mevalonate

In plants, mevalonate is the precursor of all isoprenoid compounds.

Statin drugs might decrease the level of mevalonate and are presently being investigated.

Phosphomevalonic acid is an intermediate in the Mevalonate pathway.

Through 13C-labeling patterns, it has been determined that both the mevalonate and deoxyxylulose pathways are involved in the formation of β-sitosterol.

Some bacteria, such as Pseudomonas mevalonii, can use mevalonate as the sole carbon source.

As predicted by this model, we observed that statin-activated shedding was abolished by adding mevalonate.

Reduction in synthesis of mevalonate leads to decreased generation of a number of isoprenoid lipid derivatives.

In further support of a role for isoprenoids, we were able to demonstrate that supplementation of cells with mevalonate abolished statin-activated shedding (see Figure 4).

Statins block HMGCoA reductase generation of mevalonate from 3-hydroxy-methyl-glutarate (see Figure 7).

Drugs, such as the statins, stop the production of mevalonate by inhibiting HMG-CoA reductase.

Cholesterol occurs naturally in eukaryote cell membranes where it is bio-synthesised from mevalonate via a squalene cyclisation of terpenoids.

Thioesters are common intermediates in many biosynthetic reactions, including the formation and degradation of fatty acids and mevalonate, precursor to steroids.

HIDS is associated with decreased activity of the enzyme mevalonate kinase (MVK).

He received a Borden Award in Nutrition in 1958 for discovering mevalonic acid, or mevalonate, a key compound from which cholesterol is synthesized.

The required isopentenyl pyrophosphate is obtained from the mevalonate (MVA) pathway, which is derives from acetyl-CoA in the cytosol.

Therefore, the addition of mevalonate would be predicted to antagonize statin action via the isoprenoid pathway, by relieving statin-induced mevalonate deficiency.

Acetoacetyl CoA is the precursor of HMG-CoA in the Mevalonate pathway, which is essential for cholesterol synthesis.

Note that, in the HMG-CoA reductase/mevalonate pathway, the precursors already contain a pyrophosphate group, and isoprenoids are produced with a pyrophosphate group.

The resulting mevalonate is then sequentially phosphorylated by two separate kinases, mevalonate kinase and phosphomevalonate kinase, to form 5-pyrophosphomevalonate.

The reduction of HMG-CoA to mevalonate is regulated by feedback inhibition by sterols and non-sterol metabolites derived from mevalonate, including cholesterol.

Class II HMG-CoA reductases catalyse the reverse reaction of class I enzymes, namely the NAD-dependent synthesis of HMG-CoA from mevalonate and CoA.

This team reasoned that certain microorganisms may produce inhibitors of the enzyme to defend themselves against other organisms, as mevalonate is a precursor of many substances required by organisms for the maintenance of their cell wall (ergosterol) or cytoskeleton (isoprenoids).

Dr. Kilara said he and two colleagues had isolated the compound, which he calls Inhibitor of Mevalonate Incorporation to Cholesterol, or IMIC, after they noticed that adults had lower blood cholesterol levels after being fed milk.

Mevalonate kinase deficiency causes an accumulation of mevalonic acid in the urine, resulting from insufficient activity of the enzyme mevalonate kinase (ATP:mevalonate 5-phosphotransferase; EC 2.7.1.36).

Because statins are similar to HMG-CoA on a molecular level, they take the place of HMG-CoA in the enzyme and reduce the rate by which it is able to produce mevalonate, the next molecule in the cascade that eventually produces cholesterol, as well as a number of other compounds.