ABSTRACT
C-20 Trideuterated leukotriene A4 methyl ester was prepared by Wittig condensation of a deuterated C9-phosphonium salt with a C11-epoxydienal. It was then treated separately with glutathione, cysteinylglycine and cysteine. The resulting esters were saponified to give C-20 trideuterated leukotrienes C4, D4 and E4 respectively. Fast atom bombardment mass spectrometry showed that the synthetic compounds contained from 0.5 to 1.0% protium impurity. Introduction of deuterium at C-20 ensures that it is stable to a wide variety of reagents and reaction conditions. The deuterated leukotrienes will serve as internal standards for the quantitative analysis by mass spectrometry of endogenous sulfidopeptide leukotrienes present in biological fluids.
Subject(s)
Deuterium , Isotope Labeling , Leukotriene A4/analogs & derivatives , Leukotrienes/analysis , Leukotriene E4 , Mass Spectrometry/methods , SRS-A/analogs & derivatives , SRS-A/analysisABSTRACT
A number of prostaglandins and mono-hydroxylated fatty acids were investigated as substrates for NAD-dependent 15-prostaglandin dehydrogenase (15-PGDH) obtained from human HL-60 cells. Lipoxygenase and cyclooxygenase-derived substrates possessing an w-6 hydroxyl moiety (15-HETE, 13-HODD and HHT) were metabolized to corresponding keto derivatives at a rate comparable to that for prostaglandins E2 and F2 alpha. 12-HETE was a poor substrate and 5-HETE was not metabolized. The w-6 hydroxy fatty acids inhibited the metabolism of PGE2 and therefore they may play a role in modulating bioactive prostaglandin levels.
