I am working on a project about CYPs 450. It seems that most of them function as monooxygenases but there are other categories as well.

Assuming that the question makes sense, is it correct to say that CYP 450 monooxygenases always require the presence of a regenerating system (NADPH) as opposed to other CYPs 450 which are NOT functioning as monooxygenases?


2 Answers 2


I would say this is not a correct statement. The main reason being that just because an enzyme is not a monooxygenase doesn't mean it doesn't require a regenerating system for NADPH.
Examples would be many dehydrogenase, hydroxylase and synthase enzymes. They also require NADPH regenerating systems to operate efficiently. So, one of the CYP 450 enzymes may fall into any of these categories requiring NADPH/NADP yet not be a monooxygenase.

  • $\begingroup$ Thank you for your response. What about the other way round? If it requires NADPH/NAD is it a monooxygenase? $\endgroup$ Commented Jun 29, 2018 at 11:45
  • 1
    $\begingroup$ No! As stated in my previous response, many other enzymes that are NOT monooxygenases DO require NADPH/NADP. If you mean to ask "If it is a monooxygenase, does it mean it requires NADPH/NADP?", then I believe the answer would be "yes". There may be exceptions, but none that I'm aware of. $\endgroup$
    – Dr. J.
    Commented Jun 29, 2018 at 12:41

OP's concern: Monooxygenases always require the presence of a regenerating system ($\mathrm{NADPH}$).

It is true that most Monooxygenases are nicotinamide adenine dinucleotide ($\mathrm{NADP^+}$ and its reduced form, $\mathrm{NADPH}$) dependent (Wikipedia). Monooxygenases catalyzes the incorporation of a hydroxyl group into a variety of substrates by catalyzing the reduction of $\ce{O2}$ to $\ce{H2O}$ while oxidizing $\mathrm{NADPH}$.

However, there are some exceptions such as Peptidylglycine $\alpha$-hydroxylating monooxygenase (PHM) and dopamine beta-monooxygenase (DBM). For example, PHM is a copper-, $\ce{O2}$-, and ascorbate-dependent enzyme responsible for the oxidative cleavage of C-terminal glycine-extended precursor peptides to the active $\alpha$-amidated peptide and glyoxylate (Ref.1,2):

The reactions catalyzed by PHM and PAL

There has also been a significant interest in describing the interactions of copper-containing enzymes with $\ce{O2/H2O2}$-derived species. The short-lived intermediates resulting from the activation of dioxygen are the key players in the mechanistic cycles in many of these metalloenzymes. For instance, In the enzyme PHM, various reduced $\ce{Cu/O2}$ species have been proposed to act as catalytically competent intermediates, yet their exact nature and their role in the enzymatic reaction is still unknown. Schismatic diagrams of recent computational mechanistic studies of PHM is shown as snapshot in three stages (Ref.3):

The structure of the reactant, transition state, and intermediate

DBM is also a $\ce{Cu}$ containing mettaloenzyme, following similar mechanism of PHM. The three substrates of DBM are dopamine, ascorbic acid (Vitamin C), and $\ce{O2}$ and products are norepinephrine (from dopamine and $\ce{O2}$), dehydroascorbate (from Vitamin C), and $\ce{H2O}$ (from $\ce{O2}$).


  1. Betty A. Eipper, Richard E. Mains, Christopher C. Glembotski, "Identification in pituitary tissue of a peptide $\alpha$-amidation activity that acts on glycine-extended peptides and requires molecular oxygen, copper, and ascorbic acid," Proc. Natl. Acad. Sci. USA 1983, 80(16), 5144–5148 (https://doi.org/10.1073/pnas.80.16.5144).
  2. A. F. Bradbury, M. D. A. Finnie, D. G. Smyth, "Mechanism of C-terminal amide formation by pituitary enzymes," Nature 1982, 298, 686–688 (https://doi.org/10.1038/298686a0).
  3. Enrique Abad, Judith B. Rommel, Johannes Kästner, "Reaction Mechanism of the Bicopper Enzyme Peptidylglycine $\alpha$-Hydroxylating Monooxygenase," Journal of Biological Chemistry 2014, 289(20), 13726–13738 (doi: 10.1074/jbc.M114.558494).

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