Ox Phos Flashcards
What is Atractyloside and how does it impact oxidative phosphorylation?
Atractyloside is an inhibitor of the respiratory chain that looks similar to a purple artichoke with sweet roots. It poisons ADP/ATP antiporter, thus affecting the homeostasis of energy production during ox phos. “Triple AAA”
What kind of drug is Amytal and what are its effects?
Amytal is a barbiturate that is commonly used to treat anxiety and epilepsy. It is a reversible inhibitor of NADH dehydrogenase (Complex I of ETC). This blocks ETC to protect cardiac muscle and reduce ROS/ ischemia. “Amy’s #1”
What is Rotenone and its function on oxidative phosphorylation?
Rotenone is a natural pesticide or fish poison. It is a POTENT inhibitor of NADH Dehydrogenase (Complex I) that effective stops oxidation of NADH and reduces ATP levels. “Rotenone Reduces ATP”
Define Antimycin and its effects on ox phos.
Antimycin inhibits Complex III at its reduced state by binding TIGHTLY to Cytochrome b. This halts ATP production and REDUCES all the complexes before complex III (I, II and Q) and OXIDIZES all the complexes after (IV and Cyt c).
What affect does Cyanide have on oxidative phosphorylation that makes it so lethal?
Cyanide inhibits Complex IV of ETC by binding tightly to Fe3+ of Cytochrome oxidase (a3) at its oxidized state. This prevents O2 reduction (as final e- acceptor) and STOPS O2 consumption/ ATP production, leading to rapid cell death.
What can be used as immediate treatment against cyanide poisoning (if detected in time) and why?
A more powerful oxidizing agent will have to be inhaled then injected to convert Hb to metHb (oxidized form). MetHb has a HIGH affinity for cyanide to remove any form the blood so that it won’t bind to Cytochrome oxidase to further inhibit ATP production.
What is the only protein that interacts with Oxygen in ETC?
Cytochrome a3 within Complex IV is the only cytochrome to bind oxygen to reduce it to water.
What is Oligomycin and its effects on ox phos?
Oligomycin is an inhibitor of F(o) of ATP Synthase. This drastically increases the H+ gradient thus preventing ATP production and O2 consumption.
What is 2,4-Dinitrophenol? What symptoms might someone have from an overdose of this drug?
DNP is an uncoupled that works against the H+ gradient. Although ETC can still occur, energy linked with e- transport dissipates as HEAT. Some side effects include fatigue, high fever, hyperthermia and breathlessness (high respiratory rate).
What protein is known as a natural uncoupled of ETC? Where is it expressed?
Thermogenin (UCP-1) is a natural uncoupled expressed in brown fat that functions for whole body homeostasis and non-shivering heat generation.
What effect would Oligomycin coupled with DNP have on an aerobic cell?
Oligomycin and DNP would stop ATP production but still allow O2 to be consumed. The energy made from the cell will dissipate as heat.
What are the 2 ways that NADH can enter the mitochondria for ox phos?
- Malate-aspartate shuttle = works with high NADH/NAD+ ratio cytoplasm:mitochondria
- Glycerol Phosphate shuttle = FASTER although it produces less ATP.
Define the Malate aspartate shuttle.
Malate-aspartate shuttle transports cytoplasmic NADH into the mitrochondrial matrix if there’s a high NADH/NAD+ ratio. This is a reversible shuttle with no ATP loss that participates in ox phos in the liver, kidneys and heart. It releases oxaloacetate into the cytoplasm for gluconeogenesis.
Define the Glycerol Phosphate Shuttle.
This is an irreversible shuttle that participates in the skeletal muscle and brain. It uses FADH2 which costs ATP BUT is FASTER than the malate-aspartate shuttle. Glycerol-3-phosphate is the bypass reaction from glycolysis that is ALWAYS ON.
What is MELAS? Describe the symptoms associated with it.
Mitochondrial encephalomyopathy, lactic acidosis and stroke-like symptoms is the result of a mitochondrial gene mutation. This is caused from a mutation in Complex II of ETC leading to the impaired oxidation of succinate. It presents as muscle weakness and brain dysfunction.
