DESATURATION OF ESSENTIAL FATTY ACIDS USING STABLE ISOTOPE GC-MS

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Prolonged ethanol consumption has been found to lower the levels of polyunsaturated fatty acids especially, 20:4n6 and 22:6n3, in plasma lipoproteins, erythrocytes, livers, brains, and the retinas of primates and felines maintained on low EFA diets (in the central nervous system, 22:6n3 is the principal fatty acid which declined). This may be due to the inhibition of desaturation by ethanol and/or to an increase in lipid peroxidation products such as aldehydes (4-hydroxy-nonenal and 4-hydroxy- hexenal) and isoprostanes. The essential fatty acids (EFA), linoleate (18:2n6) and linolenate (18:3n3), are desaturated and elongated to arachidonate (20:4n6) and docosahexaenoate (22:6n3), respectively. A stable isotope gas chromatography-mass spectrometry (GC-MS) method is being used to examine the effects of ethanol on the production of poly- unsaturated fatty acids in vivo. Other GC-MS procedures are being used to investigate the production of 4-hydroxy-alkenals and the isoprostanes in tissues. Primates on a low EFA diet that have been consuming ethanol (11-15% of their calories) daily for three years have developed significant liver pathology. Along with moderate amounts of fat deposition and liver inflammation there are notable increases in the collagen levels both within the sinusoids and surrounding venal regions. The levels of the 4-hydroxy-alkenals and the isoprostanes were also elevated in the liver of animals consuming alcohol. The levels of 20:4n6 and 22:6n3 decreased in plasma lipoproteins, erythrocytes, and liver phospholipids. In the brains there were dramatically lower levels of 22:6n3 and higher levels of 22:5n6. In vivo EFA metabolism studies indicated that the uptake of 18:3n3 or 18:2n6 into the plasma was about the same in animals consuming alcohol as the controls. Primates consuming alcohol had increased a- and b-wave latencies and lower b-wave amplitudes in their electroretinograms compared to controls.