CYP7B1: One Cytochrome P450, Two Human Genetic Diseases, and Multiple Physiological Functions

Abstract

The CYP7B1 cytochrome P450 enzyme hydroxylates carbons 6 and 7 of the B ring of oxysterols and steroids. Hydroxylation reduces the biological activity of these substrates and facilitates their conversion to end products that are readily excreted from the body. CYP7B1 is expressed in the liver, reproductive tract, and brain and performs different physiological functions in each tissue. Hepatic CYP7B1 activity is crucial for the inactivation of oxysterols and their subsequent conversion into bile salts. Loss of CYP7B1 activity is associated with liver failure in children. In the reproductive tract, the enzyme metabolizes androgens that antagonize estrogen action; mice without CYP7B1 have abnormal prostates and ovaries. The role of CYP7B1 in brain is under investigation; recent studies show that spastic paraplegia type 5, a progressive neuropathy, is caused by loss-of-function mutations in the human gene.

A New Method for Determination the Activity of 25-Hydroxycholesterol 7-Alpha-Hydroxylase (Cyp7b1) in Tissues of Women With Breast Tumors Using Elisa Technique With Some Modification.

“…The development of enzyme-linked immunosorbent assay ELISA through insert external antibody which study the characterization of antibody-antigen interactions in tumor tissues at constant PH 7.4 and temperature 37Cᵒ in different time (1,5,10,15, and 30) in minute result activity of enzyme was increased until 30 minute the incubation was used from the study by Margrit Schwarz that in analyzed by thin-layer chromatography on Silica Gel LK5D 150-Å plates (Whatman) in a solvent system containing toluene/ethyl acetate (13) .…”

“…25-hydroxycholesterol 7α-hydroxylase is a heme-thiolate protein (P-450). Cytochrome P450 enzymes contain a single heme group and give a Soret peak at 450 nm ,is reduced iron forms and bound to CO (carbon monoxide) ,(cytochrome P450, family 7, subfamily B, polypeptide 1) CYP7B1 is a microsomal enzyme that utilizes NADPH-cytochrome P450 reductase as an electron donor and stimulates 7a-hydroxylation of oxysterols and steroids (5) .This enzyme stimulates the following reaction (1) Oxysterol 7α-hydroxylase, is found in a lot of tissues including brain, lung, liver, prostate and kidney is linked with several physiological functions depending on tissue localization, including; 1-Bile acid biosynthesis (6) . 2-Pathway of steroid hormones (including neurosteroids) (7) 3-Regulation of immunoglobulin production (8) .…”

Cytochromes P450: Roles in Diseases

“…These variants are summarized in Ref. 68. Of them, three are nucleotide deletion or insertions in the CYP7B1 coding regions, four are nonsense mutations, and 10 are missense mutations.…”

Tissue-Specific Regulation of Sex Hormone Biosynthesis and Metabolism: Novel Aspects on Hormonal Signalling and Maintenance of Cellular Steroid Levels

“…CYP7B1-mediated catalysis leads to formation of 6-or 7-hydroxymetabolites, mainly 7-hydroxyderivatives Rose et al, 1997;Stiles et al, 2009;Wu et al, 1999) (Fig. 9).…”