Evidence for Protein Radical-Mediated Nuclear Tunneling in Fatty Acid α-Oxygenase

摘要

The a oxidation of fatty acids is associated with essential metabolic, protective, and cell signaling functions in higher organisms.12 Here we provide evidence for an a oxidation mechanism involving a protein-derived radical. The reaction of interest is the first step in eq 1 where 2-R-hydroperoxide compounds are formed upon insertion of O_2 into fatty acid C_α-H bonds. In heme-containing dioxygenases, such as rice α-oxygenase (RαO), the catalytic oxidant is proposed to be a tyrosyl radical. This idea derives from (ⅰ) the homology of RαO to cyclooxygenases (COX-1 and COX-2) believed to use a Tyr· to oxidize arachidonic acid to prostaglandin H~3 and (ⅱ) the loss of activity upon mutation of the conserved Tyr379 to Phe.