Jn. Haselden et al., The metabolism of 3-phenoxybenzoic acid-containing xenobiotic triacylglycerols in vitro by pancreatic, hormone sensitive and lipoprotein lipases, BIOCH PHARM, 56(12), 1998, pp. 1591-1598
Two model substrates, rac-1-(3 -phenoxy-[ring- C-14]benzoyl)-2,3-dipalmitoy
l glycerol (1(3PBA)DPG) and sn-2-(3-phenoxy-[ring-C- 14]benzoyl)-1,3-dipalm
itoyl glycerol (2(3PBA)DPG), were compared with tri[1-C-14]palmitoylglycero
l or tri[9,10(n)-H-3]oleoylglycerol as substrates for pancreatic lipase, li
poprotein lipase, and hormone-sensitive lipase. The loss of 3PBA from the s
n-2 position was always low because of the positional specificity of the li
pases. The loss of 3PBA from the rac-1 position was similarly low with horm
one-sensitive ligase (about 7% of the loss of oleate), but higher with panc
reatic 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 C-1
4-3PBA was still in the form of a diacylglycerol after incubation with a li
pase, whereas free acid or monoacylglycerol forms would have been expected.
Lipoprotein lipase acting on 1-(C-14-3PBA)DPG produced nearly 70% of its p
roduct as nonesterified 3PBA and only 25% as the diacylglycerol. The result
s suggest that 3PBA-containing xenobiotic triacylglycerols, and the 3PBA-gl
ycerol ester bond in particular, are poorer substrates for lipases than are
their natural counterparts, with the result that high proportions of parti
ally digested xenobiotic acylglycerols are produced. The three lipases perf
ormed differently with the xenobiotic substrates; this could have consequen
ces for the relative rates of storage and clearance of the xenobiotic triac
ylglycerols from the body. BIOCHEM PHARMACOL 56;12:1591-1598, 1998. (C) 199
8 Elsevier Science Inc.