PROPIEDADES ALOSTÉRICAS DE LOS ORTÓLOGOS MAMÍFEROS DE ALOX15

Lipoxygenases (ALOX) are non-heme iron containing dioxygenases that catalyze the oxygenation of polyenoic fatty acid containing lipids to their corresponding hydroperoxy derivatives. These enzymes are widely distributed in highly developed plants and animals. In bacteria they rarely occur but they have not been detected in archaea and viruses. The human genome involves six functional ALOX genes (ALOX15, ALOX15B, ALOX12, ALOX12B, ALOXE3, ALOX5) encoding for six different isoenzymes. The mouse genome carries an orthologous gene for each human ALOX gene but in addition an Aloxe12 gene has been identified in this species. The application of isoenzyme-specific loss-of-function strategies suggested that the coding multiplicity may not be interpreted as sign of functional redundancy. In fact, the different isoenzymes apparently fulfill different biological functions. Mammalian ALOX15 orthologs are allosteric enzymes but the molecular basis for their allosteric properties remains controversial. In fact, two alternative hypotheses (presence of allosteric binding sites at enzyme monomers vs. ALOX15 dimers consist of an allosteric and a catalytic monomer) have been introduced and this review is aimed at critically evaluating the pros and conts of these two mechanistic scenarios.