DESATURATION OF ESSENTIAL FATTY ACIDS USING STABLE ISOTOPE GC-MS

在最近稳定同位素的应用之前 基于GC/MS方法，对人类的了解很少 体内必需脂肪酸代谢。我们的研究集中在 婴儿在出生后第一周的代谢能力， 人类成年人这项工作的第一阶段定义了转换 亚油酸转化为花生四烯酸， 在不同胎龄的婴儿中使用二十二碳六烯酸。的 有些令人惊讶的结果是，基本上每个婴儿 能够在体内进行n-3和n-6脂肪酸相互转化。 此外，胎龄与 尤其是DHA的血浆氘富集。最不 发育良好的婴儿在这方面的代谢能力最强， 尊重这与大脑发育突增是一致的， 人类胎儿的最后三个月婴儿小， 胎龄的婴儿的代谢能力有所下降， 脂肪酸，但大部分的差异可以解释与 仅孕龄。在我们的成人工作中，正常的志愿者，吸烟者 和酗酒者的必需脂肪酸 体内相互转化。控制饮食的研究表明， 增加饮食中的长链n-3脂肪酸导致 在氘代脂肪酸终产物的体内积累中， 等离子体这与众所周知的结束现象是一致的 产物抑制吸烟者产生的量增加， 氘代AA和DHA相对于正常的更高的富集 不吸烟的人。酗酒的吸烟者有显着增加， 血浆中长链多不饱和化合物的氘富集， 尤其是DHA。在患有肝纤维化的酗酒者中， 肝活检样品中DHA的富集也增加 与无肝组织病理学发现的酗酒者相比。这些 结果是显著的，因为它们不支持通常持有的 在本领域中的概念是酒精抑制蛋白质的伸长/去饱和， 必需脂肪酸事实上，一个假设是酒精刺激 这条路径会更符合我们的结果。我们 一种假说是酒精导致长链 多不饱和脂肪酸，如DHA。当酒精挑战是 足够的强度和持续时间，这将导致减少 DHA的组织浓度。代谢过程包括 延长/去饱和和运输/酰化可以增加， 酗酒者部分补偿了这些重要的损失 膜成分

Prior to the recent application of stable isotope based GC/MS methodology, little was known about human essential fatty acid metabolism in vivo. Our studies have focused on the metabolic capacity of infants in the first week of life and also on human adults. The first phase of this work defined the conversion of linoleic acid to arachidonate and also the conversion of linolenate to docosahexaenoate in infants of varying gestational ages. The somewhat surprising results were that essentially every infant was capable of both n-3 and n-6 fatty acid interconversions in vivo. Moreover, there was an inverse relationship of gestational age with plasma deuterium enrichment of DHA, in particular. The least developed infants had the greatest metabolic capability in this respect. This is consistent with the brain growth spurt that occurs in human fetuses during the last trimester. Infants who were small for gestational age had a somewhat diminished metabolic capacity for fatty acids but most of the variance could be explained with gestational age only. In our adult work, normal volunteers, smokers and alcoholic smokers were studied for essential fatty acid interconversions in vivo. Controlled diet studies indicated that increasing the long chain n-3 fatty acids in the diet led to a decrease in the in vivo accretion of the deuterated fatty acid end products in plasma. This is consistent with the well known phenomenon of end product inhibition. Smokers produced increased amounts and had greater enrichments of deuterated AA and DHA relative to normal non-smokers. Alcoholic smokers had a marked increase in deuterium enrichments of long chain polyunsaturates in plasma, particularly DHA. In alcoholics with liver fibrosis, deuterium enrichment of DHA in liver biopsy samples was also increased relative to alcoholics without liver histopathological findings. These results are significant as they do not support the commonly held notion in the field that alcohol inhibits elongation/desaturation of essential fatty acids. In fact, a hypothesis where alcohol stimulates this pathway would be more consistent with our results. Our hypothesis is that alcohol leads to catabolism of long chain polyunsaturates like DHA. When the alcohol challenge is of sufficient intensity and duration, this will lead to a decrease in the tissue concentration of DHA. Metabolic processes including elongation/desaturation and transport/acylation may be increased in the alcoholic in partial compensation for this loss of these important membrane constituents.