The phenomenon of chirality has been shown to greatly impact drug activities and effects. Different enantiomers may exhibit different effects in a certain biological condition or disease state. Cytochrome P450 (CYP) enzymes metabolize arachidonic acid (AA) into a large variety of metabolites with a wide range of activities. Hydroxylation of AA by CYP hydroxylases produces hydroxyeicosatetraenoic acids (HETEs), which are classified into mid-chain (5, 8, 9, 11, 12, and 15-HETE), subterminal (16-, 17-, 18- and 19-HETE) and terminal (20-HETE) HETEs. Except for 20-HETE, these metabolites exist as a racemic mixture of R and S enantiomers in the physiological system. The two enantiomers could have different degrees of activity or sometimes opposing effects. In this review article, we aimed to discuss the role of mid-chain and subterminal HETEs in different organs, importantly the heart and the kidneys. Moreover, we summarized their effects in some conditions such as neutrophil migration, inflammation, angiogenesis, and tumorigenesis, with a focus on the reported enantiospecific effects. We also reported some studies using genetically modified models to investigate the roles of HETEs in different conditions.
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| http://dx.doi.org/10.1080/03602532.2023.2284110 | DOI Listing |
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