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 delta13 double bond catalyzed by NADPH/NADH dependent delta13-15-ketoprostaglandin reductase (13-PGR). 13-PGR was also found to exhibit NADP+-dependent leukotriene B4 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 B2 (TXB2) at C-11 catalyzed by NAD+-dependent 11-hydroxythromboxane B2 dehydrogenase (11-TXB2DH). The product of this reaction, 11-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.
Tai
Hsin-Hsiung
HH
Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington 40536-0082, USA. htail@uky.edu
Ensor
Charles Mark
CM
Tong
Min
M
Zhou
Huiping
H
Yan
Fengxiang
F
D011452:15-Oxoprostaglandin 13-Reductase / Q000235:genetics / Q000378:metabolism*; D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D013329:Structure-Activity Relationship
D011453:Prostaglandins; D000429:Alcohol Oxidoreductases; D006911:Hydroxyprostaglandin Dehydrogenases; C049239:thromboxane dehydrogenase; C035859:15-hydroxyprostaglandin dehydrogenase; D011452:15-Oxoprostaglandin 13-Reductase