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Underestimated reactions and regulation patterns of adrenal cytochromes P450
- Source :
- Molecular and cellular endocrinology. 530
- Publication Year :
- 2020
-
Abstract
- Although cytochrome P450 (CYP) systems including the adrenal ones are being investigated since many years, there are still reactions and regulation patterns that have been underestimated ever since. This review discusses neglected ones to bring them into the focus of investigators working in the field. Novel substrates and reactions described for adrenal CYPs recently point to the fact that different from what has been believed for many years, adrenal CYPs are less selective than previously thought. The conversion of steroid sulfates, intermediates of steroid biosynthesis as well as of exogenous compounds are being discussed here in more detail and consequences for further studies are drawn. Furthermore, it was shown that protein-protein interactions may have an important effect not only on the activity of adrenal CYPs, but also on the product pattern of the reactions. It was found that, as expected, the stoichiometry of CYP:redox partner plays an important role for tuning the activity. In addition, competition between different CYPs for the redox partner and for electrons and possible alterations by mutants in the efficiency of electron transfer play an important role for the activity and product pattern. Moreover, the influence of phosphorylation and small charged molecules like natural polyamines on the activity of adrenal systems has been demonstrated in-vitro indicating a possible regulation of adrenal CYP reactions by affecting redox partner recognition and binding affinity. Finally, an effect of the genetic background on the consequences of mutations in adrenal CYPs found in patients was suggested from corresponding in-vitro studies indicating that a different genetic background might be able to significantly affect the activity of a CYP mutant.
- Subjects :
- 0301 basic medicine
medicine.drug_class
medicine.medical_treatment
030209 endocrinology & metabolism
Steroid biosynthesis
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Endocrinology
Cytochrome P-450 Enzyme System
Adrenal Glands
medicine
Humans
Steroid 11-beta-hydroxylase
Molecular Biology
Aldosterone
biology
Chemistry
Sulfates
Cholesterol side-chain cleavage enzyme
Cytochrome P450
enzymes and coenzymes (carbohydrates)
Steroid hormone
030104 developmental biology
Gene Expression Regulation
CYP17A1
Mineralocorticoid
Mutation
biology.protein
Steroids
Oxidation-Reduction
Subjects
Details
- ISSN :
- 18728057
- Volume :
- 530
- Database :
- OpenAIRE
- Journal :
- Molecular and cellular endocrinology
- Accession number :
- edsair.doi.dedup.....662e4c0ad65b2e80c529c0281e80be08