Effects of precursors on brain neurotransmitter synthesis and brain functions

Abstract

Abstract. This paper reviews factors which influence the levels of aminergic transmitters in the brain. In particular precursor availability to the brain influences the rates of synthesis of serotonin, the catecholamines, and acetylcholine by brain neurons. The diet readily influences brain neurotransmitter formation via this mechanism. At present, the importance of this relationship to body regulation is not well understood. Nonetheless, precursors (tryptophan, tyrosine, choline, and lecithin) have begun to find uses as therapeutic agents in the treatment of disease states involving diminished transmitter formation and release. Hopefully, these compounds will find a wide range of uses, as they lack many of the side effects that accompany the use of drugs.Key words: Tryptophan, tyrosine, choline, serotonin, catecholamines, acetylcholine, diabetes, blood pressure, pituitary hormones, neurologic disordersThe rates of synthesis of several brain neurotransmitters depend in part on the availability to neurons of the appropriate precursor molecules. Notably, the administration of tryptophan, tyrosine, or choline stimulates, under appropriate conditions, the formation of serotonin, the catecholamines, or acetylcholine, respectively. As a consequence, such treatments alter brain and body functions influenced by neurons utilizing these transmitters. In this article, the evidence supporting these precursor-product relationships will be reviewed, and several of the physiological-behavioral consequences will be discussed. SerotoninSerotonin (5-hydroxytryptamine; 5HT) iis synthesized from the essential amino acid L-tryptophan, by the two-step pathway outlined in Figure 1 (top panel). The first reaction, tryptophan hydroxylation, is rate-limiting [1]. Moreover, the rate of this reaction varies directly with brain tryptophan levels because the hydroxylase enzyme is not fully saturated with substrate at normal brain tryptophan concentrations [2]. Hence, acute (or chronic) increases in brain tryptophan elevate brain 5HT (and the levels of its principal metabolite, 5-hydroxyindoleacetic acid, 5HIAA), and decreases in brain tryptophan reduce brain 5HT and 5HIAA [3,4].Because changes in brain tryptophan are soon reflected as alterations in serotonin synthesis, factors that influence tryptophan uptake into brain should be potentially important determinants of brain 5HT formation. In normal animals, the single most important factor influencing tryptophan access to brain is the large neutral amino acid transport (LNAA) system, located at the blood-brain barrier [5]. Tryptophan is taken up into brain by this carrier system, as are other large neutral amino acids such as tyrosine, phenylalanine, and the branched-chain amino acids. The transport system is competitive [5]; as a consequence, tryptophan uptake into brain (and serotonin formation) depends not simply on blood tryptophan levels, but also on the blood levels of these other LNAA competitors. Brain tryptophan can be raised either by raising blood tryptophan, or by lowering blood ...

Reactive hypoglycemic tendency among arsonists

“…The great change in appetite found among group A arsonists also supports the hypothesis that brain serotonin may be involved (41,42). Insulin regulates the amount of tryptophan to enter the brain and thus also the serotonin metabolism (43)(44)(45). It thus seems possible that a low brain serotonin level and enhanced insulin secretion are somehow connected with the reactive hypoglycemic condition among hypoglycemic arsonists.…”

Quantification of the importance of individual steps in the control of aromatic amino acid metabolism

“…Thus variations in the time courses of, and sensitivity to, induction of the three enzymes [48][49][50] are not necessarily reflected in changes in the ratios of the amino acids in the blood. These ratios, and the absolute concentrations of the amino acids, are important determinants in the synthesis of biogenic amines in the brain [23][24][25], and it has been suggested that changes in the activities of the three liver enzymes may indirectly affect neurotransmitter synthesis through effects on removal of the amino acids from the blood [51,52]. Although changes in enzyme activity may indeed be of some significance, it now seems not improbable that competition for transport into the liver cell as well as into the brain [53,54] may be of equal importance.…”

“…The concentrations of the three aromatic amino acids in the blood and their ratios are important factors for neurotransmitter synthesis in the brain [23][24][25]. The activities of tryptophan 2,3-dioxygenase, phenylalanine hydroxylase and tyrosine aminotransferase change as the physiological and nutritional status changes, but not always in the same way and in parallel.…”

Behavioural Changes in Adult Rats Produced by Early Postnatal Maternal Deprivation and Treatment with Choline Chloride

“…In 1976, Cohen and Wurtman showed that dietary intake of choline for 3 to 11 days increases choline levels in the serum and acetylcholine levels in the brain of adult rats. The majority of studies could confirm these results (Ulus et al, 1978;Haubrich and Pflueger, 1979;Fernstrom, 1981;Domino et al, 1983) and only few experiments failed to register an increased brain acetyicholine content after exogenous choline administration (Eckernas, 1977;Flentge and van den Berg, 1979). Exogenous choline administration resulted in an increased ability of cholinergic neurons to synthesize acetyicholine, especially under conditions of increased neuronal demand (Schmidt and Wecker, 1981;Trommer et al, 1982).…”