Cytochrome P450
CYTOCHROME P450 2S1
Cytochrome P450s (CYPs) are monooxygenase proteins that catalyze the metabolism of exogenous and endogenous substrates. CYPs function as enzymes and are found in all kingdoms of life. The P in P450 refers to pigment and 450nm refers to the wavelength of CYPs in solution exposed to carbon monoxide (CO). CYPs belong to the superfamily of proteins containing a heme (iron) cofactor active site. The heme active site is tethered to the CYP protein via thiolate ligand derived from a cysteine residue.The cysteine and accompanying residues in the C-terminal are highly conserved and contain the PROSITE consensus sequence [FW] - [SGNH] - x - [GD] - {F} - [RKHPT] - {P} - C - [LIVMFAP] - [GAD] [2-8]. The heme is used to oxidize drugs by adding a hydroxyl group to these substances, often as a way to rid the body of potentially harmful toxins in order to make them more water-soluble. They do this by inserting one atom of molecular dioxygen into an organic substrate (RH) while the second oxygen atom is reduced to water (RH+02 + 2e- → ROH + H20). CYP catalysis substrate binding to the heme site requires a two-electron transfer with NADH-cytochrome P450 oxidoreductase (CPR) to the highly reactive iron-oxo intermediate which promotes oxidation and returns the P450 to a resting state. Most CYP’s can bypass CPR by using a peroxide shunt, where single oxygen donors form an iron-oxo intermediate [1].
CYP subfamily IIS, polypeptide 1 (CYP2S1) is the one of newest members of the extrahepatic CYP family [9] and is mainly expressed in tissues such as the lung, intestine, stomach, spleen, skin, breast and kidney. CYP2S1 localize in the endoplasmic reticulum and surrounding microsome membrane. An increased expression of CYP2S1 occurs in several tumors of epithelial origin, and metabolizes eicosanoids in the arachidonic acid pathway [10-13] CYP2S1 expression is elevated in response to known carcinogens including ultraviolet irradiation, coal tar, and dioxin [14]. CYP2S1
Cytochrome P450s (CYPs) are monooxygenase proteins that catalyze the metabolism of exogenous and endogenous substrates. CYPs function as enzymes and are found in all kingdoms of life. The P in P450 refers to pigment and 450nm refers to the wavelength of CYPs in solution exposed to carbon monoxide (CO). CYPs belong to the superfamily of proteins containing a heme (iron) cofactor active site. The heme active site is tethered to the CYP protein via thiolate ligand derived from a cysteine residue.The cysteine and accompanying residues in the C-terminal are highly conserved and contain the PROSITE consensus sequence [FW] - [SGNH] - x - [GD] - {F} - [RKHPT] - {P} - C - [LIVMFAP] - [GAD] [2-8]. The heme is used to oxidize drugs by adding a hydroxyl group to these substances, often as a way to rid the body of potentially harmful toxins in order to make them more water-soluble. They do this by inserting one atom of molecular dioxygen into an organic substrate (RH) while the second oxygen atom is reduced to water (RH+02 + 2e- → ROH + H20). CYP catalysis substrate binding to the heme site requires a two-electron transfer with NADH-cytochrome P450 oxidoreductase (CPR) to the highly reactive iron-oxo intermediate which promotes oxidation and returns the P450 to a resting state. Most CYP’s can bypass CPR by using a peroxide shunt, where single oxygen donors form an iron-oxo intermediate [1].
CYP subfamily IIS, polypeptide 1 (CYP2S1) is the one of newest members of the extrahepatic CYP family [9] and is mainly expressed in tissues such as the lung, intestine, stomach, spleen, skin, breast and kidney. CYP2S1 localize in the endoplasmic reticulum and surrounding microsome membrane. An increased expression of CYP2S1 occurs in several tumors of epithelial origin, and metabolizes eicosanoids in the arachidonic acid pathway [10-13] CYP2S1 expression is elevated in response to known carcinogens including ultraviolet irradiation, coal tar, and dioxin [14]. CYP2S1
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