DHETs

DHETs, or dihydroxyeicosatrienoic acids, are a family of fatty acid metabolites derived from arachidonic acid, a 20-carbon polyunsaturated fatty acid. They are the diol products formed when the epoxide group of epoxyeicosatrienoic acids (EETs) is hydrolyzed by the enzyme soluble epoxide hydrolase (sEH). The four primary DHET regioisomers correspond to the four EETs: 5,6-DHET, 8,9-DHET, 11,12-DHET, and 14,15-DHET.

Formation and distribution: In tissues, cytochrome P450 epoxygenases convert arachidonic acid to EETs, which are biologically active signaling lipids with vasodilatory, anti-inflammatory, and pro-angiogenic effects. sEH then converts EETs to DHETs by adding a molecule of water across the epoxide, yielding vicinal diols. DHETs are found in plasma, urine, and tissues, and exist as several regioisomers, each with potentially different activity.

Biological roles: EETs are often more potent biologically than DHETs; DHETs generally have lower activity. The balance between EETs and DHETs, reflected by the EET/DHET ratio, is influenced by sEH activity. Pharmacological inhibition of sEH raises EET levels and lowers DHETs, an effect investigated for cardiovascular and metabolic diseases.

Clinical relevance and analysis: DHET levels serve as biomarkers of epoxygenase/sEH pathway activity. They are measured by liquid chromatography-tandem mass spectrometry in plasma or urine. Interpretation requires consideration of diet, genetics, and disease state, and artifactual formation during sample handling is a concern.