Disease relevance of Mvk

• In addition, we show that in cells and tissues obtained from patients with peroxisomal deficiency diseases mevalonate kinase protein and its activity are severely reduced [1].
• We report the construction of an expression plasmid for rat mevalonate kinase and the overexpression of recombinant enzyme in Escherichia coli [2].

Psychiatry related information on Mvk

• 2. The levels of mevalonate kinase protein and enzyme activity were determined in the livers of rats treated with either cholesterol-lowering agents (cholestyramine, pravastatin, and lovastatin) or with dietary modifications [3].

High impact information on Mvk

• Endogenous association of LHR mRNA with MVK was assessed by immunoprecipitation of the ribonucleoprotein complex with MVK antibody followed by reverse transcription-PCR of the RNA associated with the immune complex [4].
• Mevalonate kinase catalyzes the ATP-dependent phosphorylation of mevalonic acid to form mevalonate 5-phosphate, a key intermediate in the pathways of isoprenoids and sterols [5].
• Identification and functional characterization of an active-site lysine in mevalonate kinase [2].
• Recombinant rat mevalonate kinase was inactivated by the lysine-specific reagent, pyridoxal phosphate (PLP) [2].
• The data obtained demonstrate that there is only one mevalonate kinase protein that is predominantly localized in peroxisomes [1].

Biological context of Mvk

• To study the role of His20 of mevalonate kinase, a variety of mutant expression plasmids of rat mevalonate kinase including pRMK(H20L), pRMK(H20Y), and pRMK(H20K) were constructed using site-directed mutagenesis, and mutant proteins were overexpressed and purified [6].
• These results represent the first identification of an active-site residue in mevalonate kinase [2].
• The decrease in total PKC activity was accompanied by an increase in Ca2+, phosphatidylserine (PS), diacylglycerol (DG)-insensitive activity suggesting the release of a portion of the catalytic domain of PKC (M-kinase) by the phorbol ester treatment [7].

Anatomical context of Mvk

• Mevalonate kinase is localized in rat liver peroxisomes [8].
• In addition, we present evidence for the unexpected finding that the purified mevalonate kinase (isolated from the cytosol and assumed to be a cytosolic protein) is actually a peroxisomal protein [8].
• These findings suggest that insulin provokes increases in M-kinase in rat adipocytes [9].
• T cells and eosinophils in BAL fluid from mice treated with PS/2 or MK2 were phenotypically different from controls [10].
• Selective decreases of alpha4+ T cells in the BAL fluid after PS/2 or MK2 treatment were coupled with changes in CD8+, CD11a, and CD62L expression [10].

Associations of Mvk with chemical compounds

• Mevalonate kinase plays a key role in regulating the biosynthesis of cholesterol in animal cells [6].
• Mevalonate kinase is believed to be a cytosolic enzyme and catalyzes the phosphorylation of mevalonate to form mevalonate 5-phosphate [8].
• Diets containing cholestyramine alone or cholestyramine and either pravastatin or lovastatin increased mevalonate kinase activity 3-6-fold [3].
• Mevalonate kinase activity decreased approximately 50% in rats treated with diets containing either 5% cholesterol or 5% cholesterol and 0.5% cholic acid [3].
• For instance, mevalonate kinase and phosphomevalonate kinase are almost totally released (95% and 91%, respectively), whereas 3-hydroxy-3-methylglutaryl-CoA reductase is fully retained [11].

Other interactions of Mvk

• In contrast, HCV-polyprotein-(1,189-1,525) activates PKC with increasing Vmax, while it abolishes the substrate inhibition of its catalytical domain (M-kinase) through a mechanism analogous to that of PKA and C subunit [12].
• HMG-CoA reductase kinase: measurement of activity by methods that preclude interference by inhibitors of HMG-CoA reductase activity or by mevalonate kinase [13].
• Studies on mevalonate kinase, phosphomevalonate kinase and pyrophosphomevalonate decarboxylase in developing rat brain [14].
• In contrast, the activities of other enzymes involved in the de novo synthesis of cholesterol, namely acetoacetyl CoA thiolase and HMG CoA synthase, were similar in 2- and 12-month-old rats, while mevalonate kinase activity was significantly lower in the 12-month-old rats [15].

Analytical, diagnostic and therapeutic context of Mvk

• The purified mevalonate kinase had a dimeric structure composed of identical subunits, and the Mr of the enzyme determined by gel chromatography was 86,000 [3].
• Phosphorylation of intact C/EBP from liver nuclear extract by PKC or M-kinase occurred at Ser299 and Ser277 and at an additional site, as demonstrated by immunoprecipitation and peptide mapping [16].
• PS/2, R1-2, or MK2 significantly inhibited the recruitment of eosinophils and lymphocytes into the bronchoalveolar lavage (BAL) fluid and decreased inflammation in the lung tissues [10].

References