Various compounds are added to mitochondria having a tightly coupled oxidative phosphorylation system. Addition of which of the following substrates will generate the LEAST amount of ATP?
Rotenone is a site-specific inhibitor of electron trans­port. it acts at the level of complex I. Malate feeds electrons to reduced nicotinamide adenine dinucleo­tide (NADH), which in turn is passed into the electron transport system at the level of complex I, through NADH dehydrogenase just before the blockage in­duced by this drug. Therefore, no electrons can be transported from NADH and no adenosine triphos­phates (ATPs) are made. Succinate feeds in electrons from the reduced form of flavin adenine dinucleotide (FADH2) at the level of complex II, through the action of succinyl dehydrogenase. Complex II passes its elec­trons to coenzyme Q at a point beyond the site of rotenone inhibition; therefore, rotenone has no inhibi­tory effect and 2 ATPs are produced per atom of oxygen consumed. (The number of ATPs produced per atom of oxygen used is often expressed as the number of phosphate ions taken up divided by the atoms of oxygen used. This is called the P/O ratio.) in the absence of any inhibitor, the P/O ratio for malate is 3 and for succinate 2.
Actinomycin D is an inhibitor of DNA synthesis, not oxidative phosphorylation. The inhibitor of elec­tron transport is actinomycin A.
Malate
Succinate
Malate with rotenone
Succinate with rotenone