Mitenkähän rautapitoisen P450 sytokromin käy Sars2 tulehduksesa?

 Miten p 450 syntyy kehossa?
https://www.sciencedirect.com/science/article/pii/S2095311914609801
 https://doi.org/10.1016/S2095-3119(14)60980-1
 Abstract

The cytochrome P450 (CYP) superfamily is the largest enzymatic protein family in plants, and it also widely exists in mammals, fungi, bacteria, insects and so on. Members of this superfamily are involved in multiple metabolic pathways with distinct and complex functions, playing important roles in a vast array of reactions. As a result, numerous secondary metabolites are synthesized that function as growth and developmental signals or protect plants from various biotic and abiotic stresses. Here, we summarize the characterization of CYPs, as well as their phylogenetic classification. We also focus on recent advances in elucidating the roles of CYPs in mediating plant growth and development as well as biotic and abiotic stresses responses, providing insights into their potential utilization in plant breeding.

  Nomenclature and phylogenetic classification of cytochrome P450s 

The CYP superfamily is an ancient superfamily that has been identified in all domains of organisms such as plants, animals, fungi, protists, archaea, bacteria and even viruses (Lamb et al. 2009). CYPs, which strongly absorb 450 nm light, were first recognized by Martin Klingenberg’s (1958)  group..

 Ref.

Nebert D W, Russell D W. 2002. Clinical importance of the cytochromes P450. Lancet, 360, 1155–1162.

. 2002 Oct 12;360(9340):1155-62. doi: 10.1016/S0140-6736(02)11203-7.

Clinical Importance of the Cytochromes P450

Daniel W Nebert  ¹ , David W Russell

• PMID: 12387968
• DOI: 10.1016/S0140-6736(02)11203-7

The human cytochrome P450 (CYP) superfamily comprises 57 genes. These genes code for enzymes that can have a role in: metabolism of drugs, foreign chemicals, arachidonic acid and eicosanoids; cholesterol metabolism and bile-acid biosynthesis; steroid synthesis and metabolism; vitamin D ₃ synthesis and metabolism; retinoic acid hydroxylation; and those of still unknown function. Cytochrome P450 was once believed to be mainly a hepatic drug detoxication system, but is now understood to include a myriad of enzymic reactions implicated in important life processes. Mutations in many CYP genes cause inborn errors of metabolism and contribute to many clinically relevant diseases. 


P450 on jo  SARS-2 infektion alkupään tekijän nsp2 kohdemolekyyli.

 Katson tässä  tavallisia  lääkemolekyylejä jotka vaikuttavat p450- sytokromiin.

Pharmacologic Interactions

Shoshana Zevin, in Cardiac Intensive Care (Third Edition), 2019

Pharmacokinetic interactions.

Cytochrome P-450 enzyme inducers (e.g., rifampin, phenytoin, phenobarbital) decrease the bioavailability and increase the clearance of verapamil and diltiazem. St. John's wort also significantly decreases verapamil bioavailability through induction of first-pass metabolism in the gut.¹³⁴ Conversely, the enzyme inhibitor cimetidine increases the bioavailability and decreases the clearance of calcium antagonists.^135–137 Macrolide antibiotics clarithromycin and telithromycin also inhibit CYP3A4; their combination with verapamil may result in significant verapamil toxicity.^138,139 Felodipine metabolism is inhibited by itraconazole and erythromycin, resulting in significant increases in plasma concentrations and AUC.^68,140

Grapefruit juice, which inhibits some P-450 enzymes, has been found to increase the bioavailability of some dihydropyridine calcium antagonists. The most significant interaction was with felodipine and nitrendipine, whereas nifedipine bioavailability was not significantly affected.¹⁴¹ Verapamil increases digoxin concentration by inhibiting its renal excretion through P-gp.¹⁴² Diltiazem has been reported to increase digoxin concentration, but this effect is not always present, and digoxin levels are affected to a lesser degree than with verapamil.¹³⁵ Nifedipine does not have a significant effect on digoxin concentration.¹⁴³

Verapamil and diltiazem are inhibitors of CYP3A4 and thus are expected to inhibit the clearance of drugs metabolized by this enzyme. Verapamil and diltiazem significantly increase peak plasma levels and AUC of simvastatin and atorvastatin,^144–146 and there are reports of rhabdomyolysis with these combinations.^147,148 Verapamil and diltiazem have been reported to increase cyclosporine plasma levels, necessitating a reduction of cyclosporine doses.^149,150 The same interaction was observed between diltiazem and sirolimus¹⁵¹ and diltiazem and tacrolimus.^152,153 Verapamil has also been reported to increase blood levels of prazosin. This pharmacokinetic interaction, along with a possible pharmacodynamic interaction, may result in hypotension.¹⁵⁴ Verapamil inhibits theophylline metabolism.¹⁵⁵ Verapamil and diltiazem significantly decrease the metabolism of midazolam, potentially causing excessive sedation. They also inhibit the metabolism of the anticonvulsants carbamazepine and phenytoin.^156,157

Because verapamil is highly bound to plasma proteins, its displacement can result in transient toxicity. Complete AV block has been precipitated by ceftriaxone and clindamycin, which are also highly bound drugs, in a patient receiving verapamil.¹