Monooxygenase NADPH cosubstrate

Cytochromes P450 are monooxygenases whose cosubstrates, often NADH or NADPH, deliver electrons to the active center heme via a separate flavoprotein and often via an iron-sulfur protein as well 476a b A typical reaction (Eq. 18-55) is the 11 (3-hydroxylation of a steroid, an essential step in the biosynthesis of steroid hormones (Fig. 22-11). The hydroxyl group is introduced without inversion of configuration. The same enzyme converts unsaturated derivatives to epoxides (Eq. 18-56), while other cytochromes P450... 

FIGURE 21-37 Ring closure converts linear squalene to the condensed steroid nucleus. The first step in this sequence is catalyzed by a mixed-function oxidase (a monooxygenase), for which the cosubstrate is NADPH. The product is an epoxide, which in the next step is cyclized to the steroid nucleus. The final product of these reactions in animal cells is cholesterol in other organisms, slightly different sterols are produced, as shown. 

Question Why do monooxygenase reactions require NADPH as a cosubstrate ... 

FIGURE 8.28 Phenylalanine and tyrosine catabolism. Phenylalanine is converted to tyrosine by phenylalanine monooxygenase. This enzyme requires tetrahydrobiopterin as a cofactor. This cofactor is synthesized in the body from GTP and must be in the fully reduced, tetrahydro form to be active. The cofactor is converted to the dihydro form in the course of the reaction. A separate enzyme, which uses NADPH as a reducing agent, catalyzes the reduction of dihydroprotein back to tetrahydrobiopterin. Oxygen is the cosubstrate of phenylalanine monooxygenase, as well as of two other enzymes, in the pathway shown. 

NADPH can serve as a cosubstrate of flavoprotein monooxygenase by first reducing the flavin, after which the reduced flavin can react with O2 to generate the hydroxylating reagent. An example is the bacterial 4-hydroxybenzoate hydroxylase which forms... 

The major steps in the catalytic cycle for FMO are shown in Figure 10.18 (45,46). Like most of the other monooxygenases, FMO requires NADPH and oxygen as cosubstrates to catalyze the oxidation of the xenobiotic... 

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