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，人们对人类知之甚少 体内必需脂肪酸的代谢。我们的研究重点是 婴儿在出生第一周以及以后的代谢能力 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的转化 不同胎龄婴儿的二十二碳六烯酸。这 有点令人惊讶的结果是，基本上每个婴儿都 能够在体内进行 n-3 和 n-6 脂肪酸相互转化。 此外，胎龄与胎龄呈反比关系。 特别是 DHA 的血浆氘富集。最少的 发育成熟的婴儿在这方面具有最大的代谢能力 尊重。这与大脑的突增生长是一致的 人类胎儿在妊娠的最后三个月。体型较小的婴儿 孕龄的代谢能力有所下降 脂肪酸，但大部分差异可以解释为 仅孕龄。在我们的成人工作中，普通志愿者、吸烟者 研究了吸烟者和酗酒者的必需脂肪酸 体内相互转化。控制饮食研究表明 增加饮食中的长链 n-3 脂肪酸会导致 在体内氘化脂肪酸最终产物的积累中 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并且 相对于正常情况，氘代 AA 和 DHA 含量更高 不吸烟者。吸烟者的酒精摄入量显着增加 等离子体中长链多不饱和化合物的氘富集， 特别是DHA。对于患有肝纤维化的酗酒者，氘 肝活检样本中 DHA 的富集度也有所增加 相对于没有肝脏组织病理学发现的酗酒者。这些 结果很重要，因为它们不支持共同持有的观点 该领域的概念是酒精抑制延伸/去饱和 必需脂肪酸。事实上，酒精刺激的假设 这条途径将与我们的结果更加一致。我们的 假设酒精会导致长链的分解代谢 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 DHA 的组织浓度。代谢过程包括 延伸/去饱和和运输/酰化可能会增加 酗酒者部分补偿了这些重要的损失 膜成分。