Lipoxygenation in rat brain?
It has been previously claimed that rodent brain possesses lipoxygenase activity, based upon the structure of products which were formed from arachidonic acid and the inhibition of this activity by "lipoxygenase inhibitors." Our studies confirm that various positional isomers of hydroxyeicosatetraenoic acids (HETE) are formed (e.g., 15-, 12-, 11-, 9-, 8- and 5-HETE) by brain homogenate and that their production is inhibited by certain lipoxygenase inhibitors, such as nordihydroguaiaretic acid (NDGA) but not by cyclooxygenase or cytochrome P-450 inhibitors. However, stereochemical analysis indicated racemic distributions of these products suggesting that they were not formed by a lipoxygenase enzyme but rather by a peroxidative process. It should also be noted that the presence of 12(S)-lipoxygenase activity could be demonstrated by stereochemical analysis only when the brain was not perfused properly, indicating this activity was due to blood cell contamination. It is known that many lipoxygenase inhibitors are also capable of inhibiting peroxidative reactions apparently due to their free radical scavenging properties. For these reasons, it is essential that the stereochemical purity of purported lipoxygenase products be determined and that previous claims of lipoxygenase activity in mammalian brain be reexamined.
Kim
H Y
HY
Laboratory of Clinical Studies, DICBR, NIAAA, Bethesda, MD 20892.
Sawazaki
S
S
Salem
N
N
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000302:isolation & purification / Q000378:metabolism; D006893:Hydroxyeicosatetraenoic Acids / Q000302:isolation & purification / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008084:Lipoxygenase / Q000302:isolation & purification / Q000378:metabolism*; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D008730:Methoxsalen / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D015117:5,8,11,14-Eicosatetraynoic Acid; D016718:Arachidonic Acid; D009637:Masoprocol; D003577:Cytochrome P-450 Enzyme System; D011335:Proadifen; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D008730:Methoxsalen; D007213:Indomethacin