You are testing a new small molecule inhibitor A that reduces ATP production, but you observed that it failed to inhibit any glycolysis-specific enzymes. You suspect it targets something in the TCA cycle or the electron transport chain. 1. Over-expression of wild type NADH dehydrogenase rescues wild type levels of ATP production under EXCESS inhibitor A treatment. 2. Inhibitor A does not reduce cytochrome c binding affinity to complex III or IV. 3. Co-treatment with both A and non-oxidizing NADH-mimic was lethal to cells. 4. Succinate-dehydrogenase is observed mostly bound to reduced FADH2 IN CELLS TREATED with A. WHICH IS THE MOST LIKELY BINDING SITE OF THIS MOLECULE? A. succinate-CoQ reductase: ubiquinone binding site B. cytochrome c oxidase: cytochrome c binding site C. NADH dehydrogenase: FMN binding site D. succinate-CoQ reductase: succinate binding site E. NADH dehydrogenase: ubiquinone binding site
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Step 1: The small molecule inhibitor A reduces ATP production but does not inhibit glycolysis-specific enzymes, suggesting it targets something in the TCA cycle or the electron transport chain. Show more…
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One measure of ATP-producing efficiency via oxidative phosphorylation is the P/O ratio, which equals the number of ATP produced per 1/2 O2 consumed (i.e., per electron pair donated into the respiratory chain and passed to the terminal acceptor). To determine the P/O ratio, you must first calculate the number of H+p consumed (i.e., allowed to favorably move down the proton electrochemical gradient) per ATP, which in a mitochondrion will equal: (# of c subunits in F-type ATP synthase + 3)/3. Then, you must divide the number of H+p generated per 1/2 O2 consumed (e.g., 10 for matrix NADH) by that value. Calculate the P/O ratio for mitochondrial oxidative phosphorylation, given a c11 F-type ATP synthase powered by matrix NADH. Enter your answer (a number only, rounded to the nearest tenth) in the space provided below.
Sri K.
Md.Daniyal A.
At what point in glycolysis can ATP act as an inhibitor? What kind of enzyme regulation occurs in this inhibition?
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