Glycolysis · Grey Matter

Glycolysis is the first stage of burning glucose, ten reactions in the cytoplasm that split one glucose into two pyruvates and yield a net 2 ATP, and in the brain it is the fast, oxygen-free start of an energy supply that is completed in the mitochondria.

Glycolysis. Glycolysis is the first stage of burning glucose, ten reactions in the cytoplasm that split one glucose into two pyruvates and yield a net 2 ATP, and in the brain it is the fast, oxygen-free start of an energy supply that is completed in the mitochondria.

Glucose reaches the brain from the blood through the transporter GLUT1 in the endothelial cells of the blood-brain barrier and in astrocytes, and enters neurons mainly through GLUT3, a higher-affinity transporter. Inside the cell, glycolysis invests 2 ATP and recovers 4, for a net gain of 2, plus 2 NADH carrying electrons. What happens to the pyruvate decides the rest of the yield. With oxygen available, most enters the mitochondria and is oxidised completely by the citric acid cycle and oxidative phosphorylation, for about 30 to 32 ATP per glucose in total; without oxygen, or when glycolysis runs faster than the mitochondria, pyruvate is turned into lactate so that glycolysis can continue.

It is fast and local. Glycolytic enzymes sit close to the pumps in the membrane and respond within moments to a sudden demand, which makes glycolysis well suited to brief bursts of activity.

The brain uses some of it without oxygen even when oxygen is present. Activated areas take up glucose a little faster than they consume oxygen (aerobic glycolysis), and part of the extra becomes lactate, which may be shuttled between cells (see lactate shuttle).

Red blood cells run on glycolysis alone, having no mitochondria; neurons cannot, and fail within minutes on glycolysis by itself.

Glycolysis is the brain's quick cash, oxidation its salary.

It gives energy at once without oxygen, but at a fifteenth of the yield, so a brain cut off from oxygen runs out within minutes.

Questions: What does the brain run on during a long fast? At first on glucose, released from the liver's glycogen and then made from amino acids and glycerol. As the fast continues, the liver converts fat into ketone bodies (beta-hydroxybutyrate and acetoacetate), their blood level rises, and the brain takes them up and burns them in its mitochondria. In the classic measurements of Owen and colleagues (1967), after five to six weeks of starvation ketones supplied about 60 % of the brain's energy, and up to about two thirds by other estimates. This spares muscle protein that would otherwise be broken down to make glucose, while the brain keeps a smaller but necessary glucose supply. 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.