Data delineating the relationship between disorders of cholesterol metabolism and elevated blood pressure (BP) do not exist. We postulated that mevalonate, the metabolic precursor of endogenous cholesterol and the direct product of 3-hydroxy-3-methylglutaryl-CoA reductase, was a contributing factor for the maintenance of vascular tone and systemic BP. We conducted in vivo, ex vivo, and in vitro...

A latex pellet fraction from Euphorbia lathyris incorporates mevalonate into triterpenols and their fatty acid esters. Conditions for improved incorporation were determined. CaCl(2) or CaCl(2) plus MnCl(2) stimulated biosynthesis, and the metal ion chelator, ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA) enhanced stimulation. Ethylenediaminetetraacetic acid was almost as effective as EG...

Abstract Background Isoprenoids are the most ancient and essential class of metabolites produced in all organisms, either via mevalonate (MVA)-and/or methylerythritol phosphate (MEP)-pathways. The MEP-pathway is present plastid-bearing organisms eubacteria. However, no comprehensive study reveals origination evolutionary characteristics genes eukaryotes. Results Here, detailed bioinformatics an...

Simvastatin has been shown to have anti-inflammatory effects that are independent of its serum cholesterol lowering action, but the mechanisms by which these anti-inflammatory effects are mediated have not been elucidated. To explore the mechanism involved, the effect of simvastatin on Toll-like receptor (TLR) signalling in primary human monocytes was investigated. A short pre-treatment with si...

Three analogues of mevalonic acid have been found to inhibit cholesterol biosynthesis in liver homogenates in the following order of efficacy: 3-methyl-3-hydroxy pentanoic acid > A*3methyl pentenoic acid > As-3-methyl pentenoic acid. The hydroxy acid produces half the maximum inhibition at a concentration of 5 pmoles/ml of homogenate. This corresponds to a ratio of 100 pmoles of inhibitor to 1 ...

3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is a critical enzyme in the mevalonate pathway that regulates the biosynthesis of cholesterol as well as isoprenoids that mediate the membrane association of certain GTPases. Blockade of this enzyme by atorvastatin (AT) inhibits the destructive proinflammatory T helper cell (Th)1 response during experimental autoimmune encephalomyelitis ...

BACKGROUND Juvenile hormones (JH) regulate development and reproductive maturation in insects. JHs are synthesized through the mevalonate pathway (MVAP), an ancient metabolic pathway present in the three domains of life. Mevalonate kinase (MVK) is a key enzyme in the MVAP. MVK catalyzes the synthesis of phosphomevalonate (PM) by transferring the γ-phosphoryl group from ATP to the C5 hydroxyl ox...

Introduction Malaria is one of the world’s most serious parasitic diseases. There are estimated 300-500 million cases and more than a million deaths from malaria each year. Human malaria is caused by infection with intracellular parasites of the genus Plasmodium that are transmitted by Anopheles mosquitoes. Plasmodium falciparum is the most lethal among the four species of Plasmodium that infec...

Deregulation of the cholesterol pathway is an anomaly observed in human diseases, many of which have in common neurological involvement and unknown pathogenesis. In this study we have used Mevalonate Kinase Deficiency (MKD) as a disease-model in order to investigate the link between the deregulation of the mevalonate pathway and the consequent neurodegeneration. The blocking of the mevalonate p...

Numerous integral membrane proteins are degraded in the mammalian ER. HMG-CoA reductase (HMG-R), a key enzyme in the mevalonate pathway by which isoprenoids and sterols are synthesized, is one substrate of ER degradation. The degradation of HMG-R is modulated by feedback signals from the mevalonate pathway. We investigated the role of regulated degradation of the two isozymes of HMG-R, Hmg1p an...