Absorption study of fat-soluble vitamins into dipalmitoylphosphatidylcholine (DPPC) bilayer by MD simulations

Retinol, α-tocopherol and phylloquinone (vitamins A, E, and K) are presented in high concentrations within the chloroplast and leaves of most plants. They are fat-soluble vitamins and absorb similarly to other dietary lipids. Because the molecular mechanism of retinol, α-tocopherol, and phylloquinone absorption is still unknown, this work aims to investigate the distribution of these vitamins at the water/membrane interface using molecular dynamics (MD) simulations. Structures and variations of the hydroxyl group in vitamins are the keys to the investigation of the absorption process. Binding orientations, favorable binding sites, interactions, and diffusion of vitamins were identified. All vitamins spontaneously penetrate the lipid bilayer. According to simulations, the formation of the hydrogen bonding interaction with the phosphate group of DPPC during absorption requires a hydroxyl group of retinol and tocopherol. Therefore, retinol has -OH group at the tail of the structure and shows the highest structural flexibility of retinol, broadest tilt angle toward the lipid membrane, and highest diffusion coefficient. Finally, retinol plugs its head group into the hydrocarbon core of the lipid bilayer. In the case of α-tocopherol, the hydroxyl at the head group produces α-tocopherol, which moves through one leaflet of the lipid membrane and is stabilized in the opposite leaflet. Interestingly, phylloquinone, a molecule without a hydroxyl group, stabilizes close to a phosphate group without hydrogen bond formation. The head group of phylloquinone penetrates at a precise tilting angle of 120°. High retention of phylloquinone inside gel-phase DPPC is suggested by its low diffusion coefficient. MD simulations reveal the characteristics of three fat-soluble vitamins during absorption through the phospholipid membrane. This information is useful as a guideline to improve the absorption of drugs along the membrane.