Transcript
Dr. V. Siva Prabodh MD.
Professor
High energy phosphates & Low energy phosphates:
CompoundPhosphoenolpyruvate -14.8
Carbamoyl phosphate -12.3
1,3 – Bisphosphoglycerate -11.8
Creatine phosphate -10.3
ATP ADP + Pi -7.3
ADP AMP + Pi -6.6
Pyrophosphate -6.6
Glucose 1-phosphate -5.0
Fructose 6 –phosphate -3.8
AMP -3.4
Glucose 6 –phosphate -3.3
Glycerol 3-phosphate -2.2
Kcal/mol
-7.3ATP ADP +Pi
Adenosine Triphosphate (ATP)
Importance of Adenosine Triphosphate (ATP) ATP serves as the general "free energy
currency" for virtually all cellular processes.
It is a direct source of energy for cell motility, muscle contraction, and the specific transport of substances across membranes.
ATP is a source of phosphate energy for synthesis of the other nucleoside triphosphates via the reaction:
ATP is also an allosteric effector of many enzymes.
cytochromes: Protein-bound :- Heme containing carriers
Cytochromes constitute a family of colored proteins containing the Heme prosthetic group
Nature of e- Carriers: Protein-bound carriers :- Iron-sulphur centers
Fe ion is coordinated with the sulphurs of cysteine residues and inorgnic sulphur atoms.
Nature of e- Carriers: Mobile carriers :- Coenzyme Q
Coenzyme Q: small hydrophobic molecule and the only one that is not a part of protein.
Organization of carriers in ETC: Complex I
NADH dehydrogenase complex :
Largest Respiratory enzyme complex> 40 polypeptide chainsBound FMNAt least 7 iron-sulfur centersElectron transfer From NADH to Co QBlocked by Rotenone and Amytal
Complex IISuccinate Dehydrogenase :
It is a point of entry of electrons from FADH2 produced by the enzyme succinate dehydrogenase in the citric acid cycle.
FAD as Prosthetic group Iron-sulfur proteins Electron transfer From FADH2 to Co Q Thus, both complexes I and II donate their
electrons to the same acceptor, coenzyme Q.
Coenzyme Q : Benzoquinone linked to 10 isoprene units
It has the ability to accept electrons in pairs and pass them one at a time through a semiquinone intermediate to Complex III. This cycle is referred to as the Q cycle.
Electron transfer From Complex I or II to Complex III
Cytochrome c : This small mobile protein accepts
e- from Complex III and shuttles them to Complex IV
Complex III
Cytochrome b-c1 complex :
It is a Dimer Each monomer has: 3 Hemes bound to cytochromes 1 Iron-sulfur protein Electron transfer From Co Q to cytochrome c Cytochrome c then transfers e- to the
complex IV Blocked by Antimycin A
Complex IV
Cytochrome oxidase complex :
Dimer
Each monomer has: 13 Different polypeptide chains, including 2 Cytochromes a and a3 and 2 Cu atoms
Accepts one Electron at a time from Cytochrome c and passes them four at a time to Oxygen
Blocked by Cyanide, Azide, and Carbon monoxide
Organization of carriers in ETC:
Oxidative Phosphorylation Chemical coupling
Chemiosmotic hypothesis
- proposed by Mitchel
- dependent on proton gradient.
Chemiosmotic Coupling:
1. The active transport of electrons pumps protons out of the mitochondrial matrix into the inter membrane space.
2. An electrochemical gradient of protons is created, outside the inner mitochondrial membrane than inside.
The protons on the outside have a thermodynamic tendency to flow back in.
3. When protons do flow back into the matrix, the free energy arising from the gradient (21 kJ/mol of protons) is dissipated, with some of it being used to drive the ATP synthesis.
Chemiosmotic Coupling
ATP Synthase:
ATP synthase or F0F1 complex or
Complex V
Head F1
Stalk F0
P:O Ratio
The P:O ratio refers to: the number of Inorganic Phosphate
molecules utilized for ATP generation for every atom of Oxygen (a pair of e-) consumed.
.
P:O Ratio
Electrons entering the system at complex I from
NADH have a P/O ratio of about 3/1.
Electrons entering the system at complex II FADH2's have a P/O ratio of about 2/1.
ATP Synthesis by ATP Synthase
Boyer’s Binding Change Mechanism
Inhibitors of ETC
Inhibitors of ETC: Bind to one of the components of ETC and Block
the transport of Electrons.
At Complex I: Rotenone, Amytal & Piericidin A Between cyt b and c1: Antimycin A & BAL At Complex IV: CO, Cyanide, Azide & H2S
Inhibitors of Oxidative Phosphorylation:
Uncouplers: 2,4- DNP, FCCP (trifluoro carbonyl cyanide phenyl hydrazone)
Thyroxin, FFABlocks between oxidation and
phosphorylation
Ionophores: Valinomycin, Nigercin alters the permeability of mitochondrial
membrane
Other Inhibitors
Oligomycin: ATP synthase Atracyloside: Adenine nucleotide
carrier(Translocase)
Thank you
top related