oxygenase

An oxygenase is an enzyme that catalyzes the incorporation of molecular oxygen (O2) into an organic substrate. In many monooxygenases, one atom of O2 is incorporated into the substrate while the other is reduced to water. In dioxygenases, both atoms of O2 are transferred to the substrate. Oxygenases thus facilitate the introduction of oxygen into chemical structures, enabling a wide range of metabolic transformations.

Oxygenases are commonly divided into monooxygenases and dioxygenases. Monooxygenases, such as cytochrome P450 enzymes and flavin-containing monooxygenases, typically require cofactors such as NADPH and flavin or heme groups. They insert a single oxygen atom into the substrate while reducing the second to water. Dioxygenases, including alpha-ketoglutarate–dependent dioxygenases and non-heme iron dioxygenases, incorporate both oxygen atoms into the substrate; many use metal centers to activate O2.

Mechanisms vary by subclass. Cytochrome P450 enzymes form a reactive iron-oxo species that abstracts hydrogen and hydroxylates substrates. Alpha-ketoglutarate–dependent dioxygenases oxidize substrates via an iron(II)-oxo species generated with AKG, yielding products plus succinate and CO2. Lipoxygenases and other oxygenases that do not rely on P450 expand the range of substrates and reactions.

Role and applications: Oxygenases participate in primary and secondary metabolism, including drug and steroid metabolism, biosynthesis of lipids, vitamins, and signaling molecules. They are important in bioremediation and industrial biocatalysis. In pharmacology, CYP enzymes influence drug metabolism and detoxification, while aberrant oxygenase activity can contribute to oxidative stress and disease.