Tryptophan oral loading

Furthermore, Knapp and Gassmann (Gla, K3, K8) loaded normal subjects and patients having various cutaneous disorders with 10 g dl-tryptophan orally, and determined the 24-hour excretion of xanthurenic acid. Values indicating an abnormal excretion of xanthurenic acid were observed in 22 of 55 patients, predominantly those with cutaneous allergic or light sensitivity manifestations. In many instances these abnormal results were normalized following therapy with vitamin Bs. 

Diagnostic tests (a) Measure plasma concentration of Bg (b) Measure urinary excretion of xanthurenate (yellow product) following an oral load of tryptophan. Normally tryptophan catabolism proceeds via the Bg-dependent kynureninase but In Bg deficiency, xanthurenate accumulates... 

Oral loading with tryptophan in Hartnup disorder will lead to increased production of indole compounds which can be analysed in the urine. 

A test that can be used for the diagnosis of pyridoxine deficiency. It consists of giving an oral load of tryptophan and measur-... 

Excess xanthurenate in the urine. Xanthure-nate levels in the urine increase with vitamin B6 deficiency because B (as pyridoxal phosphate) is necessary for the further chemical transformation of 3-hydroxykynurenine. Pyridoxine deficiency may be detected by giving the patient a loading dose of tryptophan. If pyridoxine deficiency is present, there will be a detectable excess of xanthurinate in the urine. Oral contraceptives may increase urinary xanthurenate levels, possibly... 

One of the rare studies of the excretion of tryptophan metabolites, both spontaneous and after load, by patients with hematological disorders, is the work of Altman and Miller (A4). They reported an elevated urinary excretion of anthranilic acid in 9 children with an unusual congenital anemia referred to as erythrogenesis imperfecta (A4). Oral administration of 1.6 g L-tryptophan to one patient led to increased urinary excretion of anthranilic acid as well as other intermediary metabolites of tryptophan. Massive doses of riboflavin per os during 30 days caused no change in the hematological status, but there appeared to be a decrease in the amount of anthranilic acid excreted. 

The disappearance of xanthurenic acid after pyridoxine dierapy suggested the possibility of a latent Be deficiency (Dl). Dahler-Vollen-weider (D2) screened 159 children in respect to the urinary picture of tryptophan metabolites and found an abnormal excretion of xanthurenic acid in 17, whereas 142 fell within normal limits after tryptophan loading. There seems to be an increased rate of excretion widi age. In the newborn the excretion was the lowest while the maximal values were found in the age group 10-16 years. During periods of rapid growth there was a high excretion rate of xanthurenic acid, which was not appreciably affected by daily oral administration of 100 mg pyridoxine. 

In human diabetes Rosen et al. (R5) found that 20 diabetic patients with and without retinopathy excreted on the average significantly greater quantities of xanthurenic acid after an oral test load of 10 g DL-tryptophan than did nondiabetic controls. No significant difference was found in the xanthurenic acid output of diabetic patients with and without retinopathy (R5). 

The disease is a rare inherited disorder characterized by a progressive degeneration of the lenticular nucleus in the brain and by cirrhosis of the liver. Barbeau et al. (Bl) studied a case of Wilson s disease which presented normal ceruloplasmin and serum copper values but increased excretion of kynurenine, 3-hydroxykynurenine, and conjugated anthra-nilic acid in xurine after an oral dose of 2 g L-tryptophan. This defect in tryptophan metabolism could be related to that of other amino acids and to the actual content of ceruloplasmin in Wilson s disease (Bl). These findings corroborated Marver s (M2) investigations demonstrating a definite excretion of kynurenine and 3-hydroxykynurenine in abnormal proportions after a tryptophan load in a case of Wilson s disease. 

At One time it was thought that women taking oral contraceptives were at risk for B deficiency. This notion seem-S to have been in error. The error was due to a misinterpretation of the tryptophan load lest. As mentioned earlier, a deficiency in vitamin B(,can induce the accumulation of specific intermediates of the tryptophan catabolic pathway and enhanced excretion in the urine. Oral contraceptives can also induce ar increase in the formation and excretion of specific intermediates by stimulating the activity of specific enzymes of the tryptophan catabolic pathway, This stimulation was responsible for the false indications of deficiency. Independently of the tryptophan load test, there continues to be some evidence for risk associated with the use of oral contraceptives. Oral contraceptive use may result in lowered levels of plasma vitamin Bf, Tlicsc lowered levels may result in a vitamin deficiency when coupled with pregnancy and lactation. 

Walsh et al.132 first described that urinary excretion of tryptophan metabolites of the hepatic kynurenine-nicotinic acid pathway was decreased after oral tryptophan loading of chronic alcoholic subjects within 1 day of cessation of ethanol intake. This suggests inhibition of hepatic TP activity in his subjects. Friedman et al.133 subsequently showed that serum kynurenine levels after oral tryptophan loading were high in alcoholics after 1 month of abstinence. This finding of inhibition of liver TP activity should result in increased availability of circulating tryptophan to the brain for serotonin synthesis. However, further experimentation is still needed to establish fully the above interpretation. 

All of the studies that suggested that oral contraceptives cause vitamin deficiency used the tryptophan load test (section 11.9.5.1). When other biochemical markers of status were also assessed, they were not affected by oral contraceptive use. Furthermore, most of these studies were performed using the now obsolete high-dose contraceptive pills. 

This is the excretion product of 3-hydroxykynurenic acid, an intermediate in the conversion of tryptophan to nicotinic acid. Pyridoxal phosphate is required as a cofactor for the enzyme, kynureninase, which catalyses the conversion of 3-hydroxykynurenic acid to 3-hydroxyanthrinilic acid. In patients with pyridoxine deficiency, 3-hydroxykynurenic acid accumulates and is excreted in the urine as xanthurenic acid. Xanthurenic acid can therefore be measured in urine (especially after giving an oral typtophan load) in order to detect pyridoxine deficiency. 

The failure of CSF 5HIAA to increase when tryptophan is given to depressed subjects could be due to enhanced diversion of tryptophan via the pyrrolase pathway, as depressives given an oral tryptophan load excrete larger amounts of its metabolites formed through liver tryptophan pyrrolase action than do a control group [327]. This is reasonable as pyrrolase is induced by adrenocorticoids [328] and there is much evidence of elevated adrenocortical secretion in depressive illness [329, 330, 331] especially in the early morning [332-335]. Defective feedback inhibition of ACTH release may be responsible [336, 337]. Whether raised adrenocorticoid secretion is a primary or secondary manifestation of the illness is debatable [338, 339] and raised adrenocorticoid levels without depression (and vice versa) are commonplace. 

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