NADPH—hemoprotein reductase explained

In enzymology, a NADPH—hemoprotein reductase is an enzyme that catalyzes the chemical reaction

\rightleftharpoons NADP⁺ + n reduced hemoprotein

The three substrates of this enzyme are NADPH, H⁺, and oxidized hemoprotein, whereas its two products are NADP⁺ and reduced hemoprotein. It has two cofactors: flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN).

This enzyme belongs to the family of oxidoreductases, specifically those acting on NADH or NADPH with a heme protein as acceptor. The systematic name of this enzyme class is NADPH:hemoprotein oxidoreductase. Other names include cytochrome P450 reductase, ferrihemoprotein P-450 reductase, and NADPH-dependent cytochrome c reductase.

Structural studies

As of late 2007, 10 structures have been solved for this class of enzymes, with PDB accession codes,,,,,,,,, and .

References

• Haas E, Horecker BL, Hogness TR . 1940 . The enzymatic reduction of cytochrome c, cytochrome c reductase . J. Biol. Chem. . 136 . 747 - 774 . 10.1016/S0021-9258(18)73034-2 . free .
• Horecker BL . 1950 . Triphosphopyridine nucleotide-cytochrome c reductase in liver . J. Biol. Chem. . 183 . 2 . 593 - 605 . 10.1016/S0021-9258(19)51185-1 . free .
• Lu AY, Junk KW, Coon MJ . 1969 . Resolution of the cytochrome P-450-containing omega-hydroxylation system of liver microsomes into three components . J. Biol. Chem. . 244 . 3714 - 21 . 4389465 . 13 . 10.1016/S0021-9258(18)83427-5 . free .
• GIBSON QH, PALMER G, WHARTON DC . Studies on the Mechanism of Microsomal Triphosphopyridine Nucleotide-Cytochrome C Reductase . 1965 . J. Biol. Chem. . 240 . 2 . 921 - 31 . 10.1016/S0021-9258(17)45262-8 . 14275154 . free .
• WILLIAMS CH Jr . KAMIN H . 1962 . Microsomal triphosphopyridine nucleotide-cytochrome c reductase of liver . J. Biol. Chem. . 237 . 2 . 587 - 95 . 10.1016/S0021-9258(18)93967-0 . 14007123 . free .
• Masters BS, Bilimoria MH, Kamin H, Gibson QH . Bettie Sue Masters. 1965 . The mechanism of 1- and 2-electron transfers catalyzed by reduced triphosphopyridine nucleotide-cytochrome c reductase . J. Biol. Chem. . 240 . 4081 - 8 . 4378860 . 10 . 10.1016/S0021-9258(18)97152-8 . free .
• Sevrioukova IF, Peterson JA . 1995 . NADPH-P-450 reductase: structural and functional comparisons of the eukaryotic and prokaryotic isoforms . Biochimie . 77 . 562 - 72 . 8589067 . 10.1016/0300-9084(96)88172-7 . 7–8 .
• Wang M, Roberts DL, Paschke R, Shea TM, Masters BS, Kim JJ . 1997 . Three-dimensional structure of NADPH-cytochrome P450 reductase: prototype for FMN- and FAD-containing enzymes . Proc. Natl. Acad. Sci. U.S.A. . 94 . 8411 - 6 . 9237990 . 10.1073/pnas.94.16.8411 . 16 . 22938 . 1997PNAS...94.8411W . free .
• Munro AW, Noble MA, Robledo L, Daff SN, Chapman SK . 2001 . Determination of the redox properties of human NADPH-cytochrome P450 reductase . Biochemistry . 40 . 1956 - 63 . 11329262 . 10.1021/bi001718u . 7 .
• Munro AW, Noble MA, Robledo L, Daff SN, Chapman SK . 2001 . Determination of the redox properties of human NADPH-cytochrome P450 reductase . Biochemistry . 40 . 1956 - 63 . 11329262 . 10.1021/bi001718u . 7 .
• Scrutton NS . 2003 . Electron transfer in human cytochrome P450 reductase . Biochem. Soc. Trans. . 31 . 497 - 501 . 12773143 . 10.1042/BST0310497 . Grunau . A . Paine . M . Munro . AW . Wolf . CR . Roberts . GC . Scrutton . NS . Pt 3 .
• Scrutton NS . 2003 . Electron transfer in human cytochrome P450 reductase . Biochem. Soc. Trans. . 31 . 497 - 501 . 12773143 . 10.1042/BST0310497 . Grunau . A . Paine . M . Munro . AW . Wolf . CR . Roberts . GC . Scrutton . NS . Pt 3 .