The nerve impulse is initiated by the depolarization of the neuronal plasma membrane. This depolarization releases potential energy earlier established through the formation of transmembrane ion gradients. The amount of energy released by depolarization is fixed, so to obtain an increase in signal intensity, an increase in the frequency sufficient to re-establish the ion gradient is necessary. For this purpose, chemical energy in the form of adenosine-5'-triphosphate (ATP) is needed, in an amount at least equal to the potential energy that will be consumed in the next depolarization .
The increased neuronal ATP generation creates a demand for increased availability of oxidizable substrates and increased activity of cellular mechanisms to enable its utilization. Several substrates, such as glucose, ketone bodies (b-hydroxybutyrate and acetoacetate) or free fatty acids (FFA), can be used to produce the necessary ATP for neuronal activation depending on substrate availability and the kinds of cells involved.
Another important metabolic aspect of neuronal cell function is the storage and timely release of neurotransmitters upon receipt of signals, functions which require intense membrane fatty acid synthesis and turnover. Insulin production exemplifies the importance of neuropeptides in regulating de novo fatty acid synthesis and turnover in differentiating islet beta cells as outlined later in this review. Glucagon-like peptide-l (GLP-1) is a powerful neuropeptide regulating beta cell de novo fatty acid synthesis and turnover with a primary effect of increasing glucose carbon channeling towards fatty acid synthesis, chain elongation and desaturation of the long chains. Further explorations of these unique metabolic effects of hormones acting in the brain, for example, GLP-1, improve the understanding of neuronal response and neurological and psychiatric diseases and lead to the discovery of new target sites for drug interactions with molecular mechanisms responsible for defective neurotrans-mitter synthesis and responses.
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