Lipoxygenase--a versatile biocatalyst for biotransformation of endobiotics and xenobiotics.
Lipoxygenase, a member of the arachidonate cascade enzymes, dioxygenates polyenoic fatty acids to finally yield products with profound and distinct biological activity. This review summarizes the available evidence for another role played by lipoxygenases in the metabolism of endobiotics and xenobiotics. Although other mechanisms exist, a direct hydrogen abstraction by the enzyme and the peroxyl radical-dependent chemical oxidation appear to be central to the co-oxidase activity of lipoxygenases. Besides polyunsaturated fatty acids, H2O2, fatty acid hydroperoxides, and synthetic organic hydroperoxides support the lipoxygenase-catalyzed xenobiotic oxidation. The major reactions documented thus far include oxidation, epoxidation, hydroxylation, sulfoxidation, desulfuration, dearylation, and N-dealkylation. It is noteworthy that lipoxygenases are also capable of glutathione conjugation of certain xenobiotics. The enzyme system appears to be inducible following exposure to chemicals. Lipoxygenases are inhibited by a large number of chemicals, some of which also serve as co-substrates. Available data suggest that lipoxygenases contribute to in vivo metabolism of xenobiotics in mammals.
Kulkarni
A P
AP
Florida Toxicology Research Center, College of Public Health, University of South Florida, Tampa 33612-3805, USA. akulkarn@hsc.usf.edu
D000818:Animals; D003640:Dealkylation; D004347:Drug Interactions; D004790:Enzyme Induction; D005227:Fatty Acids / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006900:Hydroxylation; D008084:Lipoxygenase / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D015262:Xenobiotics / Q000378:metabolism*
D005227:Fatty Acids; D005609:Free Radicals; D015262:Xenobiotics; D008084:Lipoxygenase; D005978:Glutathione