Heme dioxygenases reaction mechanism

The enzymatic reaction mechanism was determined by incubating a-carotene 6, a non-symmetric substrate of the enzyme, under a 02 atmosphere in H2 0 followed by isolation and characterization of derivatives of the cleavage product 2 (6). Accordingly, the enzyme cleaving the central double bond of 1 was found to be a non-heme iron monooxygenase (P-carotene 15,15 -monooxygenase) and not dioxygenase as termed earlier (Fig. 3). From the chemical point of view this enzymatic reaction is very unusual for various reasons (i) the reaction... 

Scheme 3. Previous proposals (5,21,49) for the reaction mechanism in the heme dioxygenases via either Criegee (blue) or dioxetane (red) pathways.

Scheme 4. The variously proposed alternative reaction mechanisms for heme dioxygenases, (a) The base-catalyzed abstraction mechanism (21,49). (b) An alternative to the base-catalyzed mechanism, using proton abstraction by the bound O2 (23,27). (c) Electrophilic addition (31,50,51). (d) Radical addition (50-53). The majority opinion from crystallography (27), mass spectrometry (30), mutagenesis (54), and computational work (50) concludes that (a) and (b) are unlikely. It is not yet known whether addition at C or is most likely both have been suggested (31,50-53,55).

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