Albumin modifies the metabolism of hydroxyeicosatetraenoic acids via 12-lipoxygenase in human platelets.

Lipoxygenase and cyclooxygenase 1 are the dom- inating enzymes that metabolize arachidonic acid in human platelets. In addition to the conversion of arachidonic acid to 12(S)-hydroxyeicosatetraenoic acid, 12-lipoxygenase can also utilize 5(S)-hydroxyeicosatetraenoic acid and 15(S)-hydroxy- eicosatetraenoic acid to form 5(S),12(S)-dihydroxyeicosatet- raenoic acid and 14(R),15(S)-dihydroxyeicosatetraenoic acid, respectively. Furthermore, 15(S)-hydroxyeicosatetraenoic acid works as an inhibitor for 12-lipoxygenase. In the present paper we have studied the influence of albumin on the in vitro metabolism of 5- and 15-hydroxyeicosatetraenoic acids, and 5,15-dihydroxyeicosatetraenoic acid by the platelet 12-lipoxy- genase. The presence of albumin reduced the formation of 5(S),12(S)- dihydroxyeicosatetraenoic acid from 5(S)-hydroxy- eicosatetraenoic acid, however, it had no effect on the 12(S)- hydroxyeicosatetraenoic acid production from endogenous arachidonic acid. In contrast, when 15(S)-hydroxyeicosatet- raenoic acid was incubated with activated platelets, the forma- tion of 14(R),15(S)-dihydroxyeicosatetraenoic acid was stimu- lated by the presence of albumin. Furthermore, albumin reduced the inhibitory action 15(S)-hydroxyeicosatetraenoic acid had on 12(S)-hydroxyeicosatetraenoic acid formation from endogenous arachidonic acid. However, addition of ex- ogenous arachidonic acid (20 m M ) to the incubations inverted the effects of albumin on the conversion of 15(S)-hydroxyeico- satetraenoic acid to 14(R),15(S)-dihydroxyeicosatetraenoic acid and the production of 12(S)-hydroxyeicosatetraenoic acid in these incubations. Based on the Scatchard equation, the esti- mates of the binding constants to albumin were 1.8 3 10 5 for 15-HETE, 1.4 3 10 5 for 12-HETE, and 0.9 3 10 5 for 5-HETE respectively. These results suggest an important role of al- bumin for the regulation of the availability of substrates for platelet 12-lipoxygenase. —Dadaian, M., and P. Westlund. Albu- min modifies the metabolism of hydroxyeicosatetraenoic acids via 12-lipoxygenase in human platelets. J. Lipid Res. 1999. 40: 940-947.