INHIBITORS ETC INHIBITORS are compounds that prevent/ interrupts the transfer of electrons by binding to a various complex of the chain which blocks the redox reactions. This results in the blockage of proton pumping, ATP synthesis and oxygen uptake. NOTE : All complexes do not function independently. So any blockage at any point in the chain prevents the formation of ATP. If the movement is blocked anywhere the carrier on the oxidized site of the block has no source of electron and carrier on the reduced site has no electron to donate. There are inhibitors of ETC for every complexes except Complex II: INHIBITORS OF COMPLEX-1 include: RETONONE (fish poison) Rotenone is a plant product. Rotenone is extracted from roots of plant Derris elliptica. It is a botanical pesticide. It is a strong inhibitor of complex I of the electron transport chain. In the presence of this insecticide, it inhibits the NADH electrons to transport through the NADH-CoQ reductase complex,resulting in the an inability to produce ATP from the oxidation of NADH. Certain tribes use it as a fish poison which paralyse the fish.. Rotenone is a member of the class of rotenones that consists of 1,2,12,12atetrahydrochromeno[3,4-b]furo[2,3-h]chromen-6(6aH)-one substituted at position 2 by a prop-1-en-2-yl group and at positions 8 and 9 by methoxy groups. a methoxy group is the functional group consisting of a methyl group bound to oxygen. (R−O−CH₃.) AMYTAL (Amorbarbital) It a type of bartiburate sedative hypnotic drugs that is used to treat sleep disorders or as Preanesthetic agents for surgeries in a medical or hospital setting. Amytal is a Schedule II drug under the Controlled Substances Act, meaning it has medically designated purposes but runs a high risk of abuse and dependence. Amobarbital is a member of the class of barbiturates that is pyrimidine-2,4,6(1H,3H,5H)trione substituted by a 3-methylbutyl and an ethyl group at position 5. PERICIDINE (purga) It is a type of antibiotic of microbial origin. Its mode of action is similar to Rotenone. Antibiotics are medications that destroy or slow down the growth of bacteria. INHIBITORS OF COMPLEX-3 include: ANTIMYCIN A one of the first known and most potent inhibitors of the mitochondrial respiratory chain. It is an antibiotic from Streptomyces species (soil bacteria) INHIBITORS that prevent the flow electrons from ubiquinonol (QH²) to cytochrome bc1 complex (complex III). In this case, components preceding complex III become fully reduced, and those after it become oxidized. INHIBITORS OF COMPLEX-4 include : CYANIDE(CN-) a poisonous chemical compound found certain bacteria, fungi and algae. Cyanides are also found in cigarette smoke, in vehicle exhaust and even in foods. can be natural or man made ( hydrogen cyanide found in gas) binds to Fe3+ in heme-containing proteins in cytochrome c. This prevents the cytochrome C to send electrons to oxygen and blocklock of complex IV by cyanide depletes ATP culminating in cell death. CARBON MONOXIDE (CO) an odorless, colorless gas. It is produced any time a fossil fuel is burned and it can cause sudden illness and death. CO inactivates cytochrome oxidase. This leads to decreased ATP production, especially in tissues with high metabolic demands (brain, heart). The electron transport chain continues, generating superoxide radicals — (donate single electrons (e-) or steal efrom other molecules.) leading to further damage. AZIDE IONS ( N3-) it is well known that sodium azide. inhibits oxidative phosphorylation via inhibition of cytochrome oxidase, the final enzyme in the mitochondrial electron transport chain, thereby resulting in a rapid depletion of intracellular ATP. INHIBITORS OF ATP SYNTHASE COMPLEX (PHOSPHORYLATION INHIBITOR) prevent the synthesis of ATP by binding to the ATP synthase complex. It prevents the inflow of protons. OLIGOMYCIN polypeptide in nature act as an antibiotic which is obtained from the Streptomyces species. It stops the transfer of high energy phosphate group to adenine diphosphate (ADP). binds to a 23kd polypeptide in the F0 base plate and blocks ATP synthesis by the F0 /F1 ATPase. It prevents respiration in mitochondria and all ATP-driven functions in submitochondrial. DICLYCLOHEXYL CARBO DIIMIDE (DCCD) It makes covalent bonds with amino acid glutamate of the c subunit of F0. When it binds covalently, it stops the proton channel, which prevents the formation ATP synthesis.