Mevalonate Pathway Analysis Service

Mevalonate Pathway

Mevalonate pathway, also known as HMG-CoA reductase  pathway or the isoprenoid pathway, is an important metabolic pathway  essential in eukaryotes, archaea, and some bacteria. The  mevalonate pathway is widely studied. This pathway is widely known being  involved in cardiovascular diseases. Recently, a large number of experimental  and clinical studies show that inhibition of non-sterol isoprenoids has  important therapeutical implications. By synthesizing sterol isoprenoids, such  as cholesterol, and non-sterol isoprenoids, this pathway plays an essential  role in various cellular processes. Starting with acetyl-CoA, the mevalonate  pathway ends with two five-carbon building blocks names as isopentenyl  pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) used  for making isoprenoids like cholesterol, coenzyme Q10, and  all steroid hormones. This pathway, specifically HMG-CoA reductase in  the mevalonate pathway, is a well-known target of a class of cholesterol  lowering drugs—statins. Statins inhibits the activity of HMG-CoA reductase, and  thereby inhibits the generation of cholesterol- one kind of isoprenoids.

The mevalonate pathway starts with the two consecutive  enzyme catalyzed steps conversion from three acetyl-CoAs into 3-hydroxy-3-methylglutaryl-CoA  (HMG-CoA). The rate-limiting enzyme of the pathway, HMG-CoA reductase is then  converts the HMG-CoA to mevalonate (MVA). 5-pyrophosphomevalonate (MVAPP) is  generated after MVA is phosphorylated twice. The decarboxylation of MVAPP leads  to the formation of IPP.

The mevalonate pathway plays a key role in cellular  metabolism and is responsible for conversion of acetyl-CoA to isopentenyl  5-diphosphate, which is the precursor of various polyisoprenoid metabolites and  natural products. These polyisoprenoid metabolites and natural products act a  number of different functions. Besides generating various sterols for the  synthesis of hormones, bile acids and oxysterols, the pathway also generates a  wide range of non-sterol isoprenoids with various structures and functions,  which are derived from isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate  (DMAPP). Heme A acts in the mitochondrial respiratory chain, side chains of  ubiquinone-10, isopentenyl-tRNA involved in protein translation, dolichol  essential for protein glycosylation are examples of those non-sterol  isoprenoids. These non-sterol isoprenoids are potential therapeutic targets for  many diseases such as oncology, autoimmune disorders and Alzheimer disease.

In literature, a large number of detection methods for  intermediates involved in the mevalonate pathway have been described. However,  only one intermediate can be determined in most of these described methods,  such as MVA in human urine and plasma and DMAPP in plant leaves. Though  simultaneous determination of FPP and GGPP in rat liver and cultured NIH3T3  cells has been described, the simultaneous determination of all the  intermediates in the mevalonate pathway remains a challenge. That’s because the  intermediates involved in the mevalonate pathway are dramatically different in  structure and physical properties. McCaskill and Croteau described a  simultaneous radiolabeled quantification procedure for the analysis of all 11  intermediates of the mevalonate pathway in plant cells.

With no use of radioactive or fluorescent compounds, here  Creative Proteomics develops a sensitive high performance liquid  chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the direct  detection and quantification of all intermediates in the mevalonate  pathway. 



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Mevalonate Pathway Metabolites Quantified in This Service

With integrated set of  separation, characterization, identification and quantification systems featured with  excellent robustness & reproducibility, high and ultra-sensitivity,  Creative Proteomics provides reliable, rapid and cost-effective  mevalonate pathway targeted metabolomics services.

* For Research Use Only. Not for use in diagnostic procedures.
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