Neurodining: Common dietary factors may be substrates in novel biosynthetic pathways for monoaminergic neurotransmitters

Abstract

It is not established that there are multiple endogenous mechanisms for synthesizing each of the three major monoamine neurotransmitters: serotonin, norepinephrine, and dopamine. Having multiple biosynthetic pathways for each of these important signaling molecules would provide greater assurance that they are available in sufficient quantities for their various physiological roles in the body. This paper puts forth the hypothesis that a number of common dietary factors-including sucrose and glucose, fats, plant components, and even ethanol-are substrates in novel biosynthetic pathways for the monoamines. A major aspect of this hypothesis is that in a range of multicellular organisms, D-glucose in particular may participate in novel biosynthetic pathways for the monoamines, where this sugar has already been linked with synthesis of the neurotransmitters acetylcholine, glutamate, and GABA through the tricarboxylic acid cycle. Another major aspect of the hypothesis is that phenol or polyphenol molecules, found in various plants, may combine with particular fats or even ethanol to form dopamine, which can then be converted to norepinephrine through the already established step involving the enzyme dopamine beta-hydroxylase. If such a biosynthetic pathway exists for converting ethanol to dopamine in humans, it could be a major factor in substance abuse, including early onset alcoholism. Further, if the above biosynthetic pathways exist in a range of organisms, they may be associated with appetitive processes regulating consumption of particular dietary factors, such as fruits and vegetables, to maintain internal "set points" of, for example, elevated noradrenergic signaling. In this scenario, exposure to psychological stress, which could eventually deplete neurotransmitters such as norepinephrine, may result in craving for sucrose, fats, or alcohol to help replenish the depleted cellular levels of this signaling molecule. An alternative to the overall biosynthetic hypothesis put forth here is that animal cells do not possess these pathways, but the animal microbiome harbors bacteria that do carry out these reactions and helps supply the body with monoamines and other signaling molecules.