Re: Can brain cells metabolize via fermentation like muscle cells do?

Brain cells are capable of glycolytic fermentation when the oxygen tension of the mitochondria drops sufficiently to slow oxidative phosphorylation (<1 mm Hg). This is the matter of respiratory stress. If the entry of pyruvate into the tricarboxylic acid cycle is decreased, then pyruvate is shunted to the end product of lactate via pyruvate dehydrogenase. It is typically taught that pyruvate dehydrogenase is lacking, but the activity is present in low levels so that a serious backup in the TCA cycle is needed to produce pyruvate concentrations sufficient to result in lactate.

In essence, glycolysis is not efficient enough to supply the ATP needed by brain cells during normal function (2 ATP per glucose) compared to oxidative phosphorylation (40 ATP per glucose). The detriment to neurons is that as much as half the ATP produced by normal respiration may be consumed simply to maintain the transplasmalemma sodium ion gradient. If the gradient collapses, then the cells will swell osmotically, lyse, fill with calcium ions, and die.

Therefore, considerable physiological mechanisms have evolved in the brain and central nervous system to recover from respiratory stress. It has been found that, in generating a drive to the respiratory muscles of the diaphragm and the intercostal muscles of the ribs, brain cells are capable of responding only to their ambient pH. Although peripheral mechanisms exist to detect the oxygen tension of the blood directed toward the brain, the only internal sensing mechanism the brain uses is for pH. When oxygen to the brain is deprived, and the cells shift to glycolysis, the resulting decrease in ambient pH results in massive afferent volleys to the pontine and medullary areas containing the respiratory control rings of neurons that results in more impulses during each burst conveyed by the phrenic nerve.

In some individuals with metabolic disorders, such as diabetes, the acetaldehyde produced by pyruvate dehydrogenase reaches sufficiently high concentration to enable the low activity of alcohol dehydrogenase to shunt the acetaldehyde to ethanol, just as in yeast.

A good comprehensive reference for understanding the metabolism of the brain is Vernon B. Mountcastle's multi-volume text titled Medical Physiology.