Cellular and Molecular Life Sciences CMLS

, Volume 60, Issue 6, pp 1118–1134

Isoprenoid biosynthesis in hereditary periodic fever syndromes and inflammation

  • S. M. Houten
  • J. Frenkel
  • H. R. Waterham
Review

DOI: 10.1007/s00018-003-2296-4

Cite this article as:
Houten, S., Frenkel, J. & Waterham, H. CMLS, Cell. Mol. Life Sci. (2003) 60: 1118. doi:10.1007/s00018-003-2296-4

Abstract:

Mevalonate kinase (MK) is an essential enzyme in the isoprenoid biosynthesis pathway which produces numerous biomolecules (isoprenoids) involved in a variety of cellular processes. The indispensability of MK and isoprenoid biosynthesis for human health is demonstrated by the identification of its deficiency as the biochemical and molecular cause of the inherited autoinflammatory disorders mevalonic aciduria and hyperimmunoglobulinemia D and periodic fever syndrome. Since the discovery of the genetic defect, considerable progress has been made in understanding the molecular, biochemical and immunological basis of MK deficiency. Important questions such as which specific protein(s) and/or signaling pathway(s) are affected, however, remain unanswered. Resolving the complete pathophysiology of this disorder is a major challenge, but eventually will give insight into the in vivo role of MK and isoprenoid biosynthesis in inflammation and fever. This may open novel options for antiinflammatory therapies in general. Here, we give a general introduction on isoprenoid biosynthesis, the regulation thereof and deficiencies therein. We review the molecular, biochemical and immunological aspects of MK deficiency and discuss the relations between isoprenoid biosynthesis and inflammation. Finally, we compare MK deficiency with other autoinflammatory syndromes.

Key words: Isoprenoid biosynthesis; mevalonate kinase; hyper-IgD and periodic fever syndrome; mevalonic aciduria; autoinflammatory syndromes; inflammation; fever. 

Copyright information

© Birkhäuser Verlag, 2003

Authors and Affiliations

  • S. M. Houten
    • 1
  • J. Frenkel
    • 2
  • H. R. Waterham
    • 1
  1. 1.Laboratory Genetic Metabolic Diseases, Departments of Pediatrics/Emma Children's Hospital and Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam (The Netherlands)NL
  2. 2.Departments of General Pediatrics and Pediatric Immunology, Wilhelmina Children's Hospital, University Medical Center, Utrecht (The Netherlands)NL
  3. 3.Present address: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS/INSERM/ULP, BP 10142, 67404 Illkirch Cedex (France), Fax: + 33 3 88 65 32 01, e-mail: smhouten@igbmc.u-strasbg.frFR

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