Verkade H J, Derksen J T, Gerding A, Scherphof G L, Vonk R J, Kuipers F
Department of Pediatrics, University of Groningen, The Netherlands.
Biochem J. 1991 Apr 1;275 ( Pt 1)(Pt 1):139-44. doi: 10.1042/bj2750139.
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.
为研究血浆源性磷脂酰胆碱（PC）对胆汁PC的贡献，我们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，将含有微量[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）的小单层囊泡（SUV）静脉注射给未麻醉的大鼠，这些大鼠的心脏和胆管中装有永久性导管。DPPC的14C-头部基团标记的胆汁分泌非常缓慢（4小时内为注射剂量的0.3%），而[3H]棕榈酰标记的分泌速率要高得多（4小时内为16%），但这仅在酰基链大量分解代谢之后。为更详细地研究后一过程，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。在胆汁引流8天的大鼠中，油酰链的降解产物被用于合成胆汁酸，随后胆汁酸分泌到胆汁中（6小时内为2%）。以PC和溶血PC形式分泌的比例要小得多（6小时内为0.6%）。当在注射SUV后立即开始胆汁引流时，即肝脏胆汁酸合成速率低且磷脂分泌高的情况，[14C]DOPC衍生放射性以胆汁酸形式的分泌减少（6小时内为0.2%），而以（溶血）PC形式的分泌增加（6小时内为1.5%）。胆汁分流大鼠胆汁中DPPC棕榈酰链的分泌远少于油酰链，且主要以PC和溶血PC的形式分泌（0.6%，相比之下6小时内以胆汁酸形式分泌的为0.4%）。呼吸分析表明，相当一部分酰基链被氧化为CO2并呼出：在4小时内，油酰链的给药标记中有25.1%、棕榈酰链的给药标记中有13.4%被氧化。本研究结果表明，脂质体PC仅通过直接途径极少地分泌到胆汁中；大部分在肝脏中被广泛降解。产生的产物部分以胆汁酸或重新合成的PC的形式分泌到胆汁中。油酰和棕榈酰酰基链的代谢似乎存在定量差异。
