Comparison of acyl-oxyester and acyl-thioester lipids as substrates for bovine milk lipoprotein lipase.

The dithioester analog of dihexanoylphosphatidylcholine, rac-1,2-S,S-dihexanoyl-3-phosphocholine-1,2-dimercapto-3-propanol was synthesized and compared to the corresponding acyl-oxyester lipid as a substrate for bovine milk lipoprotein lipase. The apparent maximal reaction velocity (Vmax) for dihexanoyldithiophosphatidylcholine was considerably lower than that for dihexanoylphosphatidylcholine (0.12 vs. 5.0 mumol product released/min per mg lipoprotein lipase, respectively). The apparent Km values were 1.9 and 4.0 mM, respectively. 3-Butyrylthio-1,2-dibutyryloxypropane was also compared to tributyrylglycerol as a substrate for lipoprotein lipase; hydrolysis of the acyl-thioester bond was insignificant when compared to the corresponding oxyester derivative. Apolipoprotein C-II, the activator protein of lipoprotein lipase for long-chain fatty acyl substrates, had no effect on the hydrolysis of either the thio- or oxyester short-chain substrates. The low lipoprotein lipase activity for the thioester substrates is discussed in relation to the structure of the lipid and the active site of the enzyme.