Clinical and biochemical consequences of p450 oxidoreductase deficiency

Flück, Christa E; Pandey, Amit V (2011). Clinical and biochemical consequences of p450 oxidoreductase deficiency. Endocrine development, 20, pp. 63-79. Basel: Karger

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Patients with P450 oxidoreductase (POR) deficiency typically present with adrenal insufficiency, genital anomalies and bony malformations resembling the Antley-Bixler craniosynostosis syndrome. Since our first report in 2004, more than 40 POR mutations have been identified in over 65 patients. POR is the obligate electron donor to all microsomal P450 enzymes, including the steroidogenic enzymes CYP17A1, CYP21A2 and CYP19A1. POR deficiency may cause disordered sexual development manifested as genital undervirilization in 46, XY newborns as well as overvirilization in those who are 46, XX. This may be explained by impaired aromatization of fetal androgens that may cause maternal virilization and low urinary estriol levels during pregnancy. In addition, the alternate 'backdoor' pathway of androgen biosynthesis, which leads to dihydrotestosterone production bypassing androstenedione and testosterone, may also play a role. Functional assays studying the effects of POR mutations on steroidogenesis showed that several POR variants impaired CYP17A1, CYP21A2 and CYP19A1 activities to different degrees, indicating that each POR variant must be studied separately for each potential target P450 enzyme. POR variants may also affect skeletal development and drug metabolism. As most drugs are metabolized by hepatic microsomal P450 enzymes, studies of the impact of POR mutations on drug-metabolizing P450s are particularly important.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine > Endocrinology/Metabolic Disorders
UniBE Contributor:	Flück Pandey, Christa Emma, Pandey, Amit Vikram
ISSN:	1421-7082
Publisher:	Karger
Language:	English
Submitter:	Amit Vikram Pandey
Date Deposited:	04 Oct 2013 14:13
Last Modified:	02 Mar 2023 23:20
PubMed ID:	21164260
URI:	https://boris.unibe.ch/id/eprint/2818 (FactScience: 205735)