TY  - JOUR
PY  - 1996//
TI  - Suicide inactivation of porcine leukocyte 12-lipoxygenase associated with its incorporation of 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid derivative
JO  - Biochimica et biophysica acta
A1  - Kishimoto, K.
A1  - Nakamura, M.
A1  - Suzuki, H.
A1  - Yoshimoto, T.
A1  - Yamamoto, S.
A1  - Takao, T.
A1  - Shimonishi, Y.
A1  - Tanabe, T.
SP  - 56
EP  - 62
VL  - 1300
IS  - 1
N2  - Two isozymes of arachidonate 12-lipoxygenase, platelet-type and leukocyte-type, which were distinguished by their substrate specificities and primary structures, were investigated with reference to 'suicide' inactivation. Upon reaction with arachidonic acid the leukocyte-type enzyme was inactivated rapidly during the catalysis, whereas the platelet-type enzyme did not show such a rapid inactivation. The two 12-lipoxygenase isozymes were incubated with various hydroperoxy and hydroxy products from arachidonic acid. (15S)-Hydroperoxy-5,8,11,13-eicosatetraenoic acid (15-HPETE) was found to be a unique substrate of the leukocyte-type 12-lipoxygenase as follows. (1) 15-HPETE was an active substrate for porcine leukocyte 12-lipoxygenase, and converted anaerobically to a 14,15-epoxy compound (14,15-leukotriene A4). (2) A rapid inactivation of the enzyme was observed within 2 min upon aerobic and anaerobic incubations with 15-HPETE. (3) 15-HPETE was rapidly incorporated into the enzyme in a nearly equimolar amount under both aerobic and anaerobic conditions. (4) Several findings suggested a covalent binding of 15-HPETE or its derivative to the enzyme. (5) Such a rapid and stoichiometric incorporation of 15-HPETE was not observed with the platelet-type 12-lipoxygenase. On the basis of these findings we presumed that 15-HPETE was transformed to 14,15-leukotriene A4, which was covalently bound to the leukocyte-type 12-lipoxygenase leading to the suicide inactivation of the enzyme.<p /> <p>Language: en</p>
LA  - en
SN  - 0006-3002
UR  - http://dx.doi.org/10.1016/0005-2760(95)00241-3
ID  - ref1
ER  -