Recombinant Rat Cytochrome P450 1B1 (Cyp1b1)

Function

A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (By similarity). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (By similarity). Exhibits catalytic activity for the formation of hydroxyestrogens from 17beta-estradiol (E2), namely 2- and 4-hydroxy E2 (PubMed:23821647). Metabolizes testosterone and progesterone to B or D ring hydroxylated metabolites (By similarity). May act as a major enzyme for all-trans retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (By similarity). Catalyzes the epoxidation of double bonds of certain PUFA. Converts arachidonic acid toward epoxyeicosatrienoic acid (EpETrE) regioisomers, 8,9-, 11,12-, and 14,15- EpETrE, that function as lipid mediators in the vascular system (PubMed:20972997). Additionally, displays dehydratase activity toward oxygenated eicosanoids including hydroperoxyeicosatetraenoates (HpETEs). This activity is independent of cytochrome P450 reductase, NADPH, and O2 (By similarity). Also involved in the oxidative metabolism of xenobiotics, particularly converting polycyclic aromatic hydrocarbons and heterocyclic aryl amines procarcinogens to DNA-damaging products (By similarity). Plays an important role in retinal vascular development. Under ambient/hyperoxic O2 conditions, promotes angiogenesis and capillary morphogenesis of retinal endothelial cells and pericytes, likely by metabolizing the oxygenated products symptomatic of oxidative stress (By similarity). Also, contributes to oxidative homeostasis and ultrastructural organization and function of trabecular meshwork tissue through modulation of POSTN expression (By similarity)

Subcellular Location

Endoplasmic reticulum membrane (Peripheral membrane protein); Microsome membrane (Peripheral membrane protein); Mitochondrion

Pathway

Lipid metabolism; arachidonate metabolism

• Bhattacharyya K.K. et al. Identification of a rat adrenal cytochrome P450 active in polycyclic hydrocarbon metabolism as rat CYP1B1. Demonstration of a unique tissue-specific pattern of hormonal and aryl hydrocarbon receptor-linked regulation. — J. Biol. Chem. (1995)
• Walker N.J. et al. Rat CYP1B1: an adrenal cytochrome P450 that exhibits sex-dependent expression in livers and kidneys of TCDD-treated animals. — Carcinogenesis (1995)
• Mesaros C. et al. Analysis of epoxyeicosatrienoic acids by chiral liquid chromatography/electron capture atmospheric pressure chemical ionization mass spectrometry using [13C]-analog internal standards. — Rapid Commun. Mass Spectrom. (2010)
• Jacob A. et al. Aryl hydrocarbon receptor-dependent upregulation of Cyp1b1 by TCDD and diesel exhaust particles in rat brain microvessels. — Fluids Barriers CNS (2011)
• Deb S. et al. Estradiol-mediated suppression of CYP1B1 expression in mouse MA-10 Leydig cells is independent of protein kinase A and estrogen receptor. — Mol. Cell. Biochem. (2011)
• Brauze D. et al. The effect of aryl hydrocarbon receptor ligands on the expression of polymerase (DNA directed) kappa (Polkappa), polymerase RNA II (DNA directed) polypeptide A (PolR2a), CYP1B1 and CYP1A1 genes in rat liver. — Environ. Toxicol. Pharmacol. (2012)
• Nishida C.R. et al. Specificity determinants of CYP1B1 estradiol hydroxylation. — Mol. Pharmacol. (2013)