Abstract
12-Lipoxygenase and cyclooxygenase 1 are the dominating 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)-hydroxyeicosatetraenoic acid to form 5(S),12(S)-dihydroxyeicosatetraenoic 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-lipoxygenase. The presence of albumin reduced the formation of 5(S),12(S)-dihydroxyeicosatetraenoic acid from 5(S)-hydroxyeicosatetraenoic acid, however, it had no effect on the 12(S)-hydroxyeicosatetraenoic acid production from endogenous arachidonic acid. In contrast, when 15(S)-hydroxyeicosatetraenoic acid was incubated with activated platelets, the formation of 14(R),15(S)-dihydroxyeicosatetraenoic acid was stimulated 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 exogenous arachidonic acid (20 μm) to the incubations inverted the effects of albumin on the conversion of 15(S)-hydroxyeicosatetraenoic 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 estimates of the binding constants to albumin were 1.8 × 105 for 15-HETE, 1.4 × 105 for 12-HETE, and 0.9 × 105 for 5-HETE respectively. These results suggest an important role of albumin for the regulation of the availability of substrates for platelet 12-lipoxygenase.—Dadaian, M., and P. Westlund. Albumin modifies the metabolism of hydroxyeicosatetraenoic acids via 12-lipoxygenase in human platelets. J. Lipid Res. 1999. 40: 940–947.
Highlights
12-Lipoxygenase and cyclooxygenase 1 are the dominating enzymes that metabolize arachidonic acid in human platelets
In the present paper we have studied the effect of albumin on the metabolism of 5- and 15(S)-hydroxyeicosatetraenoic acid (15-HETE), as well as 5(S),15(S)-dihydroxyeicosatetraenoic acid (5,15-DHETE) in human platelets
Platelets or aspirin-treated platelets were incubated for 60 min with 10 m or 50 m [3H8]-hydroxyeicosatetraenoic acid (5-HETE) or [3H8]15HETE or 50 m 5,15-DHETE in the presence or absence of 600 m albumin
Summary
12-Lipoxygenase and cyclooxygenase 1 are the dominating enzymes that metabolize arachidonic acid in human platelets. 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-lipoxygenase. It has been known for a long time that albumin can carry fatty acids as a transporter from the peripheral tissue to the liver in which the fatty acids are degraded by -oxidation [12]. Our in vitro data with leukocytes and a combination of leukocytes and platelets clearly showed that exogenously added arachidonic acid is to some extent available for the synthesis of 12-HETE in the presence of albumin, whereas the metabolism of 12-HETE by 5-LO or cytochrome P450 in the leukocytes is almost negligible [14]
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