Prostaglandin catabolizing enzymes

The primary catabolic pathway of prostaglandins and related eicosanoids is initiated by the oxidation of 15(S)-hydroxyl group catalyzed by NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) followed by the reduction of A 13 double bond catalyzed by NADPH/NADH dependent Delta(13)-15-ketoprostaglandin reductase (13-PGR). 13-PGR was also found to exhibit NADP(+)-dependent leukotriene B-4 12-hydroxydehydrogenase (12-LTB4DH) activity. These enzymes are considered to be the key enzymes responsible for biological inactivation of prostaglandins and related eicosanoids. A separate catabolic pathway of thromboxane involves the oxidation of thromboxane B-2 (TXB2) at C-I I catalyzed by NAD(+)-dependent I-hydroxythromboxane B2 dehydrogenase (11-TXB2DH). The product of this reaction, I I-dehydro-TXB2, has been considered to be a more reliable quantitative index of thromboxane formation in the circulation. Recent biochemical and molecular biological studies have revealed interesting catalytic properties, structure, and activity relationship, and regulation of gene expression of these three enzymes. Future investigation may shed more light on the roles of these enzymes in health and diseases. (C) 2002 Elsevier Science Inc. All rights reserved.