Lefkowith J B, Flippo V, Sprecher H, Needleman P
J Biol Chem. 1985 Dec 15;260(29):15736-44.
The effects of essential fatty acid (EFA) deprivation on the arachidonate content and phospholipid composition of different tissues are quite diverse. When C57B1 mice were placed on a fat-free diet, hepatic liquids were readily depleted of arachidonate. In contrast, the renal cortex tenaciously retained arachidonate, whereas surprisingly the heart showed a doubling of its content of arachidonate. This increase in cardiac arachidonate was due to a four-fold increase in arachidonylphosphatidylethanolamine (PE). The renal cortex showed preservation of its arachidonate content in PE, phosphatidylserine, and phosphatidylcholine. Only phosphatidylinositol was depleted of arachidonate in heart or renal cortex. Using an in vivo labeling technique, it was shown that the liver incorporated most of the [1-14C]arachidonate initially following intraperitoneal injection. Over 11 days, as levels of labeled arachidonate fell in liver, the EFA-deficient heart accumulated arachidonate selectively in PE (8-fold greater than control), and the EFA-deficient renal cortex accumulated arachidonate in PE, phosphatidylserine, and phosphatidylcholine (2-3-fold greater than control). This uptake was shown to be specific for arachidonate over 20:3(n-9). Despite the conservation of cardiac and renal arachidonate seen with EFA deficiency, prostaglandin production by the isolated perfused EFA-deficient heart and kidney was markedly decreased relative to control in response to specific agonist stimulation with angiotensin II, although it was equivalent to control in response to nonspecific stimulation by ischemia. These data suggest that the liver serves to supply other tissues with arachidonate in EFA deficiency, and that the heart and renal cortex both contain mechanisms to accumulate arachidonate selectively in certain phospholipids. However, phosphatidylinositol, which is uniquely depleted of arachidonate in heart and renal cortex with EFA deficiency, appears to be the principal source of arachidonate in response to receptor-mediated agonists.
必需脂肪酸（EFA）缺乏对不同组织中花生四烯酸含量和磷脂组成的影响差异很大。当C57B1小鼠置于无脂肪饮食时，肝组织液中的花生四烯酸很容易耗尽。相比之下，肾皮质能顽强地保留花生四烯酸，而令人惊讶的是，心脏中的花生四烯酸含量却增加了一倍。心脏中花生四烯酸的这种增加是由于花生四烯酰磷脂酰乙醇胺（PE）增加了四倍。肾皮质中花生四烯酸在PE、磷脂酰丝氨酸和磷脂酰胆碱中得以保留。只有心脏或肾皮质中的磷脂酰肌醇耗尽了花生四烯酸。使用体内标记技术表明，腹腔注射后，肝脏最初摄取了大部分[1-14C]花生四烯酸。在11天的时间里，随着肝脏中标记花生四烯酸水平的下降，缺乏EFA的心脏在PE中选择性地积累了花生四烯酸（比对照组高8倍），而缺乏EFA的肾皮质在PE、磷脂酰丝氨酸和磷脂酰胆碱中积累了花生四烯酸（比对照组高2-3倍）。这种摄取被证明对花生四烯酸具有特异性，超过20:3(n-9)。尽管EFA缺乏时心脏和肾脏中的花生四烯酸得以保留，但与对照组相比，在血管紧张素II的特异性激动剂刺激下，离体灌注的缺乏EFA的心脏和肾脏产生的前列腺素明显减少，尽管在缺血的非特异性刺激下其与对照组相当。这些数据表明，在EFA缺乏时，肝脏为其他组织提供花生四烯酸，并且心脏和肾皮质都含有在某些磷脂中选择性积累花生四烯酸的机制。然而，在EFA缺乏时心脏和肾皮质中独特地耗尽花生四烯酸的磷脂酰肌醇，似乎是对受体介导的激动剂产生反应时花生四烯酸的主要来源。
