Stereoselective carbonyl reductases from rat skin and leukocyte microsomes converting 12‐ketoeicosatetraenoic acid to 12(S)‐HETE

Abstract
Cell‐free preparations from rat polymorphonuclear leukocytes and skin were found to catalyze the reduction of 12‐keto‐5,8,10,14‐eicosatetraenoic acid (12‐KETE) to 12‐hydroxyeicosatetraenoic acid (12‐HETE). The reductase activity was associated with the microsomal fraction and showed a marked preference for NADH over NADPH as reducing cofactor. Characterization of the reaction product by chiral phase HPLC of the methyl ester derivative indicated that 12‐KETE reduction generated almost exclusively 12(S)‐HETE. The results demonstrate that rat skin and leukocyte microsomes possess an NADH‐dependent 12‐KETE reductase activity that forms 12(S)‐HETE as a major product. The identification of Stereoselective 12‐KETE reductases provides a basis for further defining the role these enzymes may play in the regulation of 12‐KETE levels and in the protection against degradation of 12‐KETE to the pro‐inflammatory 12(R)‐HETE by selectively generating 12‐HETE of the S configuration.

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