Chapter 46: Metabolism of the Nervous System

The nervous system comprises neurons and specialized glial cells including astrocytes, oligodendrocytes, Schwann cells, microglia, and ependymal cells, each fulfilling distinct roles in neural support, energy provision, structural maintenance, and immune defense. Neurons communicate through action potentials and synaptic transmission, while glial populations regulate extracellular ion concentrations, supply metabolic substrates such as lactate, and facilitate tissue repair and regeneration. The blood-brain barrier maintains selective permeability to glucose, ketone bodies, essential fatty acids, and large neutral amino acids while blocking harmful substances and unnecessary lipids; dysfunction exemplified by GLUT1 deficiency syndrome results in seizures and developmental impairment, often managed through ketogenic diet intervention. The brain's extraordinary metabolic demand creates vulnerability to glucose deprivation and oxygen deficiency, conditions that impair neurotransmitter production, trigger excitotoxic cascades mediated by glutamate excess, and precipitate encephalopathy or cerebrovascular accidents. Catecholaminergic metabolism converts tyrosine through L-DOPA into dopamine, norepinephrine, and epinephrine under control of tyrosine hydroxylase, with inactivation accomplished by monoamine oxidase and catechol-O-methyltransferase. Serotonin synthesis from tryptophan regulates mood, appetite, and circadian function, while melatonin coordinates sleep-wake cycles. Histamine derived from histidine mediates allergic responses peripherally and functions as an excitatory neurotransmitter centrally. Acetylcholine synthesis from acetyl-CoA and choline operates at neuromuscular junctions but remains susceptible to neurotoxins including sarin gas. Excitatory amino acid neurotransmitters glutamate and aspartate contrast with inhibitory transmitters GABA and glycine; imbalances precipitate seizure disorders and psychiatric disease. Nitric oxide functions distinctively as a gaseous retrograde messenger regulating vascular dilation and neural signaling. Lipid metabolism in the central nervous system depends largely on local synthesis due to blood-brain barrier restrictions, with peroxisomal and lysosomal dysfunction causing severe neuropathies such as Refsum disease and mucopolysaccharidoses. Myelin composition emphasizes galactocerebrosides and cholesterol supported by structural proteins including proteolipid protein and myelin basic proteins in the central nervous system and P0 protein in the peripheral nervous system; demyelinating diseases like multiple sclerosis and hereditary neuropathies such as Charcot-Marie-Tooth disease highlight myelin's critical role in rapid conduction velocity.