Neurotransmitter Precursors

Precursor Loading A nutrient is a food substance that in most cases supplies either the energy or the molecular building blocks the body requires. A drug is a substance given for its effect on a specific organ or type of cell. All healthy people need essentially the same nutrients - a drug would ordinarily be recommended only for people with a particular disease or condition. There are several nutrients that- when they are administered in the pure form or even simply ingested in food can act like drugs. They give rise to important changes in the neural activity in the brain. Two of the nutrients are the amino acids tryptophan and tyrosine. Amino acids are the building blocks of proteins and so tryptophan and tyrosine are present in foods. The neuronutrient food and hence- the makeup of the brain can be altered by tryptophan, tyrosine and choline because they are the precursors of neurotransmitters substances that are released from a neuron or nerve cell when it fires. The neurotransmitter thereby conveys the nerve impulse across a synapse to either another neuron, a muscle cell or a secretory cell. Tryptophan is converted in the terminals of certain neurons into the neurotransmitter serotonin. In still another population of cells tyrosine serves as the precursor of dopamine, norepinephrine and epinephrine which are called the catecholamine neurotransmitters. An increase in the brain level of a precursor enhances the synthesis of the corresponding neurotransmitter product. The enhanced synthesis can in turn cause the neuron to release more transmitter molecules when it fires amplifying the transmission of signals from the neuron to the cells it is connected to. The conversion of tryptophan into serotonin is influenced by the proportion of carbohydrate in the diet . The synthesis of serotonin in turn affects the proportion of carbohydrate an individual subsequently chooses to eat. In the case of choline and tyrosine the effect on a neuron of an increased supply of the nutrient both varies with the neuron's firing frequency and can lead to changes in that frequency. Choline and tyrosine can therefore amplify neurotransmission selectively increasing it at some synapses but not at others. These natural food-agents may be able to help treat several diseases including hypertension, some forms of depression, Parkinsonism and some memory disorders of old people. Daily rhythms in the metabolism of dietary amino acids prompted some discoveries. For people who eat at the usual times plasma amino acid levels generally exhibit pronounced daily rhythms. For example among people consuming a typical high-protein American diet the plasma concentration of the amino acid leucine is twice as high in the early evening and night as it is during the rest of the day. If the same people eat protein-free meals the leucine level instead falls by half during these hours of active digestion and absorption. In the first case the increase represents the entry into the bloodstream of some of the leucine in the dietary protein. In the second case the decrease results from the secretion of insulin induced by ingested carbohydrate which accelerates the passage of leucine and most other amino acids from the circulation into skeletal muscle. In order for changes in the level of a nutrient to influence the rate of conversion the enzyme catalyzing the conversion must have a certain property. The enzyme's ability to bind the nutrient preparatory to changing its chemical structure must be relatively poor so that at the usual nutrient concentrations each enzyme molecule is less than fully saturated with the nutrient and functions at less than peak efficiency. In this situation the quantity of the nutrient available to the enzyme is the rate-limiting element in the reaction and so an increase in the nutrient's concentration increases the level of enzyme activity more of the nutrient is converted and more of the product is formed. The release of serotonin by neurons originating in the brain stem delivers signals to widely scattered groups of neurons that control such things as sleep,mood and appetite. Investigators have shown that the concentration of serotonin in the brain can be increased by giving experimental animals very large doses of pure tryptophan. Normal daily variations in the plasma concentration of tryptophan might be enough to alter the rate of serotonin synthesis in the rat brain. Even low doses of tryptophan which raise the plasma concentration of the amino acid but keep it within the normal daily range do enhance serotonin synthesis. Rats injected with insulin surprisingly did not lower the tryptophan concentration in the plasma and it actually raised the concentration in the brain in creasing serotonin synthesis. Large amounts of protein surprisingly (even though amino acids are plentiful in the diet) reduce both the brain concentration of tryptophan and the synthesis of serotonin . The apparent paradoxes is because the amount of tryptophan available in the brain for conversion into serotonin depends not only on the amount of tryptophan in the plasma but also on the ratio of plasma tryptophan to the plasma level of five other amino acids tyrosine, phenylalanine, leucine, isoleucine and valine. All six of these amino acids are comparatively large molecules and in a physiological environment most of them are electrically neutral with about as much positive charge as negative. Their passage between the blood and the brain is facilitated by carrier molecules present in the endothelial cells lining brain capillaries. A single species of carrier molecule transports all six of the large neutral amino acids across the blood-brain barrier. The amino acids compete with one another for attachment to the carrier and hence for uptake from the bloodstream into the brain. There is far less tryptophan in most proteins than there is tyrosine, phenylalanine,leucine isoleucine or valine. A high-protein evening meal therefore reduces the plasma ratio of tryptophan to the competing amino acids so less tryptophan is carried across the barrier and less reaches the neurons. Conversely, a high carbohydrate meal in the evening tends to increase serotonin utilization levels.