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方法学，人们对人类知之甚少 体内必需脂肪酸代谢。我们的研究主要集中在 婴儿出生后第一周及以后的代谢能力 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以及亚麻酸酯的转化 在不同胎龄的婴儿中使用二十二碳六烯酸。这个 有些令人惊讶的结果是，基本上每个婴儿都是 能够在体内进行n-3和n-6脂肪酸的相互转化。 此外，胎龄与体重呈负相关。 尤其是血浆中的氚富集度更高。最少的 发育成熟的婴儿在这方面的代谢能力最强 尊重。这与发生在脑部的快速生长相一致 最后三个月的人类胎儿。对孩子来说很小的婴儿 妊娠期的新陈代谢能力有所减弱 脂肪酸，但大部分的差异可以用 仅限胎龄。在我们的成人工作中，正常的志愿者，吸烟者 研究人员对酗酒吸烟者的必需脂肪酸进行了研究 体内的相互转换。控制饮食的研究表明 增加饮食中的长链n-3脂肪酸会导致减少 氢化脂肪酸终末产物在体内的积累 血浆。这与众所周知的End现象是一致的 产物抑制。吸烟者产生的量增加，并 与正常相比，氢化AA和DHA的丰度更高 非吸烟者。酗酒的吸烟者有明显的增加 长链多不饱和物在血浆中的氢浓缩， 尤其是DHA。在酒精性肝纤维化患者中，氚 肝活检样本中DHA的丰度也有所增加。 相对于没有肝脏组织病理学发现的酗酒者。这些 结果意义重大，因为它们不支持普遍持有的 该领域的观点认为酒精能抑制伸长/降低饱和度 必需脂肪酸。事实上，一种假设认为酒精会刺激 这条路径将与我们的结果更一致。我们的 假设酒精会导致长链的分解代谢 像DHA一样的多不饱和物。当酒精挑战是 足够的强度和持续时间，这将导致 组织中DHA的浓度。代谢过程包括 延长/去饱和度和转运/酰化可能增加 酗酒者在部分赔偿这些重要的损失 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.