Mevalonate kinase explained

Mevalonate kinase is an enzyme (specifically a kinase) that in humans is encoded by the MVK gene.^{[1] [2]} Mevalonate kinases are found in a wide variety of organisms from bacteria to mammals. This enzyme catalyzes the following reaction:

.

Function

Mevalonate is a key intermediate, and mevalonate kinase a key early enzyme, in isoprenoid and sterol synthesis.^[1] As the second enzyme in the Mevalonate pathway, it catalyzes the phosphorylation of Mevalonic acid to produce Mevalonate-5-phosphate.^[3] A reduction in mevalonate kinase activity to around 5-10% of its typical value is associated with the mevalonate kinase deficiency (MVD) resulting in accumulation of intermediate mevalonic acid.^[4]

Clinical significance

Defects can be associated with hyperimmunoglobulinemia D with recurrent fever.

Mevalonate kinase deficiency caused by mutation of this gene results in mevalonic aciduria, a disease characterized psychomotor retardation, failure to thrive, hepatosplenomegaly, anemia and recurrent febrile crises. Defects in this gene also cause hyperimmunoglobulinaemia D and periodic fever syndrome, a disorder characterized by recurrent episodes of fever associated with lymphadenopathy, arthralgia, gastrointestinal dismay and skin rash.^[1] The symptoms of the disease typically start at infancy and may be additionally triggered by stress or bacterial infection. Children with mevalonate kinase deficiency may remain undiagnosed for a long time as there is not enough scientific data at the moment to accurately diagnose children with the disease.

See also

• Mevalonic aciduria
• Mevalonic acid

References

Further reading

• Ma J, Dempsey AA, Stamatiou D, Marshall KW, Liew CC . Identifying leukocyte gene expression patterns associated with plasma lipid levels in human subjects . Atherosclerosis . 191 . 1 . 63–72 . March 2007 . 16806233 . 10.1016/j.atherosclerosis.2006.05.032 .
• Willer CJ, Sanna S, Jackson AU, Scuteri A, Bonnycastle LL, Clarke R, Heath SC, Timpson NJ, Najjar SS, Stringham HM, Strait J, Duren WL, Maschio A, Busonero F, Mulas A, Albai G, Swift AJ, Morken MA, Narisu N, Bennett D, Parish S, Shen H, Galan P, Meneton P, Hercberg S, Zelenika D, Chen WM, Li Y, Scott LJ, Scheet PA, Sundvall J, Watanabe RM, Nagaraja R, Ebrahim S, Lawlor DA, Ben-Shlomo Y, Davey-Smith G, Shuldiner AR, Collins R, Bergman RN, Uda M, Tuomilehto J, Cao A, Collins FS, Lakatta E, Lathrop GM, Boehnke M, Schlessinger D, Mohlke KL, Abecasis GR . 6 . Newly identified loci that influence lipid concentrations and risk of coronary artery disease . Nature Genetics . 40 . 2 . 161–9 . February 2008 . 18193043 . 5206900 . 10.1038/ng.76 .
• Naruto T, Nakagishi Y, Mori M, Miyamae T, Imagawa T, Yokota S . Hyper-IgD syndrome with novel mutation in a Japanese girl . Modern Rheumatology . 19 . 1 . 96–9 . 2009 . 18941711 . 10.1007/s10165-008-0130-4 . 25331505 .
• Krisans SK . The role of peroxisomes in cholesterol metabolism . American Journal of Respiratory Cell and Molecular Biology . 7 . 4 . 358–64 . October 1992 . 1356376 . 10.1165/ajrcmb/7.4.358 .
• Houten SM, Wanders RJ, Waterham HR . Biochemical and genetic aspects of mevalonate kinase and its deficiency . Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids . 1529 . 1–3 . 19–32 . December 2000 . 11111075 . 10.1016/s1388-1981(00)00135-9 .
• Fu Z, Voynova NE, Herdendorf TJ, Miziorko HM, Kim JJ . Biochemical and structural basis for feedback inhibition of mevalonate kinase and isoprenoid metabolism . Biochemistry . 47 . 12 . 3715–24 . March 2008 . 18302342 . 10.1021/bi7024386 .
• Kathiresan S, Willer CJ, Peloso GM, Demissie S, Musunuru K, Schadt EE, Kaplan L, Bennett D, Li Y, Tanaka T, Voight BF, Bonnycastle LL, Jackson AU, Crawford G, Surti A, Guiducci C, Burtt NP, Parish S, Clarke R, Zelenika D, Kubalanza KA, Morken MA, Scott LJ, Stringham HM, Galan P, Swift AJ, Kuusisto J, Bergman RN, Sundvall J, Laakso M, Ferrucci L, Scheet P, Sanna S, Uda M, Yang Q, Lunetta KL, Dupuis J, de Bakker PI, O'Donnell CJ, Chambers JC, Kooner JS, Hercberg S, Meneton P, Lakatta EG, Scuteri A, Schlessinger D, Tuomilehto J, Collins FS, Groop L, Altshuler D, Collins R, Lathrop GM, Melander O, Salomaa V, Peltonen L, Orho-Melander M, Ordovas JM, Boehnke M, Abecasis GR, Mohlke KL, Cupples LA . 6 . Common variants at 30 loci contribute to polygenic dyslipidemia . Nature Genetics . 41 . 1 . 56–65 . January 2009 . 19060906 . 2881676 . 10.1038/ng.291 .
• Hager EJ, Gibson KM . Mevalonate kinase deficiency and autoinflammation . The New England Journal of Medicine . 357 . 18 . 1871–2 . November 2007 . 17978300 . 10.1056/NEJMc072799 . free .
• Marques-Vidal P, Bochud M, Paccaud F, Waterworth D, Bergmann S, Preisig M, Waeber G, Vollenweider P . 6 . No interaction between alcohol consumption and HDL-related genes on HDL cholesterol levels . Atherosclerosis . 211 . 2 . 551–7 . August 2010 . 20430392 . 10.1016/j.atherosclerosis.2010.04.001 .
• Lu Y, Dollé ME, Imholz S, van 't Slot R, Verschuren WM, Wijmenga C, Feskens EJ, Boer JM . 6 . Multiple genetic variants along candidate pathways influence plasma high-density lipoprotein cholesterol concentrations . Journal of Lipid Research . 49 . 12 . 2582–9 . December 2008 . 18660489 . 10.1194/jlr.M800232-JLR200 . free .
• Samkari A, Borzutzky A, Fermo E, Treaba DO, Dedeoglu F, Altura RA . A novel missense mutation in MVK associated with MK deficiency and dyserythropoietic anemia . Pediatrics . 125 . 4 . e964-8 . April 2010 . 20194276 . 10.1542/peds.2009-1774 . 24915125 .
• Nakayama K, Bayasgalan T, Yamanaka K, Kumada M, Gotoh T, Utsumi N, Yanagisawa Y, Okayama M, Kajii E, Ishibashi S, Iwamoto S . 6 . Large scale replication analysis of loci associated with lipid concentrations in a Japanese population . Journal of Medical Genetics . 46 . 6 . 370–4 . June 2009 . 19487539 . 10.1136/jmg.2008.064063 . 35374041 .
• Koné-Paut I, Sanchez E, Le Quellec A, Manna R, Touitou I . Autoinflammatory gene mutations in Behçet's disease . Annals of the Rheumatic Diseases . 66 . 6 . 832–4 . June 2007 . 17213252 . 1954666 . 10.1136/ard.2006.068841 .
• Weissglas-Volkov D, Aguilar-Salinas CA, Sinsheimer JS, Riba L, Huertas-Vazquez A, Ordoñez-Sánchez ML, Rodriguez-Guillen R, Cantor RM, Tusie-Luna T, Pajukanta P . 6 . Investigation of variants identified in caucasian genome-wide association studies for plasma high-density lipoprotein cholesterol and triglycerides levels in Mexican dyslipidemic study samples . Circulation: Cardiovascular Genetics . 3 . 1 . 31–8 . February 2010 . 20160193 . 2827864 . 10.1161/CIRCGENETICS.109.908004 .
• Simon A, van der Meer JW, Vesely R, Myrdal U, Yoshimura K, Duys P, Drenth JP . Approach to genetic analysis in the diagnosis of hereditary autoinflammatory syndromes . Rheumatology . 45 . 3 . 269–73 . March 2006 . 16234278 . 10.1093/rheumatology/kei138 . free .
• Gattorno M, Sormani MP, D'Osualdo A, Pelagatti MA, Caroli F, Federici S, Cecconi M, Solari N, Meini A, Zulian F, Obici L, Breda L, Martino S, Tommasini A, Bossi G, Govers A, Touitou I, Woo P, Frenkel J, Koné-Paut I, Baldi M, Ceccherini I, Martini A . 6 . A diagnostic score for molecular analysis of hereditary autoinflammatory syndromes with periodic fever in children . Arthritis and Rheumatism . 58 . 6 . 1823–32 . June 2008 . 18512793 . 10.1002/art.23474 . 11368/2299050 . free .
• Fogarty MP, Xiao R, Prokunina-Olsson L, Scott LJ, Mohlke KL . Allelic expression imbalance at high-density lipoprotein cholesterol locus MMAB-MVK . Human Molecular Genetics . 19 . 10 . 1921–9 . May 2010 . 20159775 . 2860891 . 10.1093/hmg/ddq067 .
• Nair AK, Young MA, Menon KM . Regulation of luteinizing hormone receptor mRNA expression by mevalonate kinase--role of the catalytic center in mRNA recognition . The FEBS Journal . 275 . 13 . 3397–407 . July 2008 . 18494797 . 10.1111/j.1742-4658.2008.06490.x . 25641224 . free .
• Deo RC, Reich D, Tandon A, Akylbekova E, Patterson N, Waliszewska A, Kathiresan S, Sarpong D, Taylor HA, Wilson JG . 6 . Genetic differences between the determinants of lipid profile phenotypes in African and European Americans: the Jackson Heart Study . PLOS Genetics . 5 . 1 . e1000342 . January 2009 . 19148283 . 2613537 . 10.1371/journal.pgen.1000342 . free .
• Junyent M, Parnell LD, Lai CQ, Lee YC, Smith CE, Arnett DK, Tsai MY, Kabagambe EK, Straka RJ, Province M, An P, Borecki I, Ordovás JM . 6 . Novel variants at KCTD10, MVK, and MMAB genes interact with dietary carbohydrates to modulate HDL-cholesterol concentrations in the Genetics of Lipid Lowering Drugs and Diet Network Study . The American Journal of Clinical Nutrition . 90 . 3 . 686–94 . September 2009 . 19605566 . 2728650 . 10.3945/ajcn.2009.27738 .

External links

• • PDBe-KB provides an overview of all the structure information available in the PDB for Human Mevalonate kinase

Notes and References

1. Web site: Entrez Gene: mevalonate kinase.
2. Schafer BL, Bishop RW, Kratunis VJ, Kalinowski SS, Mosley ST, Gibson KM, Tanaka RD . Molecular cloning of human mevalonate kinase and identification of a missense mutation in the genetic disease mevalonic aciduria . The Journal of Biological Chemistry . 267 . 19 . 13229–38 . July 1992 . 10.1016/S0021-9258(18)42199-0 . 1377680 . free .
3. Mulders-Manders CM, Simon A . Hyper-IgD syndrome/mevalonate kinase deficiency: what is new? . Seminars in Immunopathology . 37 . 4 . 371–6 . July 2015 . 25990874 . 4491100 . 10.1007/s00281-015-0492-6 .
4. Stabile A, Compagnone A, Napodano S, Raffaele CG, Patti M, Rigante D . Mevalonate kinase genotype in children with recurrent fevers and high serum IgD level . Rheumatology International . 33 . 12 . 3039–42 . December 2013 . 23239036 . 10.1007/s00296-012-2577-z . 3220012 .