Plasma Tryptophan Concentration

Plasma tryptophan concentration is a function of dietary tryptophan intake as well as the extent of removal of tryptophan from blood by tissues. The liver is the main organ influencing plasma tryptophan concentration since it actively metabolizes tryptophan while nonhepatic tissues have only relatively limited ability to act in this manner. Following a meal, in the liver, tryptophan stimulates hepatic tryptophan oxygenase activity, which affects tryptophan catabolism and determines how much tryptophan enters the general circulation. 

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Three major factors are considered as important in determining the supply of tryptophan to the brain leading to serotonin synthesis (1) the extent of binding of tryptophan to serum albumin, which influences the pool of free (unbound) tryptophan that interacts with the amino acid carrier mechanism located at the blood-brain barrier, (2) the plasma tryptophan concentrations, and (3) the plasma concentration of other large neutral amino acids (LNAA), which compete with tryptophan for uptake into brain. Each factor can be influenced by the nutritional or hormonal status of the host and also by interorgan relationships in the metabolism of amino acids. 

Jorgensen and Majumdar125 reported that a single tube-feeding of L-tryp-tophan to well-fed adrenalectomized rats stimulated in vivo incorporation of [3H] leucine into brain proteins as well as liver proteins. Also, Nakhla and Majumdar126 reported that tube-feeding tryptophan to well-fed adrenalectomized rats induced an increase in the activity of cerebral acetylcholinesterase, which could be prevented when the animals were pretreated with actinomycin D. Whether or not the enhanced protein synthesis in the brain following tryptophan administration may be related to a rise in brain serotonin level caused by increased plasma tryptophan concentration is not known. 

Cll. Coppen, A., Eccleston, E., Craft, 1., and Bye, P., Total and free plasma-tryptophan concentration and oral contraception. Lancet 2, 1498 (1973). 

In a recent study (Young and Munro, 1971), we have examined the effect of age of the rat on the response of its plasma tryptophan concentration to different levels of dietary tryptophan. The... 

Melatonin (lV-acetyl-5-methoxytryptamine) is a neuro-hormone secreted by the pineal gland from the amino acid precursor [,-tryptophan. Its endogenous secretion is photosensitive and has a circadian rhythm—plasma melatonin concentrations are highest at night in both diurnal and nocturnal animals, and fall with age (1). The nocturnal melatonin peak coincides with a drop in body temperature and increased sleepiness in healthy humans. Oral melatonin has a short half-life (30-50 minutes) and extensive first-pass metabolism. Its clearance is reduced in severe liver disease (2). 

At present, no blood markers are commonly used as indicators of niacin status. Most assessments of niacin nutriture have been based on measurement of the 2 urinary metabolites, N -methylnicotinamide and N -methyl-2-pyridone-5-carboxamide. Normally, adults excrete 20% to 30% of their niacin in the form of methylnicotinamide and 40% to 60% as the pyridone. An excretion ratio of pyridone to methylnicotinamide of 1.3 to 4.0 is thus normal, but latent niacin deficiency is indicated by a value below 1.0. As depletion occurs, the pyridone is absent for weeks before clinical signs are noted, and the methylnicotinamide excretion falls to a minimum at about the time that clinical signs are evident.f HPLC methods are currently the methods of choice, though some capillary electrophoresis methods have been developed. However, the measurement of 2-pyridone and N -methylnicotinamide concentrations in plasma may provide a more reliable metabolite ratio than urine measurements. A newer approach that may prove valuable is the ratio of NAD/NADP in erythrocytes and plasma tryptophan. A ratio of NAD/NADP below 1.0 would be indicative of a risk of developing niacin deficiency. ... 

Schurr et al.43 reported the amino acid concentrations in various tissues of the rat. Using these data to calculate tissue-to-plasma ratios, it becomes apparent that the relative availability of plasma tryptophan to tissues is much less than that of other amino acids. The finding, described elsewhere, that tryptophan in serum or plasma can be present as free and bound (to plasma albumin) is unique among amino acids,44 and this further limits or controls the availability of tryptophan from the blood to organs or tissues, especially the brain. Tryptophan differs from other amino acids in that its concentration in plasma of rats increases (30 to 40%) after fasting, after insulin administration, or after consuming a carbohydrate meal.45... 

This has been reviewed in an earlier section. Normally, the proportion of total plasma tryptophan bound to albumin is 85 to 90%. This equilibrium can be shifted under conditions which raise plasma nonesterified fatty acid (NEFA) concentrations, such as during fasting or stress.198 Since NEFA... 

Wide daily fluctuations in the concentrations of plasma tryptophan, as well as of other amino acids, occur in healthy humans.7 Feigin et al.8 reported a diurnal rhythm for total whole-blood amino acid levels in healthy humans. Daily fluctuations have been observed for all of the nutritionally important amino acids.910 A number of investigators have studied factors that may influence diurnal fluctuations of plasma tryptophan in humans.1112 Many reports cite marked variations, usually decreased levels, of plasma tryptophan, under a variety of disease states. However, it is difficult to assess the importance of these observations. 

The possible relationship between tryptophan and sodium ions has been considered in a number of studies. Herken and Weber165 reported that under certain conditions tryptophan injections intraperitoneally to rats led to a reduction of elimination of Na++. Subsequently, Reuter et al.166 analyzed the alterations of water and electrolyte balances by the use of clearance experiments. The fractional Na++ reabsorption increases, with no increase in the absolute tubular sodium transport rate since the significant reduced plasma-sodium concentration led to a decreased sodium load. The most probable cause of the decreased plasma-sodium concentrations seemed to be retention of sodium-free water under the conditions of infusion. The water retention is compatible with the antidiuretic effect of serotonin. Another relationship between tryptophan and sodium has been reported on the effects of each agent alone or together in vivo or in vitro, on in vitro hepatic nuclear tryptophan receptor binding and hepatic protein synthesis.167 168 This has been considered in detail in Chapter 4. 

After major surgery, the postoperative recovery plasma free tryptophan concentrations were markedly increased over baseline levels, and the plasma free tryptophan to BCAA concentration ratio was also increased after surgery.101 Since plasma albumin concentrations were decreased after surgery, it was considered that this may account for the rise in plasma free tryptophan levels. 

Hoshino, Y., Ohno, Y., Yamamoto, T., Kaneko, M., and Kumashiro, H., Plasma free tryptophan concentration in children with attention deficit disorder, Folia Psychiatr. Neurol. Japonica, 39(4), 531, 1985. 

Plasma concentrations of a number of amino acids are decreased in the second half of the menstrual cycle and when contraceptive steroids are given (A5, C14, R13). Reports that plasma tryptophan levels are normal in OCA-users (A5, Cll, C14) is evidence against the possibility that less tryptophan is available to the brain for 5-hydroxytiyptamine synthesis when women are taking these agents. Plasma tryptophan measurements in depressed women taking contraceptive steroids, however, have not been reported. 

Care must be taken to avoid essential amino acid deficiencies, particularly tryptophan. Tryptophan is difficult to quantify using certain methodologies [14]. Serum albumin binds tryptophan, with one binding site per albumin molecule. Variable albumin binding may make free tryptophan concentrations variable [14]. The frequency of monitoring depends on the patient s age and health status. During early infancy, many clinics measure plasma amino acids along with anthropometries each week (Box 19.5). 

This approach has also been used to study the amino acid requirements of human subjects. Young t 1. (1971) have recently examined the effect of giving increasing levels of dietary tryptophan on the free tryptophan content of plasma and the N balance of young adults (Fig. 2). Their study confirmed the relationship between adequacy of essential amino acid intake and blood levels of the amino acid. At intakes of tryptophan below 3 mg per kg, the plasma levels of tryptophan were low and constant. Between intakes of 3 and 5 mg, tryptophan concentration rose sharply but... 

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