Tissue-Specific Metabolism: The Division of Labor:- The Brain Uses Energy for Transmission of Electrical Impulses
The metabolism of the brain is remarkable in several respects. The neurons of the adult mammalian brain normally use only glucose as fuel (Fig. 1). (Astrocytes, the other major cell type in the brain, can oxidize fatty acids.) The brain has a very active respiratory metabolism (Fig. 2); it uses O2 at a fairly constant rate, accounting for almost 20% of the total O2 consumed by the body at rest. Because the brain contains very little glycogen, it is constantly dependent on incoming glucose from the blood. Should blood glucose fall significantly below a critical level for even a short time, severe and sometimes irreversible changes in brain function may result. Although the neurons of the brain cannot directly use free fatty acids or lipids from the blood as fuels, they can, when necessary, use β-hydroxybutyrate (a ketone body), which is formed from fatty acids in the liver. The capacity of the brain to oxidize β-hydroxybutyrate via acetyl-CoA becomes important during prolonged fasting or starvation, after liver glycogen has been depleted, because it allows the brain to use body fat as an energy source. This spares muscle proteins—until they become the brain’s ultimate source of glucose (via gluconeogenesis in the liver) during severe starvation. Neurons oxidize glucose by glycolysis and the citric acid cycle, and the flow of electrons from these oxidations through the respiratory chain provides almost all the ATP used by these cells. Energy is required to create and maintain an electrical potential across the neuronal plasma membrane. The membrane contains an electrogenic ATP-driven antiporter, the Na+ K+ ATPase, which simultaneously pumps 2 K+ ions into and 3 Na+ ions out of the neuron . The resulting transmembrane potential changes transiently as an electrical signal (action potential) sweeps from one end of a neuron to the other . Action potentials are the chief mechanism of information transfer in the nervous system, so a depletion of ATP in neurons has disastrous effects on all activities coordinated by neuronal signaling.
FIGURE 1 Energy sources in the brain vary with nutritional state. The ketone body used by the brain is β-hydroxybutyrate.
FIGURE 2 Glucose metabolism in the brain. The technique of positron emission tomography (PET) scanning shows metabolic activity in specific regions of the brain. PET scans allow visualization of isotopically labeled glucose in precisely localized regions of the brain of a living person, in real time. A positron-emitting glucose analog (2 [18F]-fluoro-2-deoxy-D-glucose) is injected into the bloodstream; a few seconds later, a PET scan shows how much of the glucose has been taken up by each region of the brain—a measure of metabolic activity. Shown here are PET scans of front-to-back cross sections of the brain at three levels, from the top (at the left) downward (to the right). The scans compare glucose metabolism (in mg/100 g/min) when the experimental subject (a) is rested and (b) has been deprived of sleep for 48 hours.
