Determination of Free Tryptophan in Plasma and Its Clinical Applications

Hijikata, Yasuyo; Hara, Kuniko; Shiozaki, Yasuko; Murata, Kenjiro; Sameshima, Yoshiko

doi:10.1515/cclm.1984.22.4.291

Cited by 8 publications

(10 citation statements)

References 23 publications

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“…In our previous study (5), no significant difference in plasma free tryptophan concentration was observed between liver cirrhosis patients with or without hepatic encephalopathy, and plasma free tryptophan was significantly higher in liver cirrhosis with bleeding tendency than in without bleeding tendency.…”

Section: Discussionmentioning

confidence: 63%

Changes in Plasma Amino Acids During the Oral Glucose Tolerance Test and the Effect of these Changes on Hepatic Encephalopathy

Hijikata¹,

Shiozaki²,

Sameshima³

1985

Clinical Chemistry and Laboratory Medicine

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Changes in amino acid concentrations in plasma during a 100 g oral glucose tolerance test were investigated in patients with liver cirrhosis and in healthy controls. In the controls, almost all amino acid concentrations reached a nadir about 3 hours after glucose loading, then returned to initial levels after 6 hours. Immunoreactive insulin levels reached a peak about 30 minutes aftef loading, then decreased gradually, reaching initial levels after 6 hours. In the controls, the decrease ratios/defined äs maximum decrease during the 3 hours after loading/initial concentration in plasma, were 0.607 and 0.554 for isoleucine (Ile) and leucine (Leu) respectively and 0.382 for valine (Val) which is significantly lower than for Ile or Leu. A similar tendency was recognized in patients with liver cirrhosis. The initial concentration of tyrosine (Tyr) and phenylalanine (Phe) in liver cirrhosis was significantly higher and their decrease ratios were significantly lower than in controls. Though no difference was observed between initial concentrations of tryptophan (Trp) in controls and liver cirrhosis patients, the decrease ratio of Trp in liver cirrhosis was lower (0.061) than that of controls (0.279) (p < 0.001).The value, t-Trp/BCAA + AAA, i.e. total Trp concentration (mmol/l)/concentration (mmol/1) of branched chain amino acids (BCAA, Ile + Leu + Val) plus aromatic amino acids (AAA, Tyr + Phe), which is known to correlate with the brain Tip concentration of rats (Fernstrom,

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Section: Discussionmentioning

confidence: 63%

Changes in Plasma Amino Acids During the Oral Glucose Tolerance Test and the Effect of these Changes on Hepatic Encephalopathy

Hijikata¹,

Shiozaki²,

Sameshima³

1985

Clinical Chemistry and Laboratory Medicine

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“…39 A similar increase (409%) occurs in patients with liver cirrhosis with oesophageal varices. 40 Because the TDO activity is inhibited in liver diseases, 41 plasma total [Trp] was not decreased in these 2 studies, 39,40 but underwent gradual increases with the severity of the liver dysfunction. 40 42 In another study of patients with renal failure, plasma total [Trp] is decreased by 25% to 40% in those with normal [albumin] and by 60% in those with hypoalbuminemia.…”

Section: Extent Of Elevation Of the [Kyn]/[trp] Ratiomentioning

confidence: 92%

The Plasma [Kynurenine]/[Tryptophan] Ratio and Indoleamine 2,3-Dioxygenase: Time for Appraisal

Badawy

Guillemin

2019

Int J�Tryptophan�Res

163

135

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The plasma kynurenine to tryptophan ([Kyn]/[Trp]) ratio is frequently used to express or reflect the activity of the extrahepatic Trp-degrading enzyme indoleamine 2,3-dioxygenase (IDO). This ratio is increasingly used instead of measurement of IDO activity, which is often low or undetectable in immune and other cells under basal conditions, but is greatly enhanced after immune activation. The use of this ratio is valid in in vitro studies, eg, in cell cultures or isolated organs, but its ‘blanket’ use in in vivo situations is not, because of modulating factors, such as supply of nutrients; the presence of multiple cell types; complex structural and functional tissue arrangements; the extracellular matrix; and hormonal, cytokine, and paracrine interactions. Determinants other than IDO may therefore be involved in vivo. These are hepatic tryptophan 2,3-dioxygenase (TDO) activity and the flux of plasma-free Trp down the Kyn pathway. In addition, conditions leading to accumulation of Kyn, eg, inhibition of activities of Kyn monooxygenase and kynureninase, could lead to elevation of the aforementioned ratio. In this review, the origin of use of this ratio will be discussed, variations in extent of its elevation will be described, evidence against its indiscriminate use will be presented, and examining determinants other than IDO activity and their correlates will be proposed for future studies.

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“…Unlike other amino acids, Trp exists in both bound and free forms in blood (22). (23). There is evidence that it is the free Trp that is transported across the blood-brain bamer as substrate for 5-HT synthesis (17).…”

Section: Discussionmentioning

confidence: 99%

Effect of Sodium Benzoate and Sodium Phenylacetate on Brain Serotonin Turnover in the Ornithine Transcarbamylase-Deficient Sparse-Fur Mouse

et al. 1988

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Herein we examine the effects of sodium benzoate and sodium phenylacetate on feeding and central serotonin turnover in a child with citrullinemia and in an animal model of congenital hyperammonemia, the ornithine transcarbamylase-deficient sparse-fur (spfly) mouse. In the child, when the benzoate/phenylacetate dosage was increased from 200 to 375 mg/kg/day each, feeding decreased. There was an accumulation of benzoate and phenylacetate in blood and cerebrospinal fluid a s well a s an increased concentration of 5-hydroxyindoleacetic acid, a neurochemical marker for serotonin turnover, in cerebrospinal fluid. In the mouse, sodium benzoate had a biphasic effect on both plasma ammonium levels and brain serotonin turnover. Two percent oral benzoate was associated with an increase in ammonium level, while a 3% dose led to a decrease in ammonium. There was a similar effect on serotonin turnover noted in both the hyperammonemic spfly and control CD-lly mice. Sodium phenylacetate did not have a consistent effect on serotonin turnover. The mechanism by which benzoate increases brain serotonin turnover appears to involve competition with tryptophan for albumin binding sites. This results in increased free tryptophan in serum and brain. W e speculate that some of the clinical symptoms of benzoate intoxication may be a consequence of altered serotonin turnover in the brain. We suggest that drug levels be monitored during therapy. 36excretion in children with inborn errors of urea synthesis (1). This has resulted in prolonged survival. However, both intravenous drugs used to treat acute hyperammonemia and inadvertent oral overdoses have been associated with clinical toxicity including anorexia, irritability, lethargy, and coma (1, 2). Symptoms of intoxication in part simulate those of hyperammonemia. The mechanism of these behavioral alterations is unclear. Bachmann et al. (3) re~orted increased brain uvtake of Tm. the precursor of serotbnin,tn rats injected with 1 mmol/kg of sddium benzoate. Increased brain uvtake of T m and increased brain serotonin turnover have also been reported in experimentally induced and naturally occurring hyperammonemia (4-7). These findings, together with data showing an association of anorexia with increased serotonin turnover in children with urea cycle disorders (8), suggest that benzoate intoxication may involve altered serotonin turnover.In studying the effect of benzoate and phenylacetate on serotonin turnover, we initially present a case report of a child with citrullinemia who developed toxic symptoms during high dose therapy and was found to have increased levels of the metabolite of serotonin, HIAA, in cerebrospinal fluid. We then examine in more detail the interaction of hyperammonemia and benzoate/ phenylacetate treatment on brain serotonin turnover in the chronically hyperammonemic ornithine transcarbamylase deficient sparse-fur (spf/y) mouse. METHODSBiochemical methods. Plasma ammonium was measured by a microfluorometric adaptation of a glutamate dehydrogenase method as previously d...

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Determination of Free Tryptophan in Plasma and Its Clinical Applications

Cited by 8 publications

References 23 publications

Changes in Plasma Amino Acids During the Oral Glucose Tolerance Test and the Effect of these Changes on Hepatic Encephalopathy

Changes in Plasma Amino Acids During the Oral Glucose Tolerance Test and the Effect of these Changes on Hepatic Encephalopathy

The Plasma [Kynurenine]/[Tryptophan] Ratio and Indoleamine 2,3-Dioxygenase: Time for Appraisal

Effect of Sodium Benzoate and Sodium Phenylacetate on Brain Serotonin Turnover in the Ornithine Transcarbamylase-Deficient Sparse-Fur Mouse

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