The support of energy metabolism in the central nervous system with substrates other than glucose

The brain is extremely active metabolically, with its local energy demands fluctuating rapidly between high and low activity states. However, the brain-fs endogenous energy stores are small. Consequently, normal brain function requires a continuous supply of exogenous substrates obtained via the bloodstream. Under normal physiological conditions, glucose is the dominant exogenous energy substrate in the adult brain (Clarke and Sokoloff, 1999). Glucose is transported into the brain via glucose transporters located in the endothelial cells of the blood.brain barrier (BBB) (Clarke and Sokoloff, 1999). A favorable concentration gradient drives this transport given that blood glucose is about 5.7 mM (Ruderman et al., 1974; Hasselbalch et al., 1994) and glucose in the extracellular space of the brain is about 1-2 mM (Silver and Erecinska, 1994; Pfeuffer et al., 2000) (see > Table 2.1-1). An ample supply of glucose and tight regulation of glycolysis by the prevailing cellular energy status allows brain cells to respond quickly to fluctuations in energy demands (Chih and Roberts, 2003). However, other exogenous or endogenous energy substrates can serve as alternatives to glucose under certain physiological or pathological conditions.