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Date Submitted: 04/23/2016 03:39 PM
University of Pennsylvania
Chemistry 251-001: Principles of Biological Chemistry
Problem Set 3
Due: April 19, 2016
50 points
1. Describe the effect of the following substances on both cellular respiration (oxygen consumption by the electron transport chain) and oxidative phosphorylation (ATP synthesis by the Fo/F1 ATPase complex). (6 points total, 2 points each)
A. Antimycin - an antibiotic that inhibits respiratory complex III
Respiratory complex III is a complex that couples the transfer of electrons from ubiquinol (QH2) to cytochrome c, regenerating ubiquinone in the process (Q). The net reaction of the complex is shown below
QH2 + 2 cyt c1 (oxi.) + 2 H+ (N) -> Q + 2 cyt c1 (red.) + 4 H+ (P)
If this complex was inhibited by the antiobiotic Antimycin, it would greatly disrupt the Q-cycle since ubiquinol (QH2) would be unable to regenerate to (Q), and also prevent the the reduction of cytochrome c1. These effects would also disrupt the activities of the complexes I and II (both require Q as an electron/proton acceptor), and complex IV (requires reduced cytochrome c1). The net effect of this would be the disruption of the formation of the proton gradient across the mitochondrial membrane. Therefore, the production of ATP through the ATP synthase complex would be inhibited, as protons are unable to flow through the ATP synthase complex in the absence of a proton gradient (ATP will be on the surface of the enzyme but unable to leave).
Furthermore, this inhibition could likely have effects on other parts of cellular respiration (due to feedback). Since the activities of complexes I and II are disrupted by the lack of Q, NADH would not be oxidized to NAD+ (since the electrons from NADH are normally transferred to Q). Thus and excess of NADH would be built up with no way to convert it to NAD+, leading to disruption of glycolysis and the citric acid cycle (which both require NAD+ as an electron acceptor)
B....