Esterified Oxylipins: Do They Matter?

Abstract

Oxylipins are oxygenated metabolites of fatty acids that share several similar biochemical characteristics and functions to fatty acids including transport and trafficking. Oxylipins are most commonly measured in the non-esterified form which can be found in plasma, free or bound to albumin. The non-esterified form, however, reflects only one of the possible pools of oxylipins and is by far the least abundant circulating form of oxylipins. Further, this fraction cannot reliably be extrapolated to the other, more abundant, esterified pool. In cells too, esterified oxylipins are the most abundant form, but are seldom measured and their potential roles in signaling are not well established. In this review, we examine the current literature on experimental oxylipin measurements to describe the lack in reporting the esterified oxylipin pool. We outline the metabolic and experimental importance of esterified oxylipins using well established roles of fatty acid trafficking in non-esterified fatty acids and in esterified form as components of circulating lipoproteins. Finally, we use mathematical modeling to simulate how exchange between cellular esterified and unesterified pools would affect intracellular signaling.. The explicit inclusion of esterified oxylipins along with the non-esterified pool has the potential to convey a more complete assessment of the metabolic consequences of oxylipin trafficking.

Factors affecting variability in free oxylipins in mammalian tissues

“…There are many more oxylipins likely to be discovered, as >500 unique signals that are consistent with known and likely free oxylipins were reported in human plasma [12]. In addition to free oxylipins, esterified oxylipins are an important pool of oxylipins, as recently discussed [13], but are not further addressed in the review herein. Several excellent earlier reviews of factors that contribute to free oxylipin variability in mammalian samples are available [14][15][16], so this review focusses on the evidence and insights pertaining to free oxylipin variability that have been published in the past 18 months.…”

Quantitative Profiling Method for Oxylipins in Neurodegenerative Diseases by Liquid Chromatography Coupled with Tandem Mass Spectrometry

“…To gain a comprehensive understanding of the function of PUFA metabolites, 34 we needed to analyze both free and esterified oxylipins because studies have revealed that several oxylipins also initiate their effects through their phospholipid-esterified product. 35 In addition, recent studies revealed that the cell membrane can act as a reservoir for free epoxy-FAs, and an external stimulus can trigger the release of these esterified epoxy-FAs, triggering subsequent biological effects. 36 To determine the total oxylipin levels, a well-established KOH/methanol method was used based on a published paper 37 (the detailed hydrolysis method is described in SI).…”

Stearidonic acid improves eicosapentaenoic acid status: studies in humans and cultured hepatocytes

“…Enzymatic routes for oxylipin synthesis are catalyzed by lipoxygenases (LOX), cyclooxygenases (COX), cytochrome P450 monooxygenases (CYP450) and soluble epoxid hydrolase (sEH) while resulting metabolites are mainly hydroxy-, epoxy-and dihydroxy-PUFAS (25,26). Oxylipins can be esterified with phospholipids in membranes or are non-esterified (27). Well known oxylipins such as prostaglandins, thromboxanes and leucotrienes are classical eicosanoids formed from C20 fatty acids (i.e., ARA) which exhibit a wide variety of biological activities (28,29).…”