate
Liver
Heart
Kidneys
Malate-Aspartate
Glycero-PhosphateSkeletal Muscles
Brain
Questions?