The profile of urinary lipid metabolites in cats.

Polyunsaturated fatty acids including arachidonic acid (AA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are converted to lipid mediators by oxidation. Unlike other mammals, cats cannot synthesize AA. Since their lipid metabolic features remain unknown, we qualitatively analyzed 118 types of urinary lipid metabolites in healthy neutered cats. Using LC-MS, we found 26 lipid metabolites in urines of all individuals. In detail, 20 AA-, 5 EPA- and 1 DHA-derived lipid mediators were detected. Focusing on oxidative pathway, 17 cyclooxygenase-metabolites and 5 metabolites produced by non-enzymatic pathway were detected. Of interest, few lipoxygenase- or cytochrome P450-metabolites were excreted. Thus, AA-derived cyclooxygenase-metabolites mainly composed the urinary lipid metabolites in cats.

A new approach to the synthesis of polyunsaturated deuterated isoprostanes: total synthesis of d4-5-epi-8,12-iso-iPF3alpha-VI and d4-8,12-iso-iPF3alpha-VI.

The total and stereospecific synthesis of d(4)-5-epi-8,12-iso-iPF(3alpha)-VI 55 and d(4)-8,12-iso-iPF(3alpha)-VI 64, EPA-derived all-syn-isoprostanes (iPs), has been accomplished. Because of issues related to volatility and yield with some of the primary deuterated synthons an improved synthesis is presented. These two deuterated analogs were used to discover and quantify the presence of the corresponding endogenous isoprostanes in human urine. These assays may serve as a valuable index of oxidative stress in population with omega-3 fatty acid enriched diets containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and may also be useful as an index of the severity of inflammatory diseases such as atherosclerosis and Alzheimer's disease.

Urinary excretion of diols derived from eicosapentaenoic acid during n-3 fatty acid ingestion by man.

Epoxides and fatty acid diols derived from arachidonate by the action of cytochrome P-450 appear in human urine and have biological activities. Dietary eicosapentaenoic acid gives rise to prostaglandins in vivo, but vascular effects of n-3 supplements do not all correlate with altered types or amounts of in vivo cyclooxygenase products. We investigated whether dietary eicosapentaenoic acid could also be metabolized by cytochrome P-450, by assessing the excretion of its vicinal diols. Utilizing gas chromatography/negative chemical ionization mass spectrometry, we have found that humans ingesting n-3 fatty acids excrete vicinal diols of eicosapentaenoic acid in substantial quantities.

Dietary docosahexaenoic acid is retroconverted in man to eicosapentaenoic acid, which can be quickly transformed to prostaglandin I3.

In a 24 h kinetic study docosahexaenoic acid (DCHA, C22:6n-3) or eicosapentaenoic acid (EPA, C20:5n-3) were given in a single dose to healthy male volunteers. PGI3-M, the main urinary metabolite of prostaglandin I3 was below the detection limit in the control periods, but was excreted already in the first 4 h after ingestion of DCHA or EPA and decreased thereafter. Excretion of PGI2-M did not change significantly. In a second dietary trial DCHA and EPA were given cross-over to 7 healthy male volunteers for 6 days. PGI3-M was formed after DCHA and EPA in amounts of 35 and 20% of PGI2-M and showed a considerable interindividual variation. The structure of PGI3-M was verified by independent biochemical synthesis. Our data indicate that dietary DCHA is retroconverted to EPA in man, which is quickly transformed--like dietary EPA itself--to prostaglandin I3. DCHA may therefore serve as a precursor fatty acid for EPA and its cyclooxygenated and lipoxygenated products.