Oxidative phosphorylation · Grey Matter

Oxidative phosphorylation is the process in the mitochondria that uses oxygen to make most of a cell's ATP, the molecule that pays for the pumps, and in the brain it supplies nearly all the energy behind every signal.

Oxidative phosphorylation. Oxidative phosphorylation is the process in the mitochondria that uses oxygen to make most of a cell's ATP, the molecule that pays for the pumps, and in the brain it supplies nearly all the energy behind every signal.

ATP (adenosine triphosphate) is the cell's energy currency: splitting off its last phosphate releases energy that enzymes such as the sodium-potassium pump use directly. To make it, pyruvate from glycolysis is oxidised in the mitochondrial matrix by the citric acid cycle, which strips its electrons onto carriers (NADH and FADH2) and releases carbon dioxide. The electron transport chain in the inner membrane passes those electrons down a series of proteins, using their energy to pump protons out of the matrix; at the end of the chain oxygen accepts the electrons and becomes water. The protons flow back through ATP synthase, a rotary enzyme that makes ATP as they pass.

The yield is about 30 to 32 ATP per glucose in total, in current estimates (older textbooks say 36 to 38, based on assumptions about how many ATP each NADH yields that later measurements lowered). Glycolysis gives 2 of these; nearly all the rest come from oxidative phosphorylation.

Oxygen is the last link. Without it the chain stops, protons are no longer pumped, and ATP production collapses to the small glycolytic share; that is why the brain fails within seconds to minutes of losing its blood supply (see ischaemic cascade).

Neurons depend on it heavily. Mitochondria cluster at synapses and nodes, where pumps work hardest, and failing mitochondria are a common thread in neurodegenerative disease.

Oxygen is the brain's real fuel limit.

Glucose can be stored elsewhere in the body, but only a continuous stream of oxygen lets the mitochondria turn it into enough ATP to keep the gradients charged.

Questions: What does oxygen actually do in a neuron, and why does losing it stop the brain within seconds? Oxygen accepts the electrons at the end of the mitochondrial transport chain and becomes water; that last step keeps the chain moving, the chain pumps protons, and the proton flow drives ATP synthase. Without oxygen the chain jams within moments, and the brain has almost no stored oxygen and little stored fuel to fall back on. When blood flow stops completely, consciousness is lost in about 10 seconds and the EEG flattens within about 20 to 40 seconds, as neurons go quiet to save energy. Over the following minutes ATP runs out, the pumps fail and the ion gradients collapse, which starts the damage. How much ATP does one glucose give, and why does the brain need oxygen to get it? Glycolysis, in the cytoplasm and without oxygen, splits glucose into two pyruvates for a net gain of 2 ATP. Oxidising those pyruvates completely in the mitochondria, through the citric acid cycle and the electron transport chain, brings the total to about 30 to 32 ATP per glucose, by current estimates (older textbooks say 36 to 38, from higher assumed yields per NADH). Oxygen is the final acceptor of the electrons in that chain, so without it the mitochondria stop and the cell is left with the glycolytic 2. For an organ that spends its energy as fast as the brain does, a fifteenfold difference in yield is the difference between working and failing.