Medline ® Abstracts for References 10,11
of 'Hyperimmunoglobulin D syndrome: Pathophysiology'
Isoprenoid biosynthesis in hereditary periodic fever syndromes and inflammation.
Houten SM, Frenkel J, Waterham HR
Cell Mol Life Sci. 2003;60(6):1118.
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.
Laboratory Genetic Metabolic Diseases, Department of Pediatrics, Emma Children's Hospital, and Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. email@example.com
Regulation of the mevalonate pathway.
Goldstein JL, Brown MS
The mevalonate pathway produces isoprenoids that are vital for diverse cellular functions, ranging from cholesterol synthesis to growth control. Several mechanisms for feedback regulation of low-density-lipoprotein receptors and of two enzymes involved in mevalonate biosynthesis ensure the production of sufficient mevalonate for several end-products. Manipulation of this regulatory system could be useful in treating certain forms of cancer as well as heart disease.
Departments of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.