| Summary: | The hydrolysis of HDL phospholipids (PL) and glycerides by hepatic lipase (HL) has been investigated in native and reconstituted HDL particles (Lp2A-I). Fasting, normolipidemic HDL exhibit total lipid hydrolytic rates of between 10 and 36 nM FA/h per microM PL. Of the total fatty acids liberated with HDL3 only 1﹪; are from triolein (TG), while 49﹪ are from diolein (DG) and 50﹪; are from PL. A spherical reconstituted particle containing 2 molecules of apoA-I, 120 molecules of PL, and 20 molecules of TG exhibits a total lipid hydrolytic rate of 18 nM FA/h per microM PL and 93﹪; of the fatty acids liberated are from PL. Inclusion of 40 molecules of TG into the Lp2A-I particle doubles the rate of fatty acid hydrolysis by HL through a stimulation of TG hydrolysis. Further addition of 10 molecules of DG to the Lp2A-I complex has no effect on the overall rates of hydrolysis, but changes the substrate specificity, wherein 61﹪; of the fatty acids are from DG and both TG and PL hydrolytic rates are significantly reduced. Increasing the amount of DG in the Lp2A-I particle further stimulates total lipid hydrolysis by raising DG hydrolytic rates at the expense of PL and TG hydrolysis. A particle containing 10 molecules of TG and 40 molecules DG yields the fastest lipid hydrolytic rate of 143 nM FA/h per microM PL, which constitutes 96﹪; DG hydrolysis, 3﹪; TG hydrolysis, and 1﹪; PC hydrolysis. These data indicate that hepatic lipase acts primarily as a surface lipid lipase with HDL particles. DG is the preferred substrate of HL in HDL and the HDL-DG content regulates the hydrolysis of both PL and TG by HL.
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