Created: July 31, 2021
Modified: July 31, 2021
Modified: July 31, 2021
oxidative phosphorylation
This page is from my personal notes, and has not been specifically reviewed for public consumption. It might be incomplete, wrong, outdated, or stupid. Caveat lector.- This is how mitochondria produce most of their ATP.
- Mitochondria have an outer membrane and an inner membrane, so there are two chambers. The inner chamber is called the matrix. The citric acid cycle runs inside the matrix, producing NADH, among other things.
- There is a series of protein complexes embedded in the inner membrane wall (which is a lipid bilayer) which work to oxidize the NADH (and a proton) into NAD+ (and an H- plus the original proton), releasing energy. The spare electrons and protons eventually end up binding to oxygen to create H2O. This is called the electron transport chain. The energy released is used to pump protons outside of the matrix into the intermembrane space.
- These protons want to flow back into the matrix. The ATP synthase protein complex acts as a turbine powered by the flowing protons. On the inner end, it binds an ADP molecule and a phosphate group. As protons flow through it, the turbine spins, jamming the phosphate group onto the ADP to produce ATP, which then floats off, freeing up the binding site for another ADP. This is how most ATP is generated. Under optimal conditions, a glucose molecule creates 38 ATP, of which 30 come from oxidative phosphorylation (10 NADH creating 3 ATP each).
- Oxidative phosphorylation can also produce 'reactive oxygen species': O2 molecules with extra electrons. If there's one extra electron, this is called a superoxide; if there are two, it's a peroxide. Note that we'd need four extra electrons, plus protons from solution, to achieve the goal of forming two water molecules. Superoxides and peroxides are therefore oxidizers, since they'd prefer to steal more electrons to become water. It is hypothesized that cell damage caused by these species is a cause of aging.
- The drug 2,4-Dinitrophenol - Wikipedia disrupts oxidative phosphorylation by allowing protons to leak across the inner membrane, bypassing ATP synthase. This creates heat, and causes the body to raise its metabolism and burn fat to make up for the low efficiency. It is a very effective weight loss drug, but people have died using it.
- From comments on Shilling For Big Mitochondria - by Scott Alexander - Astral Codex Ten (substack.com): it's possible that reactive oxygen species are mostly created when the system gets 'backed up': there's a high proton gradient but no demand for ATP. So it's possible that 'mitochondrial uncoupling', aka allowing proton leakage, might reduce the formation of ROS.