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Interaction between the two metabolic pathways can be studied by using 13 C-glucose isotopomers. [10] In higher plants, the MEP pathway operates in plastids while the mevalonate pathway operates in the cytosol. [9] Examples of bacteria that contain the MEP pathway include Escherichia coli and pathogens such as Mycobacterium tuberculosis.
Mevalonic acid is a precursor in the biosynthetic pathway known as the mevalonate pathway that produces terpenes and steroids. Mevalonic acid is the primary precursor of isopentenyl pyrophosphate (IPP), that is in turn the basis for all terpenoids. Mevalonic acid is chiral and the (3R)-enantiomer is the only one that is biologically active.
As the second enzyme in the Mevalonate pathway, it catalyzes the phosphorylation of Mevalonic acid to produce Mevalonate-5-phosphate. [8] 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. [9]
The mevalonate pathway (MVA pathway or HMG-CoA reductase pathway) and the MEP pathway are metabolic pathways for the biosynthesis of isoprenoid precursors: IPP and DMAPP. Whereas plants use both MVA and MEP pathway, most organisms only use one of the pathways for the biosynthesis of isoprenoid precursors.
Experiments have demonstrated that glucose and cholesterol homeostasis are regulated by statins. The HMG-CoA reductase (HMGCR), converts HMG-CoA into mevalonic acid. Thus, when HMGCR activities are reduced, the cell associated cholesterols are also reduced. This results in the activation of SREBP-2-mediated signaling pathways.
β-Hydroxy β-methylglutaryl-CoA (HMG-CoA), also known as 3-hydroxy-3-methylglutaryl coenzyme A, is an intermediate in the mevalonate and ketogenesis pathways. It is formed from acetyl CoA and acetoacetyl CoA by HMG-CoA synthase. The research of Minor J. Coon and Bimal Kumar Bachhawat in the 1950s at University of Illinois led to its discovery.
The biosynthesis of terpenoids occurs via the methylerythritol phosphate (MEP) and mevalonic acid(MVA) pathways [7] both of which include isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) as key components. [20]
Isopentenyl pyrophosphate (IPP, isopentenyl diphosphate, or IDP) [1] is an isoprenoid precursor. IPP is an intermediate in the classical, HMG-CoA reductase pathway (commonly called the mevalonate pathway) and in the non-mevalonate MEP pathway of isoprenoid precursor biosynthesis.