-Alkynyl lipid surrogates for po XXXX free radical and enzymatic oxidations.

@entity844 @entity70776 @entity26 @entity1426 @entity1474 @entity9647 @entity505 @entity1718
Lipid and lipid metabolite profiling are important parameters in understanding the pathogenesis of many diseases. Alkynylated @entity1474 are potentially useful probes for tracking the fate of @entity844 metabolites. The nonenzymatic and enzymatic oxidations of   -alkynyl linoleic acid and   -alkynyl arachidonic acid were compared to that of linoleic and @entity1426 . There was no detectable difference in the primary products of nonenzymatic oxidation, which comprised cis,trans-hydroxy fatty acids. Similar hydroxy fatty acid products were formed when   -alkynyl linoleic acid and   -alkynyl arachidonic acid were reacted with lipoxygenase enzymes that introduce @entity26 at different positions in the @entity505 chains. The rates of oxidation of   -alkynylated fatty acids were reduced compared to those of the natural @entity1718 . @entity9647 did not oxidize alkynyl linoleic but efficiently oxidized alkynyl arachidonic acid. The products were identified as alkynyl 11-hydroxy-eicosatetraenoic acid, alkynyl 11-hydroxy-8,9-epoxy-eicosatrienoic acid, and alkynyl prostaglandins. This deviation from the metabolic profile of @entity1426 may limit the utility of alkynyl arachidonic acid in the tracking of cyclooxygenase-based lipid oxidation. The formation of alkynyl 11-hydroxy-8,9-epoxy-eicosatrienoic acid compared to alkynyl prostaglandins suggests that the   - @entity70776 group causes a conformational change in the @entity844 bound to the enzyme, which reduces the efficiency of cyclization of dioxalanyl intermediates to endoperoxide intermediates. Overall,   -alkynyl linoleic acid and   -alkynyl arachidonic acid appear to be metabolically competent surrogates for tracking the fate of @entity1474 when looking at models involving autoxidation and oxidation by lipoxygenases.
