Differential hepatic processing and biliary secretion of head-group and acyl chains of liposomal phosphatidylcholines.
Differential hepatic processing and biliary secretion of head-group and acyl chains of liposomal phosphatidylcholines.
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脂质体磷脂酰胆碱的头基和酰基链的差异肝脏处理和胆汁分泌。
DOI：
10.1042/bj2750139
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
F. Kuipers
中科院分区：
文献类型：
--
作者：
H. Verkade;J. Derksen;A. Gerding;G. Scherphof;R. Vonk;F. Kuipers
为了研究血浆来源的磷脂酰胆碱 (PC) 对胆汁 PC 的贡献，在大鼠中研究了脂质体相关 PC 的肝脏加工和胆汁分泌。为此，小单层囊泡（SUV），含有微量的[2-棕榈酰-9,10-3H]二棕榈酰磷脂酰胆碱（[棕榈酰-3H]DPPC），[胆碱-14C]-二棕榈酰磷脂酰胆碱（[胆碱-14C]DPPC），二[14C]棕榈酰磷脂酰胆碱（[14C]DPPC）或二[1-14C]-油酰磷脂酰胆碱（[14C]DOPC）静脉内给予未麻醉的大鼠，这些大鼠在心脏和胆管中配备有永久性导管。 DPPC 的 14C 头基标记的胆汁分泌非常缓慢（4 小时内注射剂量的 0.3%），而 [3H] 棕榈酰标记的分泌速度要高得多（4 小时内 16%），但只有在酰基链大量分解代谢后才分泌。为了更详细地研究后一个过程，我们比较了[1-14C]酰基标记的DPPC和DOPC的肝脏代谢和胆汁分泌。在经过 8 天胆汁引流的大鼠中，油酰链的降解产物用于合成胆汁酸，随后分泌到胆汁中（6 小时内为 2%）。一小部分（6 小时内为 0.6%）以 PC 和溶血 PC 的形式分泌。当SUV注射后立即开始胆汁引流时，即肝脏胆汁酸合成率低且磷脂分泌高的情况下，胆汁酸形式的[14C]DOPC衍生放射性的分泌减少（6小时内0.2%），而（lyso-）PC则增加（6小时内1.5%）。胆汁转移大鼠中 DPPC 棕榈酰链的胆汁分泌远少于油酰链，并且主要以 PC 和溶血 PC 形式出现（0.6%，而 6 小时内以胆汁酸形式分泌 0.4%）。呼吸分析表明，两条酰基链的相当一部分被氧化为 CO2 并过期：在 4 小时内，油酰基链和棕榈酰基链分别占给药标签的 25.1% 和 13.4%。这项研究的结果表明，脂质体 PC 仅通过直接途径最低限度地分泌到胆汁中；大部分在肝脏中被广泛降解。所得产物部分以胆汁酸或再合成 PC 的形式分泌到胆汁中。油酰基和棕榈酰基酰基链的代谢似乎存在数量差异。
To investigate the contribution of plasma-derived phosphatidylcholine (PC) to bile PC, the hepatic processing and biliary secretion of liposome-associated PC was studied in rats. For this purpose, small unilamellar vesicles (SUV), containing trace amounts of [2-palmitoyl-9,10-3H]dipalmitoylphosphatidylcholine ([palmitoyl-3H]DPPC), [choline-14C]-dipalmitoylphosphatidylcholine ([choline-14C]DPPC), di[14C]palmitoylphosphatidylcholine ([14C]DPPC) or di[1-14C]-oleoylphosphatidylcholine ([14C]DOPC), were administered intravenously to unanaesthetized rats, equipped with permanent catheters in heart and bile duct. Biliary secretion of the 14C-head-group label of DPPC was very slow (0.3% of injected dose in 4 h), whereas the [3H]palmitoyl label was secreted at a much higher rate (16% in 4 h), but only after substantial catabolism of the acyl chain. To study the latter process in more detail, we compared hepatic metabolism and biliary secretion of [1-14C]acyl-labelled DPPC and DOPC. In rats with an 8-day bile drainage, degradation products of the oleoyl chain were utilized for synthesis of bile acids, which were subsequently secreted into the bile (2% in 6 h). A much smaller fraction (0.6% in 6 h) was secreted as PC and lyso-PC. When bile drainage was started immediately after SUV injection, i.e. a situation with a low hepatic bile acid synthesis rate and a high phospholipid secretion, the secretion of [14C]DOPC-derived radioactivity in the form of bile acids was decreased (0.2% in 6 h), and that as (lyso-)PC increased (1.5% in 6 h). Biliary secretion of DPPC palmitoyl chains in bile-diverted rats was much less than that of the oleoyl chains, and occurred predominantly as PC and lyso-PC (0.6%, compared with 0.4% as bile acids in 6 h). Breath analyses demonstrated that a considerable fraction of both acyl chains was oxidized to CO2 and expired: 25.1% of the administered label for oleoyl chains and 13.4% for palmitoyl chains respectively in a 4 h period. The results of this study indicate that liposomal PC is only minimally secreted into bile via a direct pathway; the bulk is extensively degraded in the liver. Resulting products are partly secreted into bile, as bile acid or as resynthesized PC. There appears to be a quantitative difference in the metabolism of oleoyl and palmitoyl acyl chains.