Figure 2.

Glucose, which is the major fuel in the brain, is transported across the cell membranes by facilitated diffusion mediated by glucose transporter proteins (GLUT). Two types of glucose transporters (sodium dependent and facilitative transporters) are localized in the membranes of neurons, astrocytes and brain endothelial cells. Of these, GLUT-1 and GLUT-3 represent the two most important transporters in the brain. Under normal conditions, pyruvate is formed from glucose after entering the glycolytic process generating two molecules of ATP. Subsequently, it enters the citric acid cycle if oxygen is available, yielding 32 ATP molecules. During a state of cerebral hypoxia and low glucose (e.g., intracranial hypertension) the production of ATP from the citric acid cycle decreases. Then, cells attempt to compensate for the decrease in ATP production by increasing the turnover of glucose in the anaerobic part of the glycolysis. During this process it is necessary to regenerate NAD+ from NADH, which facilitates maintenance of glycolysis. The NAD+ regeneration causes an increase in lactate and the lactate/pyruvate ratio. The ratio is essentially the same in all tissues (i.e., about 20). A ratio above 25 is considered as an early warning of beginning metabolic crises.