background:
Cytochrome P450 1B1 is a key enzyme involved in the production of potentially carcinogenic estrogen metabolites and the activation of environmental carcinogens and is the predominant member of the CYP1 family expressed in normal breast tissue and breast cancer. Estrogen has been proposed to trigger breast cancer development via an initiating mechanism involving its metabolite, catechol estrogen (CE). CYP1B1 catalyzes the conversion of 17-beta-estradiol to the catechol estrogen metabolites 2-OH-E2 and 4-OH-E2 which have both been postulated to be involved in mammary carcinogenesis.
Genetic polymorphisms in CYP1B1 may play an important role in human prostate carcinogenesis as well. Polymorphism of the CYP1B1 gene at codon 432 (Val-->Leu) is associated with a change in catalytic function.
Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Participates in the metabolism of an as-yet-unknown biologically active molecule that is a participant in eye development.
Subcellular Location:
Endoplasmic reticulum membrane. Microsome membrane.
Tissue Specificity:
Expressed in many tissues.
DISEASE:
Defects in CYP1B1 are the cause of primary congenital glaucoma type 3A (GLC3A) [MIM:231300]. GLC3A is an autosomal recessive form of primary congenital glaucoma (PCG). PCG is characterized by marked increase of intraocular pressure at birth or early childhood, large ocular globes (buphthalmos) and corneal edema. It results from developmental defects of the trabecular meshwork and anterior chamber angle of the eye that prevent adequate drainage of aqueous humor.
Defects in CYP1B1 are a cause of primary open angle glaucoma (POAG) [MIM:137760]. POAG is a complex and genetically heterogeneous ocular disorder characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. The disease is asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place. In some cases, POAG shows digenic inheritance involving mutations in CYP1B1 and MYOC genes.
Defects in CYP1B1 are a cause of Peters anomaly (PAN) [MIM:604229]. Peters anomaly is a congenital defect of the anterior chamber of the eye.
Similarity:
Belongs to the cytochrome P450 family.
Database links:
UniProtKB/Swiss-Prot: Q16678.2
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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