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3. Occurs in mitochondrial inner membrane: ETC – Stepwise movement of electrons from high energy to
low energy that activates proton pump which transports proton from the mitochondrial matrix to
mitochondrial inter-membrane and generate Proton gradient.
6. Oxygen is the final electron acceptor: We breathe in oxygen with our lungs, transport it with red
blood cells in our arteries to cells, and oxygen is ultimately used inside the mitochondria of every cell to
accept electrons at the end of the electron transport chain to form water.
Each NADH yields 2.5 ATP and each FADH2 yields 1.5 ATP.
1. Glycolysis:
2 ATP
2. G1P is converted into glucose-6-phosphate (G6P) – this skips the 1st step of glycolysis catalized
by Glucokinase/Hexokinase which uses 1 ATP
NADH dehdrogenase
Ubiquinone (CoQ)
Cytochrome b/c1
Cytochrome c
ATP
Complex I: NADH : CoQ oxidoreductase
Ubiquinone (CoQ): Ubiquinone (QH2) is reduced to ubiquinol (free to diffuse within membranes)
Succinate dehydrogenase (In TCA cycle): converts succinate to fumarate and produces FADH2
from FAD
Other electron donors from FADH2 are: Fatty Acyl CoA Dehydrogenase, Glycerol 3 Phosphate
shuttle
Removes 4 electrons from 4 molecules of Cytochrome c and trasfers to O2 [In hypoxia, rate of
ETC and ATP production decreases, which leads to increase in glycolysis (anaerobic in the
abscence of oxygen) leading to lactic acidosis]
4 “C”s of Complex 4
Cytochrome oxidase
Copper/heme protein
Cyanide inhibits it
F0 component: Proton flows back to mitochondrial matrix from intermembrane space producing
energy
ATP:
3. Decreased ATP
Amobarbital/Amytal (Barbiturate)
Piercidin A
Thenoyltrifluoroacetone (TTA)
Malonate
Antimycin A (Antifungal)
Napthoquinone
Dimercaprol (ABC)
Phenformin
Myxothiazole
Azide
Hydrogen sulphide
Cyanide poisoning: Thiosulfate forms thiocyanate which is less toxic and excreted by kidneys; Nitrites
convert hemoglobin to methemoglobin (which binds cyanide in blood before reaching to tissues) – must
be given shortly after exposure
Carbon monoxide poisoning: Headache, nausea, tachycardia, tachypnea, cherry-red lips and cheeks,
respiratory depression and coma (treated with oxygen)
Complex V inhibitor:
Oligomycin (antibiotic)
Uncouplers uncouples ETC and oxidative phosphorylation by decreasing the proton gradient causing:
Because the rate of ETC increases, with no ATP synthsis, energy is released as heat. Important
uncouplers are:
Brown fat
Aspirin
Dinitrophenol
Mutations in mitochondrial DNA affect highly aerobic tissues (nerve, muscle) and is characterized by:
1. Maternal inheritance
2. LHON (Leber’s Hereditary Optic Neuropathy – Loss of Central vision): Mutation in Cytochrome
reductase
4. Leigh disease (lactic acidemia, developmental delay, seizure, extraocular palsies, hypotonia; fatal by
age 2): Mutation in Complex IV