Compensating lipid fluxes generated by the aminophospholipid translocase

Abstract

By a combined kinetic and thermodynamic model on the transbilayer dynamics and asymmetric distribution of lipids in the red blood cell, compensating lipid fluxes to the exoplasmic leaflet have been analysed, counterbalancing the active transport of aminophospholipids to the cytoplasmic monolayer by the aminophospholipid translocase. The compensating fluxes are assumed to be of passive nature generated by forces of lateral mechanical stress and of lipid concentration differences between the two monolayers. These forces are shown to be caused and maintained by the operation of the aminophospholipid translocase. Simulations reveal that a reduction of the compensating fluxes upon ATP-depletion can be attributed to the inhibition of the aminophospholipid translocase. Thus, a Mg²⁺- and ATP-dependence of the outward movement of phospholipid analogues in the plasma membrane of red blood cells can be expected independent of the existence and operation of an ATP-dependent ‘floppase’ activity.

Key Words:

• aminophospholipid translocase
• floppase
• compensating flux
• thermodynamic model
• mechanical stress