In Biochemistry, we are going over several different metabolic pathways, and I h
ID: 215361 • Letter: I
Question
In Biochemistry, we are going over several different metabolic pathways, and I have a question regarding Oxidative Phosphorylation. We learned about inhibitors and uncouples in the electron transport chain that prevents oxidative phosphorylation by inhibiting ATP synthase. From my understanding, the ETC will still work, but ATP cannot be generated because ATP synthase is compromised. First, how exactly is ATP synthase inhibited?
Also, we learned about regulated uncoupling in “brown fat” in the body. My question is: are there any benefits/reasons why we need to uncouple the ETC from ATP synthase? To me, it seemed like it would only have negative effects, but if it’s regulated in the body, there must be some significance to it? I have read my professors lecture slides as well as read in my book about it, but I can’t get it to click in my head. Much thanks!
Explanation / Answer
Not all uncouplers directly inhibit ATP synthase. The mechanism of action of different uncouplers is given below:
Amytal or amobarbital is an insecticide, which blocks the electron transport chain (ETC) by preventing the utilization of NADH (inhibits between NADH and Co-enzyme Q). Electron flow that occurs from the oxidation of respiratory complex II is unaffected by amytal, means succinate co not accumulate. The respiratory depression caused by amytal is mainly due to depression of respiratory center.
Cyanide binds to the ferric ions and inhibits the heme to bind to cytochrome oxidase, which blocks the ETC by the inhibition of redox reactions. No proton pumps function and no ATP is synthesized, this results in decreased oxygen consumption.
2,4-dinitrophenol (DNP) is an uncoupler that acts as a proton ionophore. This is a highly fat-soluble compound, which bound to the protons on one side of the membrane, and releases them on the other side. So, the proton gradient cannot be maintained, the oxygen consumption and ATP production decrease.
The two probable advantages of cellular uncouplers are,
1. Thermogenesis (at the organism level)
2). Reducing the production of reactive oxygen species (ROS), thus, reducing the oxygen damage
Both of these can be considered as adaptive mechanisms of an organism, but it also increases the susceptibility to necrotic death.