Tutorial 3 - Metabolic Poisons Flashcards
Why is the rate of respiration in the presence of succinate and ADP greater than with glutamate + malate + ADP?
Malate feeds e- to ETC via the NADH dehydrogenase complex, which generates 3ATP per O atom reduced.
Succinate oxidation feeds e- to ETC chain via FADH2 and succinate dehydrogenase, which only produces 2 ATP per O atom reduced.
So to generate the same amount of ATP, more succinate must be oxidised than malate and glutamate so more oxygen is used, so respiration rate is higher.
What does cyanide do?
Binds covalently with Fe3+ in cytochrome oxidase, which inhibits the terminal step in ETC so respiration ceases.
What usually happens if oligomycin is added?
It is an ATP synthase inhibitor (less able to use H+ gradient), so would be expected to inhibit respiration (IN COUPLED MITOCHONDRIA).
What happens if oligomycin is added to uncoupled mitochondria?
(e.g. DNOC, which uncouples mitochondria).
Krebs cycle and ETC are running maximally. However, the link to ATP generation is broken so free energy released from substrates is released as heat).
Large increase in mitochondrial oxygen consumption after adding DNOC.
What is the metabolic effect of DNOC?
- DNOC and DNP can readily pass across inner mitochondrial membrane in their undissociated form.
- In the IMS, DNOC- + H+ —–> DNOC-H
- DNOC-H passes readily back through inner mitochondrial membrane to the matrix.
How can respiration rate and body temperature increase after using DNOC?
- Uncoupling of ATP synthase from ETC causes H+ accumulation in IMS.
- This potential energy released as heat
- Pulmonary ventilation rate increases - body trying to deliver more O2 so cells can respire to produce ATP
- Eventually organs failure causes death
How is rigor mortis caused by DNOC?
- ADP must be displaced by incoming ATP to relax muscles before next power stroke.
- DNOC poisoning means ATP conc decreases so contractile system remains contracted.
