The Relationship Between Biopterin and Folate Metabolism

  • J. P. Harpey

Abstract

Phenylketonuria (PKU) is a metabolic disorder that is inherited in an autosomal recessive pattern and is caused by a defect in the hepatic phenylalanine (PA) hydroxylating system. This system consists of two enzymes, phenylalanine 4-hydroxylase (PAH) (EC 1.14.16.1) and dihydropteridine reductase (DHPR) (EC 1.6.99.7), and a coenzyme, tetrahydrobiopterin (BH4), which acts not only on PAH but also on tyrosine 3-hydroxylase (EC 1.14.16.2) and tryptophan 5-hydroxylase (EC 1.14.16.4) — the former on the dopamine and norepinephrine synthesis pathway, the latter on the serotonin synthesis pathway (Fig. 1). During each hydroxylation cycle of these three enzymes, BH4 is oxidized to quininoid dihydrobiopterin (q-BH2), the latter being transformed partly into L-erythro-7, 8-dihydrobiopterin (7,8-BH2). They are reduced to BH4 by DHPR and by dihydrofolate reductase (DHFR) (EC 1.5.1.3), respectively (Fig. 1).

Keywords

Dopamine Folate Tryptophan Phenylalanine Cobalamin 

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References

  1. 1.
    Smith I (1974) Atypical phenylketonuria accompanied by a severe progressive neurological illness unresponsive to dietary treatment. Arch Dis Child 49:242Google Scholar
  2. 2.
    Harpey J-P (1983) Les défauts de synthèse des bioptérines: les déficits complets (réductase et synthétase). Arch Fr Pédiatr 40:231–235PubMedGoogle Scholar
  3. 3.
    Smith I, Hyland K, Kendall B. Leeming RJ (1985) Clinical role of pteridine therapy in tetrahydrobiopterin deficiency. J Inherited Metab Dis 8 (Suppl 1): 39–45PubMedCrossRefGoogle Scholar
  4. 4.
    Harpey J-P, Rey F, Leeming RJ (1984) Seven year follow-up in a child with early-treated dihydropteridine-reductase deficiency. 22nd Annual symposium, Society for the Study of Inborn Errors of Metabolism. Newcastle upon Tyne, 1984Google Scholar
  5. 5.
    Irons M, Levy HL, O’Flynn ME, Stack CV, Langlais PJ, Butler IJ, Milstien S, Kaufman S (1987) Folinic acid therapy in treatment of dihydropteridine reductase deficiency. J Pediatr 110:61–67PubMedCrossRefGoogle Scholar
  6. 6.
    Pollock RJ, Kaufman S (1978) Dihydropteridine reductase may function in tetrahydrofolate metabolism. J Neurochem 31:115–123PubMedCrossRefGoogle Scholar
  7. 7.
    Turner AJ, Ponzio F, Algeri S (1974) Dihydropteridine reductase in rat brain: regional distribution and the effect of eatecholamine-depleting drugs. Brain Res 70:550–558Google Scholar
  8. 8.
    Nichol CA, Lee CL, Edelstein MP, Chao JY, Duch DS (1983) Biosynthesis of tetrahydrobiopterin by de novo and salvage pathways in adrenal medulla extracts, mamalian cell cultures and rat brain in vivo. Proc Natl Acad Sci USA 80:1546–1550PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Matthews RG, Kaufman S (1980) Characterization of the dihydropteridine reductase activity of the pig liver methylenetetrahydrofolate reductase. J Biol Chem 255:6014–6017PubMedGoogle Scholar
  10. 10.
    Howells D, Smith I, Leonard J, Hyland K (1986) Tetrahydrobiopterin in dihydropteridine reductase deficiency. N Engl J Med 314:520–521PubMedGoogle Scholar
  11. 11.
    Harpey J-P, Le Moel G, Zittoun J (1983) Follow-up in a child with 5,10-methylenetetrahy- drofolate reductase deficiency. J Pediatr 103(6): 1007PubMedCrossRefGoogle Scholar
  12. 12.
    Clayton PT, Smith I, Harding B, Hyland K, Leonard K, Leeming RJ (1986) Subacute combined degeneration of the cord, dementia and parkinsonism due to an inborn error of folate metabolism. J Neurol Neurosurg Psychiatry 49:920–927PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Leeming RJ, Harpey J-P, Brown SM, Blair JA (1983) Tetrahydrofolate and hydroxocobalamin in the management of dihydropteridine reductase deficiency. J Ment Deflc Res 26:21–25Google Scholar

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© Springer-Verlag Berlin Heidelberg 1989

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  • J. P. Harpey

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