ACYL-CHAIN AND HEADGROUP SPECIFICITY OF HUMAN PLASMA PHOSPHOLIPID TRANSFER PROTEIN

Phospholipid transfer protein (PLTP) is a plasma protein with two repo rted in vitro activities: transfer of phospholipids and modulation of HDL particle size. The mechanism of PLTP-mediated phospholipid transfe r was studied by determining the acyl chain and headgroup specificity and comparing the results with those obtained with the non-specific li pid transfer protein (ns-LTP), a previously characterised intracellula r transfer protein. To verify the results obtained with purified plasm a PLTP, recombinant PLTP produced in COS-1 cells was used. The transfe r rates were determined by monitoring the transfer of fluorescent, pyr ene-labeled phospholipids from quenched donor phospholipid vesicles to HDL, particles. When the length of the pyrene-labeled acyl chain was varied from 6 to 14 carbons, a fairly monotonous decrease in the trans fer rate was observed. No difference in rate was observed for the isom ers having the pyrene-labeled and unlabeled acyl chains in reversed po sitions, PLTP mediated equally the transfer of the various headgroup d erivatives except phosphatidylethanolamine (PE), which was transferred 2-3-fold more slowly. In all experiments the plasma and recombinant P LTP behaved identically. The specificity patterns observed for PLTP an d ns-LTP were very similar. No PLTP-phospholipid intermediate could be observed, indicating that PLTP, like ns-LTP, does not form a tight co mplex with the lipid substrate and may thus mediate the transfer of ph ospholipid via another, yet unspecified mechanism.