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Molecular Pharmacology

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Abstract

Two sites of azo reduction in the monooxygenase system.

F J Peterson, J L Holtzman, D Crankshaw and R P Mason
Molecular Pharmacology October 1988, 34 (4) 597-603;
F J Peterson
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J L Holtzman
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D Crankshaw
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R P Mason
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Abstract

The mechanism of the azo reduction of sulfonazo III and amaranth by the rat hepatic monooxygenase system was studied. Air strongly inhibited (greater than 95%) the enzymatic reduction of both azo compounds; a 100% CO atmosphere inhibited amaranth reduction (greater than 90%) but only slightly inhibited sulfonazo III reduction (13%). The addition of 50 microM sulfonazo III to microsomal incubations stimulated oxygen consumption, NADPH oxidation, and adrenochrome formation, whereas 100 microM amaranth did not. The reduction potentials of these two azo compounds were also very different (amaranth, E = -0.620 V; sulfonazo III, E = -0.265 V versus normal hydrogen electrode). The organic mercurial mersalyl converted cytochrome P-450 to cytochrome P-420 (68%) and markedly decreased NADPH-cytochrome P-450(c) reductase activity (97%) in microsomal preparations, presumably by inactivating or destroying functional sulfhydryl groups important for the catalytic activity of these enzymes. GSH was used to restore, and NADP+ to protect, the activities of the monooxygenase components from the effects of mersalyl. The data indicate that inactivation of NADPH-cytochrome P-450(c) reductase inhibits sulfonazo III and amaranth reduction, whereas inactivation of cytochrome P-450 inhibits only amaranth reduction. Furthermore, the reduction of sulfonazo III by purified microsomal NADPH-cytochrome P-450(c) reductase was significantly faster than the rate of reduction of amaranth. These studies demonstrate that two distinct sites of azo reduction exist in the monooxygenase system and that not all azo compounds are reduced by cytochrome P-450.

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Molecular Pharmacology
Vol. 34, Issue 4
1 Oct 1988
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Abstract

Two sites of azo reduction in the monooxygenase system.

F J Peterson, J L Holtzman, D Crankshaw and R P Mason
Molecular Pharmacology October 1, 1988, 34 (4) 597-603;

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Abstract

Two sites of azo reduction in the monooxygenase system.

F J Peterson, J L Holtzman, D Crankshaw and R P Mason
Molecular Pharmacology October 1, 1988, 34 (4) 597-603;
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