Substrate specificity of human plasma phospholipid transfer protein

Area of Science:

• Biochemistry
• Lipid Metabolism
• Protein-Lipid Interactions

Background:

• Phospholipid transfer proteins (PLTPs) play a vital role in lipoprotein metabolism and lipid transport.
• High-density lipoproteins (HDL) are key acceptors of phospholipids during this process.
• Understanding the factors influencing PLTP-mediated lipid transfer is essential for comprehending lipoprotein dynamics.

Purpose of the Study:

• To investigate the influence of vesicle composition and size on phospholipid transfer mediated by human plasma phospholipid transfer protein.
• To examine the effect of chemical modifications of high-density lipoproteins (HDL) on their ability to accept phospholipids.
• To elucidate the relationship between HDL apolipoprotein charge and phospholipid transfer activity.

Main Methods:

• Utilized L-alpha-[14C]dipalmitoylphosphatidylcholine (DPPC) for phospholipid transfer assays.
• Employed vesicles of varying compositions (cholesterol, sphingomyelin) and sizes.
• Assessed HDL apolipoprotein modifications using fluorescence measurements, SDS-PAGE, and gel chromatography.

Main Results:

• Phosphatidylcholine (PC) transfer was inhibited by cholesterol and sphingomyelin in vesicles, with effects correlated to membrane fluidity.
• Increased vesicle size and decreased bilayer curvature reduced PC transfer, with no transfer observed for the largest vesicles.
• HDL acceptor ability decreased with increased negative apolipoprotein charge without PLTP, but increased initially with PLTP before decreasing upon extensive modification.

Conclusions:

• Vesicle properties, including lipid composition and physical characteristics, significantly modulate phospholipid transfer by PLTP.
• HDL apolipoprotein charge plays a complex role in phospholipid acceptance, both with and without PLTP.
• These findings highlight the intricate regulation of lipid exchange in lipoprotein metabolism.