Practice question

Movement of intact phospholipid with polar headgroup across hydrophobic core has activation energy exceeding 60 kJ per mol, making spontaneous flip-flop negligible within hours to days, so cells require dedicated translocase catalysts. Flippases are P-type P4-ATPases, ten members in mammals, that adopt E1-E2 conformational cycle phosphorylating conserved aspartate to translocate fluorescent NBD-labeled aminophospholipids from exoplasmic to cytoplasmic leaflet against concentration gradient at expense of ATP, maintaining phosphatidylserine inside. Floppases belong to ABC transporter family also using ATP to export choline-containing lipids and cholesterol outward, important for bile secretion and surfactant release in lungs. Scramblases such as TMEM16F ANO6 and Xkr8 are calcium-activated, ATP-independent, bidirectional, collapsing asymmetry during platelet activation allowing phosphatidylserine to promote thrombin generation via tenase assembly, and during apoptosis to flag dead cells for phagocytosis. Phospholipase A2 cleaves acyl chain generating lysophospholipid and arachidonate for prostaglandin synthesis, not translocating whole lipid. Genetic loss of ATP11C causes hemolytic anemia and B-cell lymphopenia illustrating physiological importance.