Differential hepatic processing and biliary secretion of head-group and acyl chains of liposomal phosphatidylcholines.
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.
Verkade
H J
HJ
Department of Pediatrics, University of Groningen, The Netherlands.
Derksen
J T
JT
Gerding
A
A
Scherphof
G L
GL
Vonk
R J
RJ
Kuipers
F
F
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000378:metabolism*; D007700:Kinetics; D008081:Liposomes / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010713:Phosphatidylcholines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D008081:Liposomes; D010713:Phosphatidylcholines; D015060:1,2-Dipalmitoylphosphatidylcholine; C017251:1,2-oleoylphosphatidylcholine