The metabolism of 3-phenoxybenzoic acid-containing xenobiotic triacylglycerols in vitro by pancreatic, hormone-sensitive and lipoprotein lipases.
Two model substrates, rac-1-(3-phenoxy-[ring-14C]benzoyl)-2,3-dipalmitoyl glycerol (1(3PBA)DPG) and sn-2-(3-phenoxy-[ring-14C]benzoyl)-1,3-dipalmitoyl glycerol (2(3PBA)DPG), were compared with tri[1-14C]palmitoylglycerol or tri[9,10(n)-3H]oleoylglycerol as substrates for pancreatic lipase, lipoprotein lipase, and hormone-sensitive lipase. The loss of 3PBA from the sn-2 position was always low because of the positional specificity of the lipases. The loss of 3PBA from the rac-1 position was similarly low with hormone-sensitive lipase (about 7% of the loss of oleate), but higher with pancreatic lipase (about 35% that of oleate) and lipoprotein lipase (about 23% that of oleate). With one exception, more than 50% and up to 80% of the 14C-3PBA was still in the form of a diacylglycerol after incubation with a lipase, whereas free acid or monoacylglycerol forms would have been expected. Lipoprotein lipase acting on 1-(14C-3PBA)DPG produced nearly 70% of its product as nonesterified 3PBA and only 25% as the diacylglycerol. The results suggest that 3PBA-containing xenobiotic triacylglycerols, and the 3PBA-glycerol ester bond in particular, are poorer substrates for lipases than are their natural counterparts, with the result that high proportions of partially digested xenobiotic acylglycerols are produced. The three lipases performed differently with the xenobiotic substrates; this could have consequences for the relative rates of storage and clearance of the xenobiotic triacylglycerols from the body.
Haselden
J N
JN
Department of Biological Sciences, University of London, Wye College, Ashford, Kent, UK.
Hutson
D H
DH
Dodds
P F
PF
D000818:Animals; D001565:Benzoates / Q000378:metabolism*; D008049:Lipase / Q000378:metabolism*; D008071:Lipoprotein Lipase / Q000378:metabolism*; D010179:Pancreas / Q000201:enzymology; D051381:Rats; D014280:Triglycerides / Q000737:chemistry / Q000378:metabolism*; D015262:Xenobiotics / Q000378:metabolism*