title: Biochemical and genetic aspects of mevalonate kinase and its deficiency.
abstract: Mevalonate kinase (MK) is an essential enzyme in the mevalonate pathway which produces numerous cellular isoprenoids. The enzyme has been characterized both at the biochemical and the molecular level in a variety of organisms. Despite the fact that mevalonate kinase is not the rate-limiting enzyme in isoprenoid biosynthesis, its activity is subject to feedback regulation by the branch-point intermediates geranyldiphosphate, farnesyldiphosphate and geranylgeranyldiphosphate. Recently, the importance of mevalonate kinase was demonstrated by the identification of its deficiency as the biochemical and molecular cause of the inherited human disorders mevalonic aciduria and hyperimmunoglobulinemia D and periodic fever syndrome. The pathophysiology of these disorders is not yet understood, but eventually will give insight into the in vivo role of mevalonate kinase and isoprenoid biosynthesis with respect to the acute phase response and fever. The subcellular localization of mevalonate kinase is still a matter of debate. The enzyme could be localized predominantly in the cytosol, or in peroxisomes, or it is associated differentially with peroxisomes. Here we review the biochemical and molecular properties of MK, and discuss its biological significance, the regulation of its enzyme activity and finally its subcellular localization.
authors: Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE, Amsterdam, The Netherlands.
authors: S M
authors: SM
authors: Houten
authors: R J
authors: RJ
authors: Wanders
authors: H R
authors: HR
authors: Waterham
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D010505:Familial Mediterranean Fever / Q000209:etiology; D006801:Humans; D006942:Hypergammaglobulinemia / Q000209:etiology; D007072:Immunoglobulin D / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008798:Mevalonic Acid / Q000652:urine; D008969:Molecular Sequence Data; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000172:deficiency / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D016415:Sequence Alignment; D013347:Subcellular Fractions / Q000201:enzymology
chemical_list: D004791:Enzyme Inhibitors; D007072:Immunoglobulin D; D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase; D008798:Mevalonic Acid