Resolvin

[1][2] Resolvins belong to a class of polyunsaturated fatty acid (PUFA) metabolites termed specialized proresolving mediators (SPMs).

[3][4] Resolvins (Rvs) fall into several sub-classes based on the straight chain PUFA from which they are formed and derive their unique structure.

Certain isomers of RvDs are termed aspirin-triggered resolvin Ds (AT-RvDs) because their synthesis is initiated by a drug-modified COX-2 enzyme to form 17(R) hydroxyl rather than 17(S) hydroxyl residue of the RvEs; however, an unidentified as of 2023 cytochrome P450 enzyme(s) may also form this 17(R)-hydroxy intermediate and thereby contribute to the production of AT-RvEs.

These metabolites are formed by a wide range of cells and tissues by the initial metabolism of DHA to 7S-hydroperoxy-DHA and 4S-hydroperoxy-DHA by a 15-lipoxygenase (either ALOX15 or possibly ALOX15B) followed by the further metabolism of the two intermediates by ALOX5 to their 17-hydroperoxy derivatives; these di-hydroperoxy products are further altered to the cited RvDs by these oxygenases or by non-enzymatic reactions and the conversion of their peroxy residues ubiquitous cellular peroxidases.

COX-2 modified in activity by aspirin or atorvastatin or, alternatively, a microbial or possibly mammalian cytochrome P450 monoxygenase metabolizes EPA to its 18R-hydroperoxy derivative; this intermediate is then further metabolized by ALOX5 to a 5,6 epoxide which is hydrolyzed enzymatically or non-enzymatically to RvE1 and 18S-RvE1 or reduced to RvE2; alternatively the 18R-hydroperoxide is converted to the 17R,18S vicinal diol product, RvE3.