DESATURATION OF ESSENTIAL FATTY ACIDS USING STABLE ISOTOPE GC-MS

使用稳定同位素 GC-MS 使必需脂肪酸去饱和

• 批准号: 6097587
• 负责人: Norman Salem
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6097587
• 关键词: Macaca mulatta; alcoholic beverage consumption; alcoholic fatty liver; arachidonate; blood chemistry; blood lipoprotein; brain metabolism; cats; deuterium; dietary lipid; disease /disorder model; electroretinography; essential fatty acids; ethanol; fatty acid metabolism; gas chromatography mass spectrometry; linoleate; linolenate; lipid peroxides; liver metabolism; long chain fatty acid; nutrition related tag; retina; unsaturated fatty acids

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.

在最近应用稳定同位素之前 基于GC/MS方法，对人类知之甚少 体内必需的脂肪酸代谢。我们的研究重点是 婴儿第一周的代谢能力以及 人类成年人。这项工作的第一阶段定义了转换 亚油酸到蛛网酸，也是亚麻酸的转化 在不同的胎龄婴儿中进行纪录。这 令人惊讶的结果是，本质上每个婴儿都是 能够在体内进行N-3和N-6脂肪酸互转换。 而且，胎龄与 尤其是DHA的血浆氘富集。至少 发达的婴儿在这方面具有最大的代谢能力 尊重。这与发生在大脑生长中的一致 孕期人类胎儿。小的婴儿 胎龄的代谢能力有所降低 脂肪酸，但大多数方差可以用 仅胎龄。在我们的成人工作中，普通志愿者，吸烟者 并研究了酗酒者的必需脂肪酸 体内的互换。受控饮食研究表明 增加饮食中长链N-3脂肪酸导致降低 在体内积聚的氘化脂肪酸最终产物中 等离子体。这与众所周知的终点现象一致 产品抑制。吸烟者产生的数量增加，并 相对于正常的氘代AA和DHA的富集更大 非吸烟者。酗酒者显着增加 长链多不饱和的氘富集在血浆中， 特别是DHA。在肝纤维化的酒精中毒中 DHA在肝活检样品中的富集也增加了 相对于没有肝组织病理学发现的酗酒者。这些 结果很重要，因为它们不支持常见的 在现场的概念，酒精会抑制伸长/去饱和的 必需的脂肪酸。实际上，酒精刺激的假设 该途径将与我们的结果一致。我们的 假设是酒精会导致长链的分解代谢 像DHA一样多不饱和。当酒精挑战是 足够的强度和持续时间，这将导致降低 DHA的组织浓度。代谢过程包括 伸长/去饱和和传输/酰基化可能会增加 对这些重要的损失的部分补偿 膜成分。