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Tetrahydrobiopterin metabolism, neurological disease and mental retardation

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Scientific Studies in Mental Retardation

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Abstract

Tetrahydrobiopterin (THB) is widely distributed in human body fluids and tissues in concentrations from 2 μg/ml to 1 ng/ml being found in urine, plasma, cerebrospinal fluid, breast milk, liver, kidney, brain, gut, breast, erythrocytes, carcinoid tumours, colonic and rectal tumours and breast tumours. It is the coenzyme in the conversion of phenylalanine to tyrosine, tyrosine to dopa and tryptophan to 5-hydroxytryptophan. It therefore has a key role in the formation of the CNS neurotransmitters, dopamine, noradrenaline and serotonin (Leeming et al., 1981).

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References

  • Aziz, A., Blair, J.A., Leeming, R.J., and Sylvester, P.E. (1982a). Tetrahydrobiopterin metabolism in Down’s syndrome and in non-Down’s syndrome mental retardation. J. Ment. Defic. Res. 26, 67–71

    Google Scholar 

  • Aziz, A.Z., Blair, J.A., Leeming, R.J. and Sylvester, P.E. (1982b). unpublished

    Google Scholar 

  • Aziz, A., Leeming, R.J. and Blair, J.A. (1983). Tetrahydrobiopterin metabolism in senile dementia of Alzheimer type (SDAT). J. Neurology, Neurosurgery and Psychiatry, 46, 410–413

    Google Scholar 

  • Barford, P.A., Blair, J.A. and Leeming, R.J. (1983). Dihydropteridine activity in normal and diseased man. Second Winter Symposium on the Chemistry and Biology of Pterins. (in press)

    Google Scholar 

  • Blair, J.A., Hilburn, M.E. and Leeming, R.J. (1982a). unpublished

    Google Scholar 

  • Blair, J.A., Hilburn, M.E., Leeming, R.J., McIntosh, M.J. and Moore, M.R. (1982b). Lead and tetrahydrobiopterin metabolism: possible effects on IQ. Lancet, i, 964

    Google Scholar 

  • Blair, J.A., Leeminq, R.J. and Parsons, A. (1982c). unpublished

    Google Scholar 

  • Blair, J.A., Leeming, R.J., Primrose, D.A. and Sylvester, P.E. (1982d). unpublished

    Google Scholar 

  • Blair, J.A., Whitburn, S.B., Pheasant, A.E., Leeming, R.J., Morar, C. and Al-Beir, A. (1983). Proc. Seventh Int. Symp. Chem. Pteridines. W. de Gruyter, Berlin and New York. 165–169

    Google Scholar 

  • Curtius, H.-Ch., Muldner, H. and Niederweiser, A. (1982). Tetrehydrobiopterin: efficacy in endogenous depression and Parkinson’s disease. J. Neural Transmission, 55, 301–318

    Article  Google Scholar 

  • Danks, D.M., Bartholome, K., Clayton, B.E., Curtius, H., Grobe, H., Kaufman, S., Leeming, R.J., Pfleiderer, W., Rembold, H. and Rey, F. (1978). Malignant hyperphenylalaninaemia. Current status (June 1977). J. Inher. Metab. Dis. 1, 49–53

    Google Scholar 

  • Davison, A.M., Oil, H., Walker, G.S. and Levins, A.M. (1982). Water supply aluminium concentration, dialysis dementia and effect of reverse osmosis water treatment. Lancet, iii, 785–787

    Google Scholar 

  • Dhondt, J.L., Ardouin, P., Hayte, J.M. and Farriaux, J.P. (1981). Developmental aspects of pteridine metabolism and relationships with phenylalanine metabolism. Clin. Chim. Acta 110, 143–152

    Google Scholar 

  • Dhondt, J.L., Bellahsene, Z., Vanhille, Ph. and Noel, C. (1982). Tetrahydrobiopterin metabolism in chronic uraemia: possible explanation of dialysis encephalopathy. Lancet, iii 491

    Google Scholar 

  • d’Orban, P. T. and Dalton, J. (1980). Violent crime and the menstrual cycle. Psychol. Med. 10, 353–359

    Google Scholar 

  • Eggar, C., Barford, P.A., Blair, J.A., Pheasant, A.E. and Oates, D.G. (1983). Dihydropteridine reductase levels in human normal and neoplastic tissues. Proc. Seventh. Int. Symp. Chem. Biol. Pteridines, 869–874

    Google Scholar 

  • Hilburn, M.E. (1979). Environmental lead in perspective. Chem. Soc. Rev., 8, 63–64

    Google Scholar 

  • Leeming, R.J. (1979). Metabolism of biopterin and its derivatives in man and the rat. Ph.D. Thesis, Chemistry Department, University of Aston in Birmingham

    Google Scholar 

  • Leeming, R.J. (1982). personal communication

    Google Scholar 

  • Leeming, R.J. and Blair, J.A. (1979). Dialysis dementia, aluminium and tetrahydrobiopterin metabolism. Lancet 1, 556

    Article  CAS  PubMed  Google Scholar 

  • Leeming, R.J. and Blair, J.A. (1980a). The effects of pathological and normal physiological processes on biopterin derivative levels in man. Clin. Chim. Acta 108, 103–111

    Google Scholar 

  • Leeming, R.J. and Blair, J.A. (1980b). Serum Crithidia levels in disease, Biochem. Med., 23, 122–125

    Google Scholar 

  • Leeming, R.J., Blair, J.A., Aziz, A. and Brown, S.E. (1982). unpublished

    Google Scholar 

  • Leeming, R.J., Blair, J.A., Green, A. and Raine, D.N. (1976a). Biopterin derivatives in normal and phenylketonuric patients after oral loads of L-phenylalanine, L-tyrosine and L-tryptophan. Arch. Dis. Childhood 51, 771–777

    Google Scholar 

  • Leeming, R.J., Blair, J.A. and Melikian, V. (1979). Biopterin derivatives in senile dementia. Lancet i, 215

    Google Scholar 

  • Leeming, R.J., Blair, J.A., Melikian, V. and O’Gorman, D.J. (1976b). Biopterin derivatives in human body fluids and tissues. J. Clin. Path. 29, 444–451

    Google Scholar 

  • Leeming, R.J., Pheasant, A.E. and Blair, J.A. (1981). The role of tetrahydrobiopterin in neurological disease: a review. J. Ment. Defic. Res., 25, 231–241

    Google Scholar 

  • LeWitt, R.A., Newman, R.P., Miller, L.P., Lovenberg, W. and Eldridge, R. (1983). Treatment of dystonia with tetrahydrobiopterin. New Engl. J. Med., 308, 157–158

    Google Scholar 

  • Lovenberg, W., Levine, R.A., Robinson, D.S., Ebert, M., Williams, A.C. and Calne, D.B. (1979). Hydroxylase cofactor activity in cerebrospinal fluid of normal subjects and subjects with Parkinson’s disease. Science, 204, 624–627

    Article  CAS  PubMed  Google Scholar 

  • McDermott, J.R., Smith, A.I., Ward, M.K., Parkinson, I.S. and Ken, D.N.S. (1978). Brain aluminium concentration in dialysis encephalopathy. Lancet i, 901–903

    Google Scholar 

  • McIntosh, M., Moore, M.E., Blair, J.A., Hilburn, M.E., and Leeming, R.J. (1982). Lead and tetrahydrobiopterin metabolism in man and animals. Clin. Sci. Mol. Med. 44P

    Google Scholar 

  • Morar, C., Whitburn, S.B., Blair, J.A., Leeming, R.J. and Wilcock, G.K. (1983). Tetrahydrobiopterin metabolism in senile dementia of the Alzheimer type. J. Neurol. Neurosurg. Psychiat. 46, 582

    Google Scholar 

  • MRC/DHSS (1982). Phenylketonuria news letter no. 8.

    Google Scholar 

  • Niederweiser, A., Curtius, H-Ch., Wang, M. and Leupold, D. (1982). Atypical phenylketonuria with defective biopterin metabolism. Monotherapy with tetrahydrobiopterin. Eur. J. Pediatrics, 138, 110–112

    Google Scholar 

  • Purdy, S.E. and Blair, J.A. (1980). Rat liver dihydropteridine reductase inhibition. Biochem. Soc. Trans. 8, 565

    Google Scholar 

  • Purdy, S.E., Blair, J.A. and Barford, P.A. (1981a). Inhibition of dihydropteridine reductase by dopamine. Biochem. J. 195, 769–771

    Google Scholar 

  • Purdy, S.E., Blair, J.A., Leeming, R.J. and Hilburn, M.E. (1981b). Effect of lead on tetrahydrobiopterin synthesis and salvage: A cause of neurological dysfunction. Int. J. Environmental Studies 17, 141–145

    Google Scholar 

  • Rey, F., Harpey, J.P., Leeming, R.J., Blair, J.A., Aicardi, J. and Rey, J. (1977). Les hyperphenylalaninemies avec activite normale de la phenylalanine-hydroxylase: Le deficit en tetrahydrobiopterine et la deficit en dihydropteridine reductase. Arch. Franc. Ped. 34, CIX-CXX

    Google Scholar 

  • Rey, J., Saudubray, J.M., Leeming, R.J., Niederweiser, A., Curtius, H-Ch., and Rey, J. (1983). Les deficits partiels en tetrahydrobiopterin. Arch. Franc. Ped., 40, 237–241

    Google Scholar 

  • Ruttle, M. (1982). Proc. CLEAR Int. Symp. on Lead. London. in press

    Google Scholar 

  • Williams, A., Eldrige, R., Levine, R., Lovenberg, W. and Paulson, G. (1979). Low CSF hydroxylase co-factor (tetrahydro-biopterin) levels in inherited dystonia. Lancet ii, 410

    Google Scholar 

  • Young, J.H., Kelly, B. and Clayton, B.E. (1982). Reduced levels of biopterin and dihydropteridine reductase in Alzheimer type dementia. J. Clin. Exp. Gerontol. in press

    Google Scholar 

  • Brooksbank, B.W.L. and Balazs, R. (1983). Superoxide dismutase and lipoperoxidation with Down’s syndrome foetal brain. Lancet, (in press)

    Google Scholar 

  • Fridovich, I. (1979). Superoxide dismutases: defence against endogenous superoxide radical. In: Oxygen Free Radicals and Tissue Damage; CIBA Found.Symp. No. 65, pp 77–93

    Google Scholar 

  • McCay, P.B. and King, M.M. (1980). Vitamin E: its role as a biological free radical scavenger and its relationship to the microsomal mixed function oxidase system. In: Vitamin E: a Comprehensive Treatise, Dekker, New York, pp 289–317

    Google Scholar 

  • Scott, B.S., Petit, T.L., Becker, L.E. and Edwards, B.A.V. (1982). Abnormal electric membrane properties of Down’s syndrome dorsal root ganglion neurons in cell culture. Dev. Brain. Res. 2, 257–270

    Google Scholar 

  • Sinet, P.M., Michelson, A.M., Bagin, A., Lejeune, J.K. and Jerome, H. (1975). Increase in glutathione peroxidase activity in erythrocytes from trisomy 21 subjects. Biochem. Biophys. Res. Commun. 67, 910–915

    Google Scholar 

  • Brewster T.G., Moskowitz M.A., Kaufman S., Breslow J.L., Milstien S. and Abroms I.F. (1979). Dihydropteridine reductase deficiency associated with severe neurologic disease and mild hyperphenylalaninemia. Pediatrics, 63, 94–99

    CAS  PubMed  Google Scholar 

  • Butler I.J., Koslow S.H., Krumholz A., Holtznan N.A. and Kaufman S. (1978). A disorder of biogenic amines in dihydropteridine reductase deficiency. Ann. Neurol., 3, 224–230

    Google Scholar 

  • Davison A.N. (1977). The biochenistry of brain development and mental retardation. The Eleventh Blake Marsh Lecture, delivered to the Roy. Coll. Psycn., February

    Google Scholar 

  • Hsia Y.E. and Wolf B. (1981). Disorders of amino acid metabolism. In: Basic Neurochemistry (3rd ed.), (Siegel G.J., Albers R.W., Agranoff B.W. and Katzman R., eds.). Little, Brown a Co., Boston, 563–600

    Google Scholar 

  • Javoy-Agid F., Ploska A. and Agid Y. (1981). Microtopography of tyrosine hydroxylase, glutamic acid decarboxylase, and choline acetyltransferase in the substantia nigra and ventral tegmental area of control and Parkinsonian brains. J. Neurochem.. 37. 1218–1227

    Article  CAS  PubMed  Google Scholar 

  • Kettler R., Bartholini G. and Pletscher A. (1974). In vivo enhancement of tyrosine hydroxylation in rat striatum by tetrahydrobiopterin. Nature (London), 249, 476–478

    Article  CAS  Google Scholar 

  • Leeming R.J., Blair J.A., Melikian V. and O’Gorman D.J. (1976). Biopterin derivatives in human body fluids and tissues. J. Clin. Path., 29, 444–451

    Google Scholar 

  • Mandell A.J. and Russo P.V. (1981). Short-term regulation of hydroxylase cofactor activity in rat brain. J. Neurochem., 37, 1573–1578

    Article  CAS  PubMed  Google Scholar 

  • Ordonez L.A. (1977). Control of the availability of the brain of folic acid, vitamin B12, and choline. In: Nutrition and the Brain, 1, (Wurtman R.J. and Wurtman J.J., eds.), New York, Raven Press, 205–248

    Google Scholar 

  • Williams A.C., Levine R.A., Chase T.N., Lovenberg W. and Calne D.B. (1980). CSF hydroxylase cofactor levels in some neurological diseases. J. Neurol. Neurosurg. Psych., 43, 735–738

    Google Scholar 

  • Adolfsson R., Gottfries C.G., Roos B.E. and Winblad B. (1979). Changes in brain catecholamines in patients with dementia of Alzheimer type. J. Psychiatry, 135, 216–23

    Article  CAS  Google Scholar 

  • Benton J.S., Bowen D.M., A11en S.J., Haan E.A., Davison A.N., Neary D., Murphy R.P. and Smurden J.S. (1982). Alzheimer’s Disease as a disorder of isodendritic core. Lancet, I

    Google Scholar 

  • Bondareff W., Mountjoy C.Q. and Roth M. (1981). Selective loss of neurons of origin of projection to cerebral cortex (nucleus locus coeruleus). Senile dementia. Lancet, 1, 783–84

    Google Scholar 

  • Bowen D.M., Smith C.B., White P. and Davison A.N. (1976). Neuro-transmitter related enzymes and indices of hypoxia in senile dementia and other abiotrophies. Brain, 99, 459–96

    Article  CAS  PubMed  Google Scholar 

  • Burnstock G. (1975). Purinergic transmission. In: Iversen L.L., Iversen S.D and Snyder S.H. Eds. Handbook of Psychopharmacology, 5, New York, Plenum Press, 131–94

    Google Scholar 

  • Cross A.J., Crow T.J., Perry E.K., Perry R.H., Blessed G. and Tomlinson B.E. (1981). Reduced dopamine beta hydroxylase activity in Alzheimer’s Disease. Brit. Med. J., 282, 93–94

    Google Scholar 

  • Davies P. and Maloney A.J. (1976). Selective loss of central loss of central cholinergic neurons in Alzheimer’s Disease. Lancet, II, 1403

    Google Scholar 

  • Deutsch J.A. (1971). The cholinergic synapse and the site of memory. Science, 174, 788–94

    Article  CAS  PubMed  Google Scholar 

  • Drachman D.A. (1977). Memory and cognitive function in man: does the cholinergic system have a specific role? Neurology, 27, 783–90

    Article  CAS  PubMed  Google Scholar 

  • Fredholm B.B. and Hedqvist P. (1980). The modulation in neuron transmission by purine nucleotides and nucleosides. Biochem. Pharmacol., 29, 1635–43

    Article  CAS  PubMed  Google Scholar 

  • Lloyd K.G., Hornykiewicz 0., Davidson L., Shannak K., Farley I., Goldstein M., Shibuya M., Kelly W.N. and Fox I.H. (1981). Biochemical evidence of dysfunction of brain neuro-transmitters in the Lesch-Nyhan syndrome. New Engl. J. Med., 305, 1106–11

    Google Scholar 

  • Mesulam M-M and Van Hoesen T.W. (1976). Acetylcholinesterase-rich projections from the basal forebrain of the rhesus monkey to neocortex. Brain Res., 109, 152–57

    Article  CAS  PubMed  Google Scholar 

  • Perry E.K., Perry R.H., Blessed G. and Tomlinson B.E. (1977). Necropsy evidence of central cholinergic deficits in senile dementia. Lancet, 1, 189

    Article  CAS  PubMed  Google Scholar 

  • Phillis J.W. (1979). Diazepam potentiation of purinergic depression of central neurons. Can. J. Physiol. Pharmacol., 57, 432–5

    Article  CAS  PubMed  Google Scholar 

  • Pull I. and Mcllwain H. (1977). Adenine mononucleotides and their metabolites liberated from and applied to isolated tissues of the mammalian brain. Neuro. Chem. Res., 2, 203–16

    CAS  Google Scholar 

  • Rodbell M. (1980). The role of hormone receptors and GTP - regulatory proteins in membrane transduction. Nature, 284, 17–22

    Article  CAS  PubMed  Google Scholar 

  • Skolnick P., Paul S.M. and Marangos P.J. (1980). Purines as endogenous ligands of the benzodiazepine receptor. Fed. Proc., 39, 305–5

    Google Scholar 

  • Whitehouse P.J., Price D.L., Struble R.G., Clark A.W., Colye J.T. and De Long M.R. (1982). Alzheimer’s Disease in senile dementia: loss of neurons in the basal forebrain. Science, 215, 1237–39

    Article  CAS  PubMed  Google Scholar 

  • Winblad B., Adolfsson R., Carlsson A. and Gottfries C-G. (1982). Biogenic amines in brains of patients with Alzheimer’s Disease. In: Corkin S., Davies K.L., Crowdon J.H., Usdin E. and Wurtman R.J. Eds. Alzheimer’s Disease: a Report of Progress and Research (Ageing volume XIX). Raven Press, New York, 25–33

    Google Scholar 

  • Yates C.M., Ritchie I.M., Simpson J., Maloney A.F.J. and Gordon A.(1981). Noradrenaline in Alzheimer-type dementia in Down’s syndrome. Lancet, II, 39–40

    Google Scholar 

  • Sinet P.M., Couturier J., Dutrillaux B., Poissonnier M., Raoul 0., Rethore M.O., Allard D., Lejeune J. and Jerome H. (1976). Exp. Cell Res., 97, 47–55

    Article  CAS  PubMed  Google Scholar 

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Authors
  1. J. A. Blair
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  2. R. J. Leeming
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Editor information

Editors and Affiliations

  1. The Department of Child Health, University of Manchester, UK

    John Dobbing

  2. The Department of Psychology, The University, Hull, UK

    A. D. B. Clarke

  3. The Bethlem Royal Hospital, UK

    J. A. Corbett

  4. The Hester Adrian Research Centre, University of Manchester, UK

    J. Hogg

  5. The Newcomen Centre, Guy’s Hospital, London, UK

    R. O. Robinson

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© 1984 The Royal Society of Medicine

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Blair, J.A., Leeming, R.J. (1984). Tetrahydrobiopterin metabolism, neurological disease and mental retardation. In: Dobbing, J., Clarke, A.D.B., Corbett, J.A., Hogg, J., Robinson, R.O. (eds) Scientific Studies in Mental Retardation. Palgrave Macmillan, London. https://doi.org/10.1007/978-1-349-06870-8_8

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  • DOI: https://doi.org/10.1007/978-1-349-06870-8_8

  • Publisher Name: Palgrave Macmillan, London

  • Print ISBN: 978-1-349-06872-2

  • Online ISBN: 978-1-349-06870-8

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