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Molybdenum in Human Health and Disease

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Interrelations between Essential Metal Ions and Human Diseases

Part of the book series: Metal Ions in Life Sciences ((MILS,volume 13))

Abstract

Molybdenum is an essential trace element and crucial for the survival of animals. Four mammalian Mo-dependent enzymes are known, all of them harboring a pterin-based molybdenum cofactor (Moco) in their active site. In these enzymes, molybdenum catalyzes oxygen transfer reactions from or to substrates using water as oxygen donor or acceptor. Molybdenum shuttles between two oxidation states, MoIV and MoVI. Following substrate reduction or oxidation, electrons are subsequently shuttled by either inter- or intra-molecular electron transfer chains involving prosthetic groups such as heme or iron-sulfur clusters. In all organisms studied so far, Moco is synthesized by a highly conserved multi-step biosynthetic pathway. A deficiency in the biosynthesis of Moco results in a pleitropic loss of all four human Mo-enzyme activities and in most cases in early childhood death. In this review we first introduce general aspects of molybdenum biochemistry before we focus on the functions and deficiencies of two Mo-enzymes, xanthine dehydrogenase and sulfite oxidase, caused either by deficiency of the apo-protein or a pleiotropic loss of Moco due to a genetic defect in its biosynthesis. The underlying molecular basis of Moco deficiency, possible treatment options and links to other diseases, such as neuropsychiatric disorders, will be discussed.

Please cite as: Met. Ions Life Sci. 13 (2013) 415–450

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Acknowledgments

The great work of all current and past postdocs, graduate, master, and bachelor students as well as technicians is gratefully acknowledged. This work would not have been possible without many collaborators that helped to build bridges of true interdisciplinarity. Research funding by the German Science Foundation (DGF), the Federal Ministry of Education and Research (BMBF), the FP7 EU funding (Marie Curie Program), the Fonds der Chemischen Industrie (FCI), and the Center for Molecular Medicine Cologne (CMMC) is gratefully acknowledged.

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  1. Institute of Biochemistry, Department of Chemistry, Center for Molecular Medicine, University of Cologne, Zülpicher Strasse 47, D-50674, Köln, Germany

    Guenter Schwarz & Abdel A. Belaidi

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  1. Guenter Schwarz
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  1. Dept. of Chemistry, Inorganic Chemistry, University of Basel, Basel, Basel Stadt, Switzerland

    Astrid Sigel

  2. Department of Chemistry, Inorganic Chemistry, University of Basel, Basel, Switzerland

    Helmut Sigel

  3. Institute of Inorganic Chemistry, University of Zürich, Zürich, Zürich, Switzerland

    Roland K.O. Sigel

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Schwarz, G., Belaidi, A.A. (2013). Molybdenum in Human Health and Disease. In: Sigel, A., Sigel, H., Sigel, R. (eds) Interrelations between Essential Metal Ions and Human Diseases. Metal Ions in Life Sciences, vol 13. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7500-8_13

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