Recombinant Rat Cytochrome P450 1A1 (Cyp1a1)

Function

A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins. 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 (CPR; NADPH-ferrihemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds. Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C15alpha and C16alpha positions (By similarity). Displays different regioselectivities for polyunsaturated fatty acids (PUFA) hydroxylation (By similarity). Catalyzes the epoxidation of double bonds of certain PUFA (PubMed:20972997). Converts arachidonic acid toward epoxyeicosatrienoic acid (EET) regioisomers, 8,9-, 11,12-, and 14,15-EET, that function as lipid mediators in the vascular system. Displays an absolute stereoselectivity in the epoxidation of eicosapentaenoic acid (EPA) producing the 17(R),18(S) enantiomer (By similarity). May play an important role in 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). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (By similarity)

Subcellular Location

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

Tissue Specificity

Liver

Subunit

Both Cytochrome P450MT2A and Cytochrome P450MT2B interact with cytosolic chaperones HSP70 and HSP90; this interaction is required for initial targeting to mitochondria. P450MT2B interacts (via mitochondrial targeting signal) with TOMM40 (via N-terminus); this interaction is required for translocation across the mitochondrial outer membrane

Pathway

Cofactor metabolism; retinol metabolism

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• Addya S. et al. Targeting of NH2-terminal-processed microsomal protein to mitochondria: a novel pathway for the biogenesis of hepatic mitochondrial P450MT2. — J. Cell Biol. (1997)
• Anandatheerthavarada H.K. et al. Mitochondrial targeting of cytochrome P450 proteins containing NH2-terminal chimeric signals involves an unusual TOM20/TOM22 bypass mechanism. — J. Biol. Chem. (2009)