Plasma Tryptophan In Patients Research Articles

Elevated Plasma Tryptophan in Patients with Anorexia Nervosa Compared with Hypotrophic Controls.

We hypothesized that anorexia nervosa (AN) is associated with pathological amino acid metabolism. This study aimed to identify amino acids exhibiting abnormal metabolism in patients with AN compared with those in low-nutrient controls. This was a single-center, retrospective, observational study that compared patients with AN with a low-nutrient control group. All participants were admitted to the Kitasato University Hospital Emergency Center between January 1, 2018, and January 31, 2021. Both the AN and low-nutrient control groups had five patients each. Plasma amino acid category testing was conducted at the same institution for both groups. Patient sex, age, height, weight, and comorbidities were retrospectively extracted. Plasma amino acid fractions, total amino acids, total essential amino acids, total nonessential amino acids, branched-chain amino acids (sum of valine, isoleucine, and leucine), and amino acid concentrations and ratios were compared between the two groups. Data were analyzed using the Mann-Whitney U test. Body mass index was lower in the AN group (p = 0.00794). Tryptophan levels were significantly higher in the AN group (p = 0.00794). Other amino acid values, the sum of amino acid values, and amino acid ratios were not significantly different between both groups. Serum tryptophan levels were higher in the AN group than in the low-nutrient group, and AN may be associated with abnormal amino acid metabolism.

KYNURENINE METABOLITES AND INFLAMMATION MARKERS IN DEPRESSED PATIENTS TREATED WITH FLUOXETINE OR COUNSELLING

1. Depression could result from changes in tryptophan availability caused by activation of the kynurenine pathway as a result of inflammation. In the present study, we examined patients newly diagnosed with depression to determine whether kynurenines and related factors change in parallel with improvements in mood. 2. Concentrations of 5-hydroxytryptamine (5-HT; serotonin), 5-hydroxyindoleacetic acid (5-HIAA), oxidized tryptophan metabolites, brain-derived neurotrophic factor (BDNF) and inflammatory mediators (interleukin (IL)-2, C-reactive protein (CRP), neopterin) were measured in peripheral blood during an 18 week period of treatment with fluoxetine, fluoxetine plus tri-iodothyronine (T(3)) or psychiatric counselling. 3. The results showed significant improvements in mood, with reduced 5-HT concentrations in patients given fluoxetine and a rise in plasma tryptophan in patients given counselling or fluoxetine and T(3). The addition of T(3) to the fluoxetine regimen appeared to slow recovery from depression, although the use of T(3) was associated with a fall in thyroxine concentrations. Changes in 5-HT concentrations did not correlate with psychiatric scores and were seen only in drug-treated groups, not those given counselling. There were no associated changes in absolute concentrations of kynurenines, BDNF, CRP, neopterin or IL-2. With fluoxetine treatment, there were correlations between the concentrations of kynurenine metabolites and the psychiatric rating scores, whereas no correlations were found with BDNF or inflammatory markers. 4. It is concluded that depression scores are largely independent of inflammatory status, but kynurenine metabolism may be related to the degree of depression after fluoxetine treatment.

4-pyridone-3-carboxamide ribonucleoside triphosphate accumulating in erythrocytes in end stage renal failure originates from tryptophan metabolism

We recently identified an erythrocyte nucleotide accumulating in end-stage renal disease as 4-pyridone-3-carboxamide ribonucleotide triphosphate (4PYTP), a nucleotide never described previously. Plasma tryptophan concentration has been previously reported to be reduced in patients in chronic renal failure that is in turn associated with elevated precursors of tryptophan metabolism, including L -kynurenine and quinolinic acid, both of which have been implicated in the neurotoxic manifestations of chronic renal failure. Here we compare mean erythrocyte 4PYTP, and plasma tryptophan concentrations, in controls and four patient groups with renal impairment (10 per group) and confirmed a reduction in plasma tryptophan in patients on dialysis that corrected with renal transplantation. We found: An inverse correlation between plasma tryptophan and red cell 4PYTP concentrations (R(2)=0.44, P<0.001) when all patients were grouped together. Restoration of both tryptophan and 4PYTP concentrations to control values was only achieved following renal transplantation. 4PYTP was absent from erythrocytes in Molybdenum cofactor (MoCF) deficiency implicating aldehyde oxidase/dehydrogenase, a Molybdenum requiring enzyme. High 4PYTP erythrocyte concentrations in adenine or hypoxanthine-phosphoribosyltransferase deficient patients in severe uremia (113 microM and 103 microM), confirmed the lack of involvement of either enzyme in 4PYTP formation. We propose that 4PYTP is formed by a novel route involving the oxidation of the intermediates of NAD turnover from quinolinic acid by aldehyde oxidase.

Plasma tryptophan during weight restoration in patients with anorexia nervosa

Anorexia nervosa (AN) is a mental disorder characterized by low weight and concerns about body shape and weight. Disturbance in serotonin function has been described as central to the psychobiology of this disorder. Plasma tryptophan (TRP), the essential amino acid needed for serotonin production, is known to be low following acute caloric restriction but has not been measured during the course of refeeding. Plasma TRP and other large neutral amino acids (LNAA) levels were measured in 26 female patients with AN and 15 control subjects. Patient levels were measured at admission for inpatient treatment, after 1 week of treatment, and upon weight restoration to weight > or =90% ideal body weight (IBW). For 17 patients, an additional assessment was made when weight reached 80% IBW. Plasma levels were obtained on one occasion from healthy control subjects. Plasma TRP and TRP/LNAA ratio increased significantly during refeeding process. Plasma TRP in patients was 46.88 nmol/mL (SD = 19.59) on admission and 55.54 nmol/L/mL (SD = 8.1) at normal weight, p < .05. The ratio of TRP to LNAA was .11 (SD = .03) on admission and .13 (SD = .02) at normal weight, p < .05. Plasma TRP is significantly lower in low-weight patients than in healthy control subjects (TRP = 53.73 [SD = 8.21]), but there was no significant difference between control subjects and normal-weight patients. Plasma TRP normalizes during the course of refeeding, supporting the hypothesis that serotonin function is disturbed in patients with anorexia nervosa.

The inflammatory response system and the availability of plasma tryptophan in patients with primary sleep disorders and major depression

Background: It is now well established that major depression is accompanied by an immune-inflammatory system response and that indicators of the latter are inversely correlated with lower availability of plasma tryptophan in depression. Inflammation and infection can alter sleep architecture, whereas sleep disturbances can impair immune functions. Aims and Methods: The aims of the present study were to examine: (i) immune-inflammatory markers, i.e. serum interleukin-6 (IL-6), IL-8, IL-6 receptor (IL-6R), IL-1R antagonist (IL-1RA), gp130, and prostaglandin E2 (PGE2) production by mitogen-stimulated whole blood and the availability of plasma tryptophan in patients with primary sleep disorders, major depression and healthy volunteers; and (ii) the relationships between the availability of tryptophan and indicators of the immune-inflammatory response system. Results: Mitogen-stimulated release of PGE2, and serum IL-6 and IL-8, were significantly increased in both depressed and sleep disordered patients compared to normal controls. Serum IL-1RA was significantly higher in depressed patients than in normal controls. Patients with depression and sleep disorders had a significantly lower availability of tryptophan than normal controls. There were significant and inverse relationships between the availability of plasma tryptophan and serum IL-1RA, IL-6 and IL-8. Conclusions: The results suggest that (i) there is an activation of the immune-inflammatory response system in primary sleep disorders and depression; and (ii) the decreased availability of plasma tryptophan may be related to the inflammatory system response.

Roles of hippurate and indoxyl sulfate in the impaired ligand binding by azotemic plasma.

Despite extensive efforts by many investigators the chemical basis of most uremic disorders is not known. We have been studying a circumscribed disorder, impaired plasma protein binding of acidic drugs and endogenous metabolites, hoping to discover investigative approaches which might be applicable to study of more complex uremic disorders. Our initial interest in the problem arose from our finding of markedly reduced levels of plasma tryptophan in patients with renal failure, before and after long-term dialysis treatment. This change appeared to be due to impaired binding of tryptophan by azotemic plasma (1). The initial hypothesis proposed by others that binding is impaired because plasma albumin is per se abnormal has little support. Substantial evidence indicates that retained uremic solutes, which bind to plasma proteins, account for this defect (2). Two aromatic anions, hippurate and indoxyl sulfate, accumulate to substantial levels in uremia and are known to be moderate to strong displacers of several albumin-bound model probes in vitro (3-5). In addition, Lichtenwalner et al have implied that o-hydroxyhippurate may be an important binding inhibitor in azotemic plasma (6). To evaluate the relative importance of these three aromatic anions as binding inhibitors, we have developed highly sensitive and specific HPLC methods to measure their concentrations in plasma of patients With a wide range of renal failure. We have also determined the binding of 14 C-salicylate by normal plasma, azotemic plasma and normal plasma “spiked” with a wide range of hippurate and indoxyl sulfate and correlated the concentrations of these ligands with salicylate binding. Salicylate was used as a probe because it binds to both of the major binding sites on albumin for aromatic anions. Finally, we have determined the effect of wide variations in concentrations of pH, calcium and chloride on binding.