It is proposed that severe impairment of liver function in cirrhosis or portacaval shunt results in unrestricted entry of insulin into the peripheral circulation. The ensuing high level of insulin promotes excessive removal of the branched-chain aminoacids by muscle, thereby lowering the plasma levels of these aminoacids. In consequence, the competitive action of the branched-chain aminoacids on the entry of tryptophan into the brain is reduced, more tryptophan enters the brain, and serotonin is synthesised in excess, thus facilitating hepatic coma.

Amino Acids↗

PubMed1975

Acute reduction of brain serotonin and 5-HIAA following food consumption: correlation with the ratio of serum tryptophan to the sum of competing amino acids.

In a series of experiments designed to test further our hypothesis that brain tryptophan and 5-hydroxyindole levels vary post-prandially as a function of the serum tryptophan to competitor ratio (i.e., ratio of serum tryptophan concentration to the sum of the concentrations of competing neutral amino acids), rats fasted overnight were allosed to consume for two hours single meals containing carbohydrates, fats, and various amino acids: Diet 1 contained no amino acids; Diet 2 contained five neutral amino acids known to compete with tryptophan for uptake into the brain; Diet 3 lacked tryptophan and the five competitors, but contained twelve non-neutral amino acids found in dietary protein; Diet 4 contained tryptophan and these same twelve non-neutral amino acids. The diet-induced modifications in brain tryptophan and 5-hydroxyindoles followed closely the changes in the serum tryptophan/competitor ratio, but not in serum tryptophan alone: The ingestion of Diet 4 raised serum tryptophan, but not the serum ratio, brain tryptophan or 5-hydroxyindoles; Diet 3 did not raise serum tryptophan, but did elevate the serum ratio, brain tryptophan and 5-hydroxyindoles. Diet 2 caused major reductions in serum tryptophan, the serum ratio, and brain tryptophan and the 5-hydroxyindoles. This diet might provide a simple, attraumatic means for lowering brain serotonin in studies of the physiology or serotonergin neurons. These studies provide further evidence that the effect of insulin on brain tryptophan uptake is not direct, but instead mediated via insulin-induced changes in the serum tryptophan/competitor ratio.

5-Hydroxytryptophan↗

PubMed1975

Control of brain monoamine synthesis by diet and plasma amino acids.

The rates at which monoaminergic neurons in rat brains synthesize their neurotransmitters depend on the availability of the amino acid precursors tryptophan (for serotonin) and tyrosine (for dopamine and norepinephrine). The administration of tryptophan, the injection of insulin, or the consumption of a single protein-free high-carbohydrate meal all elevate brain tryptophan levels and, soon thereafter, the levels of serotonin and its major metabolite 5-hydroxyindole acetic acid. The addition of protein to the meal suppresses the increases in brain tryptophan and serotonin, because protein contributes to plasma considerably larger amounts of the other neutral amino acids (e.g., leucine, phenylalanine) than of tryptophan, and these other amino acids compete with tryptophan for uptake into the brain. The elevation of brain tyrosine (by injection of the amino acid or consumption of a single 40% protein meal) accelerates brain catecholamine synthesis, as estimated by measuring brain dopa accumulation after decarboxylase inhibition, or brain catecholamine accumulation after inhibition of monoamine oxidase. These observations suggest that serotonin- and catecholamine-containing brain neurons are normally under specific dietary control.

Amino Acids↗

PubMed1975

Effects of skim milk, whole milk and light cream on serum tryptophan binding and brain tryptophan concentrations in rats.

One hour after rats fasted for 13 hours consume a single meal of skim milk, whole milk, or light cream, serum nonesterified fatty acid (NEFA) concentrations changed in direct proportion to the fat content of the diet: serum NEFA levels decreased in rats ingesting skim milk (0.09% fat) to 34% of fasting control values; in animals consuming whole milk (3.59% fat), levels dropped to 50% of fasting levels; these levels did not change significantly, however, in rats consuming light cream (18.26% fat). The percentages of total serum tryptophan not associated with albumin in rats ingesting skim milk, whole milk, or light cream were 22.2, 26.0, and 42.5%, respectively. These variations in serum free tryptophan were not accompanied by significant differences in brain tryptophan among the three treatment groups. These results thus confirm that, with a natural food source, (a) postprandial serum NEFA levels reflect the total fat content of the diet; (b) serum free tryptophan concentration shift proportionately with serum NEFA; and (c) serum free tryptophan concentrations do not reliably predict brain tryptophan levels.

Animals↗

PubMed1975

Effects of ingestion of a carbohydrate-fat meal on the levels and synthesis of 5-hydroxyindoles in various regions of the rat central nervous system.

Explore the source record for details and available documents.

5-Hydroxytryptophan↗

PubMed1975

The mechanism by which methiothepin, a putative serotonin receptor antagonist, icnreses brain 5-hydroxyindole levels.

Brain tryptophan and 5-hydroxyindole levels are elevated in rats given methiothepin, a neuroleptic that appears to block serotonin receptors. The rise in brain tryptophan probably results from a drug-induced increase in the ratio of plasma tryptophan concentration to the sum of the neutral amino acids in plasma that compete with tryptophan for uptake into the brain; this change in the plasma amino acid pattern may be mediated in part by a methiothepin-induced rise in plasma insulin. Methiothepin also decreases the proportion of circulating tryptophan that is bound to albumin. Unlike exogenous tryptophan, methiothepin fails to increase 5-hydroxyin-doles caudal to the site of a spinal cord transection. Therefore, the mechanism by which methiothepin elevates 5-hydroxyindole levels involves not only increased brain tryptophan levels but also continued impulse flow along serotonergic neurons.

Amino Acids↗

PubMed1974

Diazepam increases 5-hydroxyindole concentrations in rat brain and spinal cord.

Explore the source record for details and available documents.

Animals↗

PubMed1974

Brain catechol synthesis: control by train tyrosine concentration.

Brain catechol synthesis was estimated by measuring the rate at which brain dopa levels rose following decarboxylase inhibition. Dopa accumulation was accelerated by tyrosine administration, and decreased by treatments that lowered brain tyrosine concentrations (for example, intraperitoneal tryptophan, leucine, or parachlorophenylalanine). A low dose of phenylalanine elevated brain tyrosine without accelerating dopa synthesis. Our findings raise the possibility that nutritional and endocrine factors might influence brain catecholamine synthesis by controlling the availability of tyrosine.

Alanine↗

PubMed1974