the resulting mobility of the substrate during catalysis might be designed specifically
to promote release of free radical intermediates leading to undirected lipid perox-
idation (Brash, 1999). Under aerobic conditions molecular oxygen reacts with
the radical to form a hydroperoxy radical (Figure 1, step c). Subsequently, the
Fe(II) will be oxidized to Fe(III) (Figure 1, step d) and the hydroperoxide anion
is protonated. The final reaction product dissociates from the catalytically active
Fe(III)-LOX; this concludes the catalytic cycle and the next substrate molecule
can be bound.
According to an alternative model (Corey and Nagata, 1987), an electrophilic
addition of Fe(III) to C 1 of the (1Z,4Z)-pentadiene system may occur, forming an
organoiron-intermediate. This process is followed by a stereoselective abstraction
of a proton from the bisallylic methylene. Then molecular dioxygen reacts with
the bisallylic organoiron-intermediate via d-bond insertion forming the
(1S,2E,4Z)-1-hydroperoxy-2,4-pentadiene and the Fe(III)-LOX. In the organoiron
model, regio- and stereoselectivity of dioxygen insertion is controlled by the
Fe(III)-C 1 bond. In contrast, steric factors controlling the binding of the carbon-cen-
tered fatty acid radical at the enzyme and/or the geometry of the diffusion path of
dioxygen appear to be of relevance for the radical mechanism. It should be stressed
that both the radical and the organoiron mechanism may explain most of the me-
15.2 LOXs are versatile catalysts 311
Figure 1. Catalytic cycle of LOXs according to De Groot et al. (1975) and Hilbers et al. (1995).