Tryptophan and metabolites

Mefford, I. N., and Barchas, J. D., 1980, Determination of tryptophan and metabolites in rat brain and pineal tissue by reversed-phase high-performance liquid chromatography with electrochemical detection,/. Chromatogr. 181 187-193. 

Higher-Order Derivative Spectrophotometry of Tryptophan and Metabolites , in Progress in TTyptophan and Serotonin Research, edited by H. G. Schlossberger, W. Kochen, B. Linzen, H. Steinhart, 140-142. Berlin, New York Walter de Gruyter u. Co., 1984. 

The analysis of amino acids involves chromatographic issues similar to those encountered in analysis of simple amines. Underivatized amino acids have, with a few exceptions, weak UV absorbance and a strong tendency to interact with stationary phases in undesirable ways. Underivatized amino acids are normally separated with ion exchange chromatography, then visualized post-column by reaction with ninhydrin, o-phthaladehyde (OPA), or other agents. Underivatized tryptophan and the metabolites kynurenine, 3-hydroxykynurenine, kynurenic acid, and 3-hydroxyanthranilic acid, were separated on a Partisphere 5-p ODS column with fluorescent detection.121... 

Herve, C., Beyne, P., Jamault, H., and Delacoux, E., Determination of tryptophan and its kynurenine pathway metabolites in human serum by high-performance liquid chromatography with simultaneous ultraviolet and fluo-rimetric detection, ]. Chromatogr. B, 675, 157, 1996. 

Patients sustain convulsions and neurological deterioration. The urine contains low levels of the metabolites of serotonin, norepinephrine and dopamine. The reductase also plays a role in the maintenance of tetrahydrofolate levels in brain, and some patients have had low folate levels in the serum and CNS. Treatment has been attempted with tryptophan and carbidopa to improve serotonin homeostasis and with folinic acid to replete diminished stores of reduced folic acid. This therapy is sometimes effective. Diagnosis involves assay of DHPR in skin fibroblasts or amniotic cells. Phenylalanine hydroxylase activity is normal. 

The affect of Li+ on the metabolism of serotonin (5-hydroxytryp-tamine, 5-HT) is equivocal. A number of studies consistently find a Li+-induced increase in the levels of the major metabolite, 5-hydroxyin-doleacetic acid (5-HIAA), in rat brain and in human CSF [155], which appears to reflect an increase in the rate of synthesis of 5-HT [156]. Li+-induced increases in the level of the amino acid precursor, tryptophan, and in the uptake of tryptophan by brain have also been reported [157], implying elevated tryptophan availability during Li+ treatment. In rat brain, chronic Li+ decreases the activity of tryptophan hydroxylase, the enzyme which, when activated by a Ca2+ and calmodulin-dependent protein kinase, leads to the synthesis of 5-HT [158]. Ca2+ increases the strength of binding of tryptophan to the enzyme, whereas Li+ has the opposite effect [159]. Tryptophan uptake is coupled to 5-HT utilization by a negative feedback mechanism and, therefore, the Li+-induced inhibition of tryptophan hydroxylase with a resultant decrease in 5-HT utilization could produce the observed increase in tryptophan uptake. 

Alkaloids from tryptophan. The alkaloid harmine, which is found in several families of plants, can be formed from tryptophan and acetaldehyde (or pyruvate) in the same manner as is indicated for the formation of papaverine in Fig. 25-10. Some other characteristic plant metabolites such as psilocybine, an hallucinogenic material from the mushroom... 

INDOLES. Indole is a heteroaromatic compound consisting of a fused benzene and pyrrole ring, specitieally benzo[fc pyrrole. The indole ring is incorporated into the structure of Ihe amino acid tryptophan and occurs in proteins and in a wide variety of plant and animal metabolites. 

Molecules with structures as diverse as carbamoyl-phosphate, tryptophan, and cytidine triphosphate are feedback inhibitors of the E. coli glutamine synthase. The feedback inhibition is cumulative, with each metabolite exerting a partial inhibition on the enzyme. Why would complete inhibition of the glutamine synthase by a single metabolite be metaboli-cally unsound ... 

Echinulin.—Detailed work40 has been carried out in the biosynthesis of echinulin (115). This fungal metabolite arises from tryptophan and alanine through the... 

Metabolites of the ergoline type [as (128)], as well as those of type (119), have been isolated from Penicillium roqueforti. The incorporation has been observed of radioactive samples of tryptophan and mevalonate into both series of metabolites, and of histidine into those of type (119).44 Diversion from tryptophan into the two independent biosynthetic pathways is initiated on the one hand by the formation of (122) and on the other by reaction with histidine to give a diketopiperazine precursor for metabolites such as (119). Which route is followed is temperature-dependent. 

Urine Progressive form of albuminuria from the nonprogressive form of albuminuria Type 1 diabetic patients normoalbuminuric56. After 5.5 years micro/macroalbuminuric 26 normoalbuminuric 26 GC-MS LC-MS Acylcarnitines, acyl-glycines, and metabolites related to the tryptophan metabolism (56)... 

The structures of the penitrems were elucidated156 mainly by extensive n.m.r. studies, both on the natural material and on 13C-enriched material isolated after administration of appropriate 13C-labelled precursors (tryptophan and acetate) to the cultures. Structure (16a) incorporates the proposed relative stereochemistry of penitrem A, but no deductions concerning the stereochemistry of the other metabolites were made. Penitrem A is a powerful toxin, and causes sustained tremors, disco-ordination, and convulsions in laboratory and farm animals. 

The remaining two chapters provide fascinating insights into the alkaloids of mammals and of amphibians. As a follow-up to a chapter published in Volume 21 of this series, Arnold Brossi offers a critical review of the current status of the knowledge of mammalian alkaloids, such as those derived from tryptophan and from phenylalanine, and in particular he reviews the literature regarding the fascinating subject of whether morphine-like alkaloids are indeed mammalian metabolites. 

Kynurenine Hydroxylase Kynurenine hydroxylase is an FAD-dependent mixed-function oxidase of the outer mitochondrial membrane, which uses NADPH as the reductant. The activity of kynurenine hydroxylase in the liver of riboflavin-deficient rats is only 30% to 50% of that in control animals, and deficient rats excrete abnormally large amounts of kynurenic and anthranilic acids after the administration of a loading dose of tryptophan, and, correspondingly lower amounts of quinolinate and niacin metabolites. Riboflavin deficiency may thus be a contributory factor in the etiology of pellagra when intakes of tryptophan and niacin are marginal (Section 8.5.1). 

Despite our understanding of the biochemistry of niacin, we still cannot account for the characteristic photosensitive dermatitis in terms of the known metabolic lesions. There is no apparent relationship between reduced availability of tryptophan and niacin, and sensitivity of the skin to ultraviolet (UV) light. The only biochemical abnormalities that have been reported in the skin of pellagrins involve increased catabolism of the amino acid histidine leading to a reduction in the concentration of urocanic acid, a histidine metabolite that is the major UV-absorbing compound in normal dermis (see Figure 10.6). 

Tryptophan and Zinc Absorption Boses of 4 mg Zn and 2 mg Cu were given in Trutol to subjects consuming a diet in which tryptophan was the limiting amino acid Absorption of Zn and Cu was also measured when they received the same diet plus a picolinic acid supplement Ficolinic acid is a metabolite of tryptophan which is thought to enhance zinc absorption (17) Picolonic acid was not present in the isotope dose The diets contained 0 8-l 2 mg Cu/day and 2 7-3 6 mg Zn/day (by analysis) Total tryptophan content of the diet was approximately 250 mg/day (calculated) Ficolinic acid supplementation was at a level of 10 mg/day ... 

As previously stated, quantitative methods agree that all human beings normally excrete a few mg daily of the so-called oncogenic metabolites derived from tryptophan, and increased levels of urinary metabolites are not specific for bladder tumors. Also, normal and increased excretion of tryptophan metabolites is found in individuals of both sexes, whereas bladder tumors are rarer among females. 

G6. Gershoff, S. N., and Prien, E. L., Excretion of urinary metabolites in calcium oxalate urolithiasis. The effect of tryptophan and vitamin Bg administration. Am. ]. Clin. Nutr. 8, 812-816 (1960). 

As with the other B vitamins that act as coenzymes biochemical assessment of vitamin Bg can, be made by direct chemical analysis of the vitamer or its metabolites, or by functional means. Measurements that have been used are PLP in plasma or red cells, its metabolite 4 PA in urine or plasma, the activity and activation coefficient of the red cell aminotransferases (aspartate and alanine), and the tryptophan load metabolite excretion test. As no single marker adequately reflects status, a combination of these markers olfers the best approach. 

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