The increased cholesterol substrate leads to increased archaeal growth and digoxin synthesis leading to metabolic channeling to the mevalonate
Identification, evolution, and essentiality of the mevalonate
pathway for isopentenyl diphosphate biosynthesis in Gram-positive cocci.
The archaeal DXP and mevalonate
pathway metabolites can bind [gamma][delta] TCR and digoxin induced calcium signaling can activate NFKB producing chronic immune activation or systemic inflammatory reaction [2,33].
The archaea evolved into gram negative and gram positive bacteria with a mevalonate
pathway which had an evolutionary advantage.
The polyketide biosynthetic pathway appears to be responsible for most of the classes of lichen compounds, whereas pulvinic acids are shikimate derivatives, and the abundance of di- and triterpenoids found in lichens are formed via the mevalonate
Brown, "Regulation of the Mevalonate
Pathway," Nature 343, 425-430 (1990).
Squalene synthase inhibitors held the theoretical promise of having fewer side-effects than statins, as they do not deplete the mevalonate
pool and so should not interfere with isoprenoid synthesis.
Clinical, biochemical, and molecular analysis of mevalonate
Both cholesterol and CoQ10 share a common biosynthetic pathway, which involves the formation of mevalonate
compound with the aid of 3-hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase.
As a result, there is depletion of certain substances, eg, ubiquinone and mevalonate
blocks synthesized by the mevalonate
or methylerythritol 4-phosphate
through relatively simple adaptations of fatty acid biosynthesis, the mevalonate
pathway, or through simple transformations of host precursors (5).