Hostname: page-component-586b7cd67f-dsjbd Total loading time: 0 Render date: 2024-11-24T03:23:33.673Z Has data issue: false hasContentIssue false

Tryptophan metabolism and vitamin B6 nutritional status in patients with schistosomiasis mansoni and in infected mice

Published online by Cambridge University Press:  06 April 2009

E. N. M. Njagi
Affiliation:
Department of Biochemistry and Molecular Biology, University College and Middlesex School of Medicine, University College London, Gower Street, LondonWC1E 6BT
D. A. Bender
Affiliation:
Department of Biochemistry and Molecular Biology, University College and Middlesex School of Medicine, University College London, Gower Street, LondonWC1E 6BT
G. B. A. Okelo
Affiliation:
Department of Medicine, Kenyatta National Hospital, University of Nairobi, Nairobi, Kenya

Extract

Patients infected with Schistosoma mansoni showed an abnormal response to a test dose of tryptophan, with little increase in the urinary excretion of kynurenine, hydroxykynurenine, xanthurenic and kynurenic acids, N1-methyl nicotinamide, methyl pyridone carboxamide, 5-hydroxytryptamine or 5-hydroxyindoleacetic acid. In contrast to previous reports, this is different from the pattern of tryptophan metabolism seen in vitamin B6 deficiency. Furthermore, the patients' plasma concentrations of pyridoxal phosphate were within the reference range, and supplementation for 5 days with 20 mg vitamin B6/day did not affect tryptophan metabolism. Treatment with a single dose of Praziquantel resulted in a substantial restoration of normal tryptophan metabolism. In mice infected with S. mansoni there was a similar impairment of tryptophan metabolism, as shown by considerably reduced formation of 14CO2 after the administration of a tracer dose of [14C]tryptophan. Again, the administration of vitamin B6 supplements did not correct tryptophan metabolism in the mice. Treatment with Praziquantel resulted in substantial restoration of the production of 14CO2 from [14C]tryptophan. There was no evidence of vitamin B6 deficiency (as determined by erythrocyte aspartate aminotransferase activation coefficient) associated with infection in the mice, although there was a redistribution of pyridoxal phosphate between tissues, with a reduction in the concentration of liver, spleen and kidney, and an increase in skeletal muscle.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1992

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abdel-Daim, M. H., Konbar, A. A., Kelada, F. S. & Moustafa, M. H. (1971). Studies on the functional capacity of the tryptophan-niacin pathway in bilharzial children from rural areas. Transactions of the Royal Society of Tropical Medicine and Hygiene 65, 668–71.CrossRefGoogle Scholar
Abdel-Tawab, G. A., Kelada, F. S., Kelada, N. L., ABDEL-Daim, M. H. & Makhgrun, N. (1966). Studies on the aetiology of bilharzial cancer of the urinary bladder: (v) excretion of tryptophan metabolites in urine. International Journal of Cancer 1, 377–82.CrossRefGoogle Scholar
Abdel-Tawab, G. A., Ibrahim, E. K., EL-Masri, A., Alghorab, M. & Makhyoun, N. (1968). Studies on tryptophan metabolism in bilharzial bladder cancer patients. Investigative Urology 5, 591601.Google ScholarPubMed
Abdel-Tawab, G. A., Kholieff, T. S., EL-Sewedy, S. M., Abbassy, A. S., Zeitoun, M. M. & Hassanein, E. A. (1969). Studies on tryptophan metabolism in bilharzial hepatic fibrosis and non-bilharzial hepatic cirrhosis in childhood. Acta Paediatrica Scandinavica 58, 54–8.CrossRefGoogle ScholarPubMed
Abdul-Fadl, M. A. M. & Khalafallah, A. S. (1961). Studies on the urinary excretion of certain tryptophan metabolites in bilharziasis and its possible relations to bladder cancer in Egypt. British Journal of Cancer 15, 489–92.Google Scholar
Adams, E. (1979). Fluorimetric determination of pyridoxal phosphate in enzymes. Methods in Enzymology 62, 407–10.CrossRefGoogle Scholar
Andrews, P. (1981). Preclinical data of Praziquantel: a summary of the efficacy of Praziquantel against schistosomes in animal experiments and notes on its mode of action. Arztneimittel-Forschung 31, 538–41.Google Scholar
Belongia, E. A., Hedberg, C. W., Gleich, G. L., White, K. E., Mayeno, A. N., Loegering, D. A., Dannette, S. L., Pirie, P. I., Macdonald, K. L. & Osterholm, M. T. (1990). An investigation of the cause of the eosinophilia–myalgia syndrome associated with tryptophan use. New England Journal of Medicine 323, 357–65.Google Scholar
Bender, D. A. (1980). Inhibition in vitro of the enzymes of the oxidative pathway of tryptophan metabolism and nicotinamide nucleotide synthesis by Benserazide, Carbidopa and isoniazid. Biochemical Pharmacology 29, 707–12.CrossRefGoogle ScholarPubMed
Bender, D. A. (1983). Effects of oestradiol and vitamin B6 on tryptophan metabolism in the rat: implications for the interpretation of the tryptophan load test for vitamin B6 nutritional status. British Journal of Nutrition 50, 3342.CrossRefGoogle ScholarPubMed
Bender, D. A. (1987). Oestrogens and vitamin B6 – actions and interactions. World Review of Nutrition and Dietetics 51, 140–88.CrossRefGoogle Scholar
Bender, D. A. (1989). Vitamin B6 requirements and recommendations. European Journal of Clinical Nutrition 43, 289309.Google Scholar
Bender, D. A., Gartey-Sam, K. & Singh, A. (1989). Effects of vitamin B6 deficiency and repletion on the uptake of steroid hormones into uterus slices and isolated liver cells of rats. British Journal of Nutrition 61, 619–28.CrossRefGoogle ScholarPubMed
Bender, D. A., Njagi, E. N. M. & Danielian, P. S. (1990). Tryptophan metabolism in vitamin B6-deficient mice. British Journal of Nutrition 63, 2736.CrossRefGoogle ScholarPubMed
Bender, D. A., Tagoe, C. E. & Vale, J. A. (1982). Effects of oestrogen administration on vitamin B6 and tryptophan metabolism in the rat. British Journal of Nutrition 47, 609–14.CrossRefGoogle ScholarPubMed
Bender, D. A. & Totoe, L. (1984). High doses of vitamin B6 in the rat are associated with inhibition of hepatic tryptophan metabolism and increased uptake of tryptophan into the brain. Journal of Neurochemistry 43, 733–6.CrossRefGoogle ScholarPubMed
Bennett, J. L. & Bueding, E. (1973). Uptake of 5-hydroxytryptamine by Schistosoma mansoni. Molecular Pharmacology 9, 311–19.Google ScholarPubMed
Biehl, J. P. & Vilter, R. W. (1954). Effect of isoniazid on vitamin B6 metabolism: its possible significance in producing isoniazid neuritis. Proceedings of the Society for Experimental Biology and Medicine 85, 389–92.CrossRefGoogle ScholarPubMed
Carpenter, K. J. & Kodicek, E. (1950). The fluorimetric estimation of N 1-methylnicotinamide and its differentiation from coenzyme 1. The Biochemical Journal 46, 421–6.CrossRefGoogle Scholar
Denckla, W. D. & Dewey, H. K. (1967). The determination of tryptophan in plasma, liver and urine. Journal of Laboratory and Clinical Medicine 69, 160–9.Google ScholarPubMed
Department of Health (1991). Dietary Reference Values for Food Energy and Nutrients for the United Kingdom, London: HMSO.Google Scholar
Gordon, A. E. & Meldrum, B. S. (1970). Effect of insulin on brain 5HT and 5HIAA. Biochemical Pharmacology 19, 3042–4.CrossRefGoogle Scholar
Holman, W. I. M. (1954). A colorimetric method for the determination of the principal metabolites of nicotinic acid in human urine. The Biochemical Journal 56, 512–20.CrossRefGoogle ScholarPubMed
Joseph, M. H. & Risby, D. (1975). The determination of kynurenine in plasma. Clinica Chimica Acta 63, 197204.Google Scholar
Khalafallah, A. S. & Abdul-Fadl, M. A. M. (1964). Studies of the urinary excretion of certain tryptophan metabolites before and after tryptophan loading dose in bilharziasis, bilharzial bladder cancer and certain other types of malignancies in Egypt. British Journal of Cancer 18, 592604.Google Scholar
Mousa, A. H., Abdel-Wahab, A. F., Mousa, W., Abdel-Tawab, G. A., Saad, A. A. & Kelada, N. L. (1967). Tryptophan metabolism in hepatosplenic bilharziasis. Transactions of the Royal Society of Tropical Medicine and Hygiene 61, 640–7.CrossRefGoogle ScholarPubMed
Njagi, E. N. M. & Bender, D. A. (1990). Schistosoma mansoni: Effects on tryptophan metabolism in mice. Experimental Parasitology 70, 4354.CrossRefGoogle ScholarPubMed
Satoh, K. & Price, J. M. (1958). Fluorimetric determination of kynurenic acid and xanthurenic acid in human urine. Journal of Biological Chemistry 230, 781–9.CrossRefGoogle Scholar
Schimke, R. T., Sweeney, E. W. & Berlin, C. M. (1965). The roles of synthesis and degradation in the control of rat liver tryptophan pyrrolase. Journal of Biological Chemistry 240, 322–31.CrossRefGoogle ScholarPubMed
Schuster, L., Bates, A. & Hirsch, C. A. (1978). A sensitive radiochemical assay for serum glutamic-oxaloacetic transaminase. Analytical Biochemistry 86, 648–54.Google Scholar
Smithers, S. R. & Terry, R. J. (1965). The infection of laboratory hosts with cercariae of Schistosoma mansoni and the recovery of adult worms. Parasitology 55, 695700.CrossRefGoogle ScholarPubMed
Statutory Instruments, (1990). Number 1728. The tryptophan in food regulations. London, H.M.S.O.Google Scholar
Watanabe, M., Watanabe, Y. & Okada, M. (1970). A new fluorimetric method for the determination of 3-hydroxykynurenine. Clinica Chimica Acta 27, 461–6.CrossRefGoogle ScholarPubMed