There are many P450 enzymes. If I remember correctly the main one for the majority of prescription half life creation is CYP3A4.
Here is the meat of the journal article:
Published today in the journal Cell, the study details how in response to acidity cells turn off a critical molecular switch known as mTORC1 that, in ordinary conditions, gauges the availability of nutrients before giving cells the green light to grow and divide. That event, Dang and his colleagues show, shuts down the cell’s production of proteins, disrupting their metabolic activity and circadian clocks, and pushing them into a quiescent state. They also demonstrate that this acid-mediated effect might be relatively easy to reverse — a finding that could help improve a variety of cancer therapies.
“In tumors grafted into mice, we see mTOR activity in spotty places where there’s oxygen,” says Dang who is also a professor in the Molecular and Cellular Oncogenesis Program at The Wistar Institute. “But if you add baking soda to the drinking water given to those mice, the entire tumor lights up with mTOR activity. The prediction would be that by reawakening these cells, you could make the tumor far more sensitive to therapy.”
The researchers show that in acidic conditions protein motors propel lysosomes carrying mTOR away from the area around the nucleus, where they’re ordinarily located. This separates mTOR from a protein required for its activation, RHEB, which continues to hang around at that location. Lacking one of its key activation signals, mTOR remains dormant, suspending the synthesis of proteins — including the components of the cell’s molecular clock — along with most metabolic activity.
“Cells don’t want to make proteins or other biomolecules when they’re under stress,” says Dang. “They want to slow things down and only awaken when things return to normal.”
The researchers show that baking soda can reverse this effect. When given to mice in their drinking water, it surprisingly sufficed to neutralize the acidity of hypoxic patches in tumors. This sent lysosomes zipping back to the nuclear periphery in cells — where RHEB was waiting — and restored the activity of mTOR.
All this is relevant to cancer because researchers have long known that quiescent cells cannot typically be killed by chemotherapy. Notably, Dang and his team also found that T cell activation, which is essential to most immunotherapies, is similarly compromised under acidic conditions.
“We started out with a question about oxygen starvation and the circadian clock, and we ended up discovering a new mechanism by which acidic conditions in tissues shut off a lot of things — including the cell’s molecular clock,” muses Dang.
Here is an abstract feom an old Mycology Journal
Cytochromes of fungi are essentially similar to those of animals. Cytochromes of fungi constitute two electron transport systems occurring in mitochondria and the endoplasmic reticulum. The former system, called the respiratory chain, contributes to cellular respiration and ATP generation, whereas the later system, named the microsomal electron transport system, is responsible for biosynthesis of several cellular components.
The oxidative metabolism of lanosterol, that is included in the biosynthetic pathway of ergosterol, is one of the important functions of the microsomal electron transport system, which is catalyzed by P450(14DM). Many azole antifungal agents avidly combine with P450(14DM) and inhibit the oxidative removal of C-32 (the 14 alpha-demethylation) of lanosterol. This inhibition causes depletion of ergosterol and accumulation of 14-methylsterols in the membrane of fungal cells. Such change in sterol composition disturbs membrane function and results in growth inhibition and death of the fungal cells. Accordingly, P450(14DM) is considered as the primary target for azole antifungal agents.
If azole antifungal agents inhibit mammalian cytochrome P450 too, their systemic use may result in potentially significant adverse reactions. The high selectivity of azole antifungal agents for fungal P450(14DM) will be necessary for their systemic application. Binding ability of an azole antifungal agent to P450(14DM) is predominantly determined by the substituent at N-1 of the azole group, and the substituent must interact with the substrate site of the cytochrome.
Extensive modification of the N-1 substituents and the screening of newly developed compounds with respect to the selectivity to fungal P450(14DM) with some conventional methods will be necessary. For this project, a biochemical understanding of cytochrome P450 and other cytochromes is important.