IN-VITRO PRODUCTION OF LONG-CHAIN PYRROLE FATTY ESTERS FROM CARBONYL-AMINE REACTIONS

The reaction of lipoxygenase pathway products methyl 9,10(Z)-epoxy-13- oxo-11(E)-octadecenoate (13-MZEO) and methyl 12,13(Z)-epoxy-9-oxo-10(E )-octadecenoate (9-MZEO), with butylamine and lysine was studied in or der to investigate whether some oxidized fatty acids are able to react with amino groups, analogously to volatile aldehydes, and, therefore, contribute to the overall protein damage produced during oxidative st ress. The reaction mixtures were incubated at room temperature or 37 d egrees C; the products were fractionated by semipreparative high perfo rmance liquid chromatography, and characterized by H-1 and C-13 nuclea r magnetic resonance spectroscopy and mass spectrometry. The products identified were methyl 9-hydroxy-9-(5-pentyl-N-alkylpyrrole-2-)nonanoa te and N-alkyl-2-pentylpyrrole for the 13-MZEO, and methyl 8-[5-(1'-hy droxyhexyl)-N-alkylpyrrole-2-]octanoate and methyl 8-(N-alkylpyrrole-2 -)octanoate for the 9-MZEO. Formation of these pairs of analogs sugges ted that compounds were produced by one mechanism with the loss of the 5-substituent as a short-chain aldehyde, which was identified for the 13-MZEO. A reaction mechanism that explains the formation of all thes e compounds is proposed and the biological significance of these findi ngs in relation to low density lipoprotein oxidation is discussed. Alt hough these results do not demonstrate the formation of long-chain pyr role fatty acids in vivo, they suggest that these pyrroles could be pr oduced as an ultimate step in the lipid peroxidation process.