Plasma Free Tryptophan Research Articles

Regional Brain Variations of Tryptophan, Monoamines, Monoamine Oxidase Activity, Plasma Free and Total Tryptophan during the Estrous Cycle of the Rat

Normal 4-day cyclic rats were sacrificed at 10 a.m. and 3 p.m. on proestrus or estrus and at 10 a.m. on metestrus. Noradrenaline (NA), dopamine (DA) and tryptophan (T) concentrations varied only slightly. Serotonin (5-HT) concentrations showed characteristic changing patterns in many hypothalamic, limbic and midbrain structures with a decrease during proestrus and an increase during estrus being observed. Monoamine oxidase (MAO) activity changes were often parallel to the 5-HT changes, but were not as great. The marked changes in 5-HT early in proestrus are a further indication of its inhibitory effect on gonadotropin release mechanisms before the 'critical period'.

Salicylate, tryptophan, and tyrosine hypothermia.

The intraperitoneal administration of sodium salicylate, L-tryptophan, and tyrosine resulted in significant hypothermia when rats were exposed to a 4degree C ambient temperature. Salicylate and tryptophan increased plasma levels of nonprotein-bound tryptophan while total and bound tryptophan were reduced in salicylate-treated rats. Tryptophan concentrations were unaffected by tyrosine administration. Concomitant with increases in free plasma tryptophan, there occurred significant rises in brain levels of tryptophan in both groups of rats, while brain tyrosine levels were increased in those rats receiving tyrosine. Similarly, significant increments in hypothalamic serotonin levels in rats receiving salicylate or L-tryptophan and increases in hypothalamic norepinephrine in tyrosine-treated rats seem to reflect the increased availability of tryptophan and tyrosine for monamine synthesis. However, alternative mechanisms of hypothermiaseem to be operative since oxygen consumption studies demonstrate dissimilar results for tryptophan and salicylate administration.

Tryptophan and tyrosine disposition and brain tryptophan metabolism in acute carbon tetrachloride poisoning

Forty-eight hours after injecting rats with carbon tetrachloride there were large increases of plasma non-esterifed fatty acid and free tryptophan concentrations. Total plasma tryptophan was not significantly altered. Brain, liver and muscle tryptophan concentrations increased significantly with percentage changes in the order: brain > liver > muscle > kidney. The increased brain tryptophan was associated with a small but significant increase of 5-hydroxytrptamine and a larger increase of its metabolite 5-hydroxyindolylacetic acid. Tyrosine concentrations increased significantly in plasma, brain, liver, muscle and kidney with percentage changes in the same order as those of tryptophan. Food intake was decreased and this correlated significantly with brain tryptophan and 5-hydroxyindolylacetic acid concentrations. Control rats kept for 48 hr on restricted intake did not show the above brain changes though plasma non-esterified fatty acid concentration was increased as in the drug treated rats. Results are discussed in relation to previous findings in acute liver failure and to the possible roles of brain tryptophan and 5-hydroxytryptamine in liver failure and appetite control.

Glutamic acid and tryptophan additions to a low-protein pig starter.

Two feeding trials with baby pigs were conducted to evaluate the effects of additions of L-tryptophan and L-glutamic acid to a low protein (16%) starter diet on performance and plasma urea nitrogen, α-amino nitrogen and free tryptophan. In experiment 1, but not in experiment 2, glutamic acid addition (3.36%) improved rate of gain and feed efficiency. Tryptophan addition did not improve performance in either experiment. Plasma tryptophan data in both experiments indicated that the tryptophan level and availability were adequate in the low-protein diet. The response to glutamic acid suggests inadequate levels of dispensable amino acids for the baby pig in the low-protein basal diet.

The effects of diet, lipolysis and limb ischaemia on the distribution of plasma tryptophan in the rat

A non-linear relationship between the plasma non-esterified fatty acid concentration and the percentage of free plasma tryptophan was found in rats in different nutritional states, although non-esterified fatty acids are not the only factors determining the percentage of free tryptophan. This relationship was not seen in rats injured by limb ischaemia. The effect of drugs causing rapid increases in the plasma non-esterified fatty acid concentration was also studied. Isoprenaline decreased the total plasma tryptophan concentration. Dichloroisoprenaline caused a sustained increase in the plasma non-esterified fatty acid concentration which was accompanied by an increase in the concentration of free plasma tryptophan and followed by a fall in the concentration of total tryptophan. The loss of tryptophan from the plasma was attributed to an altered distribution of tryptophan in the extracellular space rather than to increased metabolism. This interpretation was supported by determinations of the irreversible disposal rate of plasma tryptophan which in uninjured rats was unaffected by the concentration of free plasma tryptophan. In the injured rats this rate was unaltered during limb ischaemia but was decreased after removal of the tourniquets; increased competition for tissue entry by other neutral amino acids and the fall in body temperature could be factors in this fall.

Correlations between circadian changes in serum amino acids or brain tryptophan and the contents of serotonin and 5-hydroxyindoleacetic acid in regions of the rat brain

Circadian changes in tryptophan, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were investigated in the cerebral cortex and the brain stem of male Sprague-Dawley rats previously exposed to a 14:10 light-dark (LD) lighting regimen. Control rats were provided food and water ad libitum while experimental rats were given food daily only between 10.00 and 14.00 h. Statistically significant circadian changes in 5-HIAA were observed in the cerebral cortex of the control and the experimental animals and in the brain stem of the experimental animals. Circadian changes in tryptophan were observed in the cortex and brain stem of control animals, but the magnitude of the daily changes in tryptophan in experimental animals was comparatively reduced so that a statistically significant change was observed only in the brain stem. Highly statistically significant correlations were demonstrated between brain tryptophan and 5-HIAA suggesting a possible interrelationship between these parameters. Circadian changes in 5-HT were observed in the cerebral cortex of the experimental and in the brain stem of control animals. The inconsistency of the 5-HT rhythms may be a reflection of the daily disturbance of the animals. Significant circadian changes in free and also total plasma tryptophan were observed in both the control and experimental animals. Levels of 5-hydroxyindoleacetic acid or tryptophan in the brain were not consistently correlated with free plasma tryptophan or free plasma tryptophan/tyrosine in either control or experimental rats.

Monoamine oxidase and free tryptophan in human plasma: normal variations and their implications for biochemical research in affective disorders.

A methodological study of healthy subjects was conducted to investigate factors influencing plasma free tryptophan and platelet monoamine oxidase (MAO) activity. The following changes were found during the menstrual cycle: free tryptophan was lower during the "ovulatory" phase than during the "premenstrual" phase, MAO activity was 20% lower during the "premenstrual" phase as compared with the "neutral" phase (days: menses-24 to -1). During pregnancy MAO activity was also lower than the values found six weeks postpartum. MAO activity in women was significantly higher than in men and exhibited greater variability. A circadian rhythm for free tryptophan was observed (minimum at midday, maximum at midnight). No diurnal variation in MAO activity could be established. Preliminary data from untreated endogenous depressive patients showed no difference in free tryptophan concentrations at 8 a.m. or 4 p.m. from control values.

Plasma tryptophan and sheep.

Free, bound, and total plasma tryptophan (F.P.T., B.P.T., and T.P.T.) levels have been measured throughout the night in six young female volunteers. All-night polygraphic sleep recordings were also made. No direct temporal relationship was found between plasma tryptophan levels and specific sleep stages. The mean F.P.T. levels, however, were found to have a positive correlation with rapid-eye-movement (R.E.M.) sleep and a negative correlation with non-R.E.M. sleep. An inverse relationship existed between the F.P.T. and B.P.T. levels. There appeared to be a diurnal variation in F.P.T. levels, with high readings in the first half of the night.

Plasma and Tissue Free Amino Acid Concentrations in Rats Fed Tryptophan-imbalanced Diets with or without Niacin

The concentration of free tryptophan and other free amino acids in blood plasma and of free tryptophan and threonine in liver and muscle have been determined in rats fed tryptophan-imbalanced diets ( induced with 7.8% amino acids in a low protein adequate-niacin diet or with threonine or 2.06% amino acids in a low protein niacin-free diet). The concentration of free tryptophan in the plasma and liver of rats fed the threonine-induced niacin-deficient diet was not depressed below that of the control animals. However, tryptophan concentration decreased in the plasma of rats fed the above diet corrected with 2.5 mg nicotinamide/100 g diet. Liver tryptophan concentrations, however, did not decrease in the niacin-corrected group. The only prominent change in other amino acids was that of threonine, which increased markedly in all groups supplemented with threonine. When the 7.8% amino acid-induced un balanced diet containing adequate niacin was fed, the plasma and muscle free trypto phan concentrations of meal-fed rats decreased markedly within 3.5 to 5 hours. Liver concentrations also decreased by 5 hours in the unbalanced group. The concentrations of the amino acids that were added to the diet to cause the imbalance increased con- comitantly with a decrease in plasma tryptophan. These results support the suggestion that in the first situation ( niacin-free diet ) the metabolic response is a result of a deficiency of niacin; whereas, when the tryptophan imbalance is induced in an adequate- niacin diet with 7.8% of an amino acid mixture devoid of tryptophan, the immediate metabolic need is that of tryptophan, the limiting amino acid; a response typical of those observed with other amino acid imbalances. J. Nutr. 104: 1584-1596, 1974.

Regulation of serotonin synthesis

The regulation of serotonin synthesis in the central nervous system seems to involve mechanisms which control the intracellular concentration of tryptophan and the hydroxylation step. Numerous situations are reviewed which demonstrate that changes in the concentration of free tryptophan in plasma and/or in the uptake of the amino acid in brain may alter tryptophan concentration and 5-HT synthesis. In other cases, modifications in 5-HT synthesis were still detected after tryptophan loading, clearly indicating that the tryptophan concentration is not the only critical parameter. In particular, changes in 5-HT synthesis dependent on nerve impulse flow seem to be regulated at the hydroxylation step. In addition, long term regulations of 5-HT synthesis involving changes in tryptophan hydroxylase concentration have been recently demonstrated. How serotoninergic neurons integrate all these regulating factors to modulate 5-HT synthesis is still an open question.

Involvement of the liver in the regulation of tryptophan availability. Possible role in the responses of liver and brain to starvation

The concentrations of free and total (free plus albumin bound) tryptophan were measured in plasma of blood taken from the portal vein, hepatic vein and abdominal aorta of male rats, fed, and starved for one and three days. Liver and brain tryptophan concentrations were measured in similar groups of rats. On starvation, there was an increase in arterial plasma free tryptophan concentration which took place peripherally and was paralleled by an increase in brain tryptophan. In both the fed and starved rats, the portal vein concentrations of free tryptophan were high and as the blood flowed through the liver they were reduced to relatively low levels not directly related to the arterial values. All these changes were due to alterations in degree of binding of tryptophan to plasma albumin. The measurements of plasma total tryptophan concentrations showed that postabsorptively and during starvation there was a net uptake of tryptophan by the peripheral tissues (which included brain), but no overall fall in plasma concentration. At the same time, there was a net release from the liver, and to a lesser extent from the portal-drained tissues. The released tryptophan largely entered the albumin bound plasma pool. Accompanying the hepatic output was a fall in tryptophan concentration in the liver which was apparently caused by altered cell membrane transport. The results suggest (1) that the liver protects the brain from the high free tryptophan level in portal blood, (2) that the availability of tryptophan to the brain is maintained postabsorptively and during starvation by hepatic output into the albumin bound pool and (3) that this release of tryptophan from the liver and the fall in intracellular tryptophan concentration are initiated by altered membrane transport. The pattern of changes is consistent with a role for tryptophan in the mediation of changes in liver protein synthesis and gluconeogenesis and cerebral serotonin turnover on starvation.

Effect of electroconvulsive therapy on plasma unesterified fatty acid and free tryptophan concentrations in man.

Effect of electroconvulsive therapy on plasma unesterified fatty acid and free tryptophan concentrations in man.

Effects on plasma and brain tryptophan in the rat of drugs and hormones that influence the concentration of unesterified fatty acid in the plasma.

1 The effects on tryptophan distribution and metabolism of drugs altering plasma unesterified fatty acid (UFA) concentration were investigated in the rat.2 UFA and plasma free (i.e. ultrafilterable) tryptophan altered in the same direction.3 Catecholamines and L-DOPA increased both plasma UFA and free tryptophan. L-DOPA also increased brain tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) but decreased brain 5-hydroxytryptamine (5-HT).4 Aminophylline increased plasma UFA and free tryptophan and also brain tryptophan, 5-HT and 5-HIAA. Food deprivation had qualitatively similar effects.5 Insulin decreased plasma UFA and free tryptophan in both fed and food-deprived rats. However, while in fed rats these changes were associated with small decreases of brain indoles, in food-deprived animals small increases occurred.6 Nicotinic acid had only small effects in fed rats but it opposed both the UFA and indole changes in food-deprived animals. Total plasma tryptophan increased in nicotinic acid treated, food-deprived rats.7 There was a tendency towards inverse relations between changes of plasma free and total tryptophan.8 The results suggest that drugs which influence plasma UFA through actions on cyclic AMP thereby alter the binding of tryptophan to plasma protein and that this leads to altered distribution and metabolism of tryptophan.

A method for the estimation of free and total acid-soluble plasma tryptophan using an ultrafiltration technique

A simple and reproducible method of extracting free tryptophan in plasma by ultrafiltration is described. Tryptophan concentration in plasma and ultranitrate is measured by a modification of the method of Denckia and Dewey.

Plasma and brain tryptophan changes in experimental acute hepatic failure.

AbstractAn experimental model for acute hepatic failure in man was obtained in pigs by hepatic devascularization. After operation, liver function was grossly impaired, movements became inco‐ordinated and coma ensued. Most animals died 5½–8½ h after operation. Plasma unesteritied fatty acid and free (but not total) tryptophan concentrations rose markedly after operation and correlated significantly with each other. Brain tryptophan concentration increased and correlated significantly with plasma free tryptophan concentration. Increased tryptophan was found in the four brain regions studied (hypothalamus, thalamus, caudate and cortex) and was associated with raised 5‐hydroxytryptamine turnover as indicated by raised 5‐hydroxyindolylacetic acid concentration. Results are discussed in relation to altered tryptophan metabolism in human hepatic coma and to investigations of the influence of plasma unesterified fatty acid and free tryptophan changes on brain tryptophan metabolism in the rat.

TOTAL AND FREE TRYPTOPHAN CONCENTRATION IN THE PLASMA OF DEPRESSIVE PATIENTS

Plasma acid-soluble total and free tryptophan concentrations were measured in twenty-six control women, in a group of twenty-four women with a depressive illness, in eleven patients after recovery, not on drugs, and in eleven recovered patients on prophylactic lithium. The group of depressive women had very significantly reduced plasma levels of free tryptophan, but their levels increased significantly after recovery, although not returning fully to normal. This increase in free tryptophan after recovery was not influenced by the administration of lithium. Total acid-soluble plasma-tryptophan was normal in depressive illness both before and after clinical recovery.

Letter: Dietary carbohydrate increases brain tryptophan and decreases free plasma tryptophan.

THE rate at which the brain synthesizes serotonin varies physiologically as a function of its tryptophan concentration1,2. It has been shown that brain tryptophan, in turn, depends on the relative concentrations in plasma or serum of tryptophan and of the other neutral amino acids which compete with it for uptake into the brain3. Thus, carbohydrate ingestion, which raises plasma tryptophan while depressing the concentrations of its competitors, increases the amount of tryptophan in the brain and accelerates synthesis of serotonin in young rats4; on the other hand, protein consumption causes proportionately greater increases in the other neutral amino acids than in plasma tryptophan, and thus fails to elevate brain tryptophan or serotonin3.

The tyrosine-tryptophan-diagram in a longtime study with depressed patients.

There were determined free plasma tyrosine and tryptophan spectral-photofluorometrically at 22 healthy controls and 81 depressed patients (13 of them were controlled in a long-time-study; mean time: 11 months, and 68 patients were controlled ambulant). The biochemical data were demonstrated in a tyrosine-tryptophan diagram and were correlated with the clinical behaviour of the patients. This correlation only was possible with the postulation of a balance between catecholamine-and indolamine metabolism. Three biochemical parameters are necessary. The values of 1. tyrosine that of 2. tryptophan and not only 3. the resulting quotient. With help of such demonstration we showed this tyrosine-tryptophan balance graphically. We think, that both catecholamine-and the indolamine-hypothesis of depression seem to have their availability.

Serum tryptophan level after carbohydrate ingestion: Selective decline in non-albumin-bound tryptophan coincident with reduction in serum free fatty acids

Plasma free tryptophan exists in two forms, bound to albumin and unbound. Ninety to 180 min after adult males received 75 g glucose, the plasma tryptophan not bound to albumin had decreased maximally by 35%, without significant change in the albumin-bound fraction. The maximal fall in non-bound tryptophan occurred later than the maximal rise in blood glucose and coincided with the fall in non-esterified fatty acids. Addition of oleic acid to serum obtained at this time raised the proportion of free tryptophan to that found in serum from fasting subjects. It is suggested that physiological changes in plasma non-esterified fatty acids levels can affect the availability of free tryptophan to the tissues by altering the binding properties of plasma albumin.

Free tryptophan in plasma and brain tryptophan metabolism.

SYNTHESIS in the brain of the putative transmitter 5-hydroxytryptamine (5HT) is influenced by the concentration of tryptophan; the rate limiting step in 5HT synthesis is the hydroxylation of tryptophan1 by tryptophan hydroxylase, which is normally unsaturated with substrate2. Often when 5HT turnover in the rat brain increases—as indicated by higher concentrations of its metabolite 5-hydroxyindoleacetic acid (5HIAA)—there is a corresponding increase in brain tryptophan. This occurs when the rats are given various drugs known to increase brain 5HT synthesis3, deprived of food4,5, or immobilized5. Therefore the control of brain tryptophan concentration is clearly of some importance.