Plasma tryptophan

Another important function of albumin is its ability to bind various ligands. These include free fatty acids (FFA), calcium, certain steroid hormones, bilirubin, and some of the plasma tryptophan. In addition, albumin appears to play an important role in transport of copper in the human body (see below). A vatiety of drugs, including sulfonamides, penicilhn G, dicumarol, and aspirin, are bound to albumin this finding has important pharmacologic implications. 

Lin, R. C., Ngai, S. H., and Costa, E. (1969) Lysergic acid diethylamide Role in conversion of plasma tryptophan to brain serotonin (5-hydroxytryptamine). Science. 166 237-239. 

Anderson, I.M., Parry-Billings, M., Newsholme, E.A., et al. (1990) Dieting reduces plasma tryptophan and alters brain 5-HT function in women. Psychol Med 20 785-791. 

Aylward M Estrogens, plasma tryptophan levels in peiimenopausal patients, in The Management of the Menopause and Post-Menopausal Years. Edited by Campbell S. Baltimore, MD, University Park Press, 1976, pp 135-147... 

Delgado PL, Charney DS, Price LH, et al Serotonin function and the mechanism of antidepressant action reversal of antidepressant-induced remission by rapid depletion of plasma tryptophan. Arch Gen Psychiatry 47 411-418, 1990b Delgado PL, Price LH, Miller HL, et al Rapid serotonin depletion as a provocative challenge test for patients with major depression relevance to antidepressant action and the neurobiology of depression. Psychopharmacol Bull 27 321-330, 1991... 

Delgado PL, Charney DS, Price LH, et al. Serotonin function and the mechanism of antidepressant action reversal of antidepressant induced remission by rapid depletion of plasma tryptophan. Arch Gen Psychiatry 1990 47 411-418. 

Weber LW, Lebofsky M, Stahl BU, et al. 1992b. Comparative toxicity of four chlorinated dibenzo-p-dioxins (CDDs) and their mixture. Part III Structure-activity relationship with increased plasma tryptophan levels, but no relationship to hepatic ethoxyresorufin o-deethylase activity. Arch Toxicol 66(7) 484-488. 

Fu CS, Swendseid ME, Jacob RA, and McKee RW (1989) Biochemical markers for assessment of niacin nutritional status in young men levels of erythrocyte niacin coenzymes and plasma tryptophan./owraa/o/JVMtrifton 119,1945-9. 

The production of IL-2 and IFN-y is the typical marker of a type-1 immune response. In conhary to schizophrenia, IFN-y is produced in greater amounts by lymphocytes of patients withMD than of healthy conhols (Seidel etal., 1996a). Higher plasma levels of IFN-y in depressed patients, accompanied by lov er plasma tryptophan availability were described (Maes et al., 1994). Data on IL-2 in major depression are mainly reshicted to the estimation of its soluble receptor sIL-2R in the peripheral blood. Increased sIL-2R levels reflect an increased production of IL-2. The blood levels of sIL-2R were repeatedly found to be increased in MD patients (Sluzewska et al., 1996 Maes et al., 1995a, b). 

Song C, Lin A, Bonaccorso S, Heide C, Verkerk R, Kenis G, Bosmans E, Scharpe S, Whelan A, Cosyns P, De Jongh R, Maes M (1998) The inflammatory response system and the availability of plasma tryptophan in patients with primary sleep disorders and major depression. J Affect Disord 49 211-219. 

In keeping with the presumed importance of serotonin in the pathophysiology of BN is the finding that a reduction in the synthesis of serotonin in the brain, brought about by a diet deficient in tryptophan, precipitates a loss of eating control and an increased concern with body image in recovered BN patients (Smith et al. 1999). Chronic depletion of plasma tryptophan may be one of the mechanisms by which dieting leads to the development of BN in vulnerable subjects. 

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. ... 

Investigators 30 found no distinct relationship between either total plasma tryptophan or tyrosine and depression. However, they30 did report that free plasma tryptophan in depressed patients was always higher than controls and returned to normal upon good clinical improvement. In contrast, other investigators found lower plasma tryptophan levels in... 

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... 

Fernstrom, J. D. and Wurtman, R. J., Brain serotonin content Physiological dependence on plasma tryptophan levels, Science, 173,149,1971. 

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. 

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... 

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. 

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. 

IFN-y), which activates and leads to expression of IDO and decreased plasma tryptophan levels, may develop evidence of depression, dementia, as well as fatigue and weakness, findings not uncommon in conditions having enhanced immune system activity, such as AIDS, infection, autoimmune diseases, and related conditions. 

Free plasma tryptophan increased significantly after 40 to 60 min of exercise (bicycle), but total tryptophan did not reveal a significant change.49 Prolactin levels correlated with free plasma tryptophan throughout the tests. The induced increase in free plasma tryptophan was probably mediated by... 

Moja et al.57 treated rats with cycloheximide, an inhibitor of protein synthesis, and then fed a tryptophan-free mixture. The cycloheximide treatment largely prevented the marked decrease of plasma tryptophan (total and free). These data supported the hypothesis that protein synthesis was the mechanism through which the ingested tryptophan-free mixture decreased blood tryptophan levels. However, this interpretation was not consistent with the findings of Wunner et al.58 and Sidransky et al.,59 who observed a low rate of polyribosome formation and low incorporation of labeled amino acids in the livers of rodents previously fasted and then acutely fed a tryptophan-free amino acid mixture. 

It is of interest that Moja et al.60 reported that healthy humans receiving a tryptophan-free amino acid mixture revealed a decrease of plasma tryptophan levels. 

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