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Molecular Cloning and Recombinant Expression of the Human Liver Phenylalanine Hydroxylase Stimulating Factor Revealed Structural and Functional Identity to the Dimerization Cofactor for the Nuclear Transcription Factor HNF-1α

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Chemistry and Biology of Pteridines and Folates

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 338))

Abstract

Conversion of phenylalanine to tyrosine by the cytosolic liver enzyme phenylalanine hydroxylase (PAH) requires phenylalanine, molecular O2 and the obligatory cofactor tetrahydrobiopterin (BH4)1.The phenylalanine hydroxylation produces stoichiometrically an oxidized BH4 intermediate, the pterin-4α-carbinolamine (4α-CA). This unstable intermediate is proposed to be dehydrated to the quinonoid dihydrobiopterin (q-BH2) by the phenylalanine hydroxylase stimulating factor (PHS; also termed pterin-4α-carbinolamine dehydratase)2. The presence of the dihydropteridine reductase (DHPR) together with NADH completes the reductive recycling of the BH4 cofactor. A deficiency in PAH, PHS or DHPR leads to different forms of hyperphenylalaninemia3.

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References

  1. C.R. Scriver, S. Kaufman and S.L.C. Woo, The hyperphenylalaninemias, in: “The Metabolic Basis of Inherited Disease,” C.R. Scriver, A.L. Beaudet, W.S. Sly and D. Valle, eds., McGraw-Hill, New York (1989).

    Google Scholar 

  2. R.A. Lazarus, S.J. Benkovic and S. Kaufman, J. Biol. Chem. 258:10960 (1983).

    CAS  Google Scholar 

  3. F.K. Trefz, U. Lichter-Konecki and D. Konecki, Current Opinion in Pediatrics. 1:421 (1989).

    Article  Google Scholar 

  4. N. Blau, H.-Ch. Curtius, T. Kuster, A. Matasovic, G.Schoedon, L. Dhondt, P. Guibaud, T. Giudici and M.Blaskovics, J. Inher. Metab. Dis. 2:335 (1989).

    Article  Google Scholar 

  5. N. Blau, L. Kierat, H.-Ch. Curtius, M. Blaskovics and T. Giudici, J. Inker. Metab. Dis. 15:409 (1992).

    Article  CAS  Google Scholar 

  6. D.B. Mendel, P.A. Kahavari, P.B. Conley, M.K. Graves, L.P. Hansen, A. Admon and G. Crabtree,Science. 254:1762 (1991).

    Article  PubMed  CAS  Google Scholar 

  7. C.R. Hauer, I. Rebrin, B. Thöny, F. Neuheiser, H.-Ch. Curtius, P. Hunziker, N. Blau, S. Ghisla and C.W.Heizmann, J. Biol Chem. 268:4828 (1993).

    PubMed  CAS  Google Scholar 

  8. B.A. Citron, M.D.Davis, S. Milstien, J. Gutierrez, D.B. Mendel, G.R. Crabtree and S. Kaufman, Proc. Natl. Acad. Sci. USA . 89:11891 (1992).

    Article  PubMed  CAS  Google Scholar 

  9. J. Sambrook, E.F. Fritsch and T. Maniatis. “Molecular Cloning: A Laboratory Manual,” Cold Spring Harbor, New York (1989)

    Google Scholar 

  10. C.Y. Huang, E.E. Max and S. Kaufman, J. Biol. Chem. 248:4235 (1973).

    PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Division of Clinical Chemistry, University Children’s Hospital, CH-8032, Zurich, Switzerland

    Beat Thöny, Frank Neuheiser, Charles R. Hauer & Claus W. Heizmann

Authors
  1. Beat Thöny
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  2. Frank Neuheiser
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  3. Charles R. Hauer
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  4. Claus W. Heizmann
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Editor information

Editors and Affiliations

  1. Dept of Pharmacology College of Medicine, Universily of South Alabama, Mobile, AL, 36688, USA

    June E. Ayling

  2. Dept. of Biochemistry College of Medicine, University of South Alabama, Mobile, AL, 36688, USA

    M. Gopal Nair

  3. College of Medicine, Universily of South Alabama, Mobile, AL, 36688, USA

    Charles M. Baugh

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© 1993 Springer Science+Business Media New York

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Thöny, B., Neuheiser, F., Hauer, C.R., Heizmann, C.W. (1993). Molecular Cloning and Recombinant Expression of the Human Liver Phenylalanine Hydroxylase Stimulating Factor Revealed Structural and Functional Identity to the Dimerization Cofactor for the Nuclear Transcription Factor HNF-1α. In: Ayling, J.E., Nair, M.G., Baugh, C.M. (eds) Chemistry and Biology of Pteridines and Folates. Advances in Experimental Medicine and Biology, vol 338. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2960-6_20

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  • DOI: https://doi.org/10.1007/978-1-4615-2960-6_20

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6287-6

  • Online ISBN: 978-1-4615-2960-6

  • eBook Packages: Springer Book Archive

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