Macronutrients and neurotransmitter formation during brain development

摘要

L-tryptophan (L-Trp) is an essential amino acid and the precursor for the biosynthesis of brain serotonin. Various experimental nutritional changes alter the level of plasma and brain L-Trp. There are two known fractions of plasma L-Trp, one bound to albumin, and another free. The free fraction traverses the blood-brain barrier (BBB) where it is taken up by serotonin (5-HT) neurons to activate synthesis of the neurotransmitter 5-HT. There are several possible mechanisms proposed for the regulation of the amount of plasma L-Trp passing to the brain. One is a specific transport system and another is that the amount depends on its not binding to albumin. These two mechanisms may compete at the BBB level; it is possible that the higher affinity of the carrier system at the brain capillary wall would strip L-Trp from albumin and increase its transport to the brain. A third regulator would be through the competition of the neutral amino acids (Phenylalanine, Valine, Leucine, Tyrosine, Isoleucine), which seem to share the carrier that transports L-Trp to the brain. In the brain, L-Trp is hydroxylated in serotonergic neurons by the action of the enzyme tryptophan hydroxylase (EC 1.14.1 6.4, TrpOH). 5-Hydroxytryptophan is then decarboxylated to 5-HT. We have reported that in rats malnourished during gestation or lactation, there is accelerated synthesis of brain 5-HT; it starts in the fetal period and coincides with an increase of brain L-Trp and the activity of TrpOH, suggesting that an activation of the serotonergic system occurs during this period of nutritional stress.