Practice question

Transverse asymmetry arises because lipid synthesis and active transport are polarized across bilayer and maintained continuously by energy-dependent enzymes. In ER, phosphatidylcholine is produced by CDP-choline pathway and partly enriches outer leaflet after vesicular trafficking, while phosphatidylserine synthesized by serine exchange enzymes PSS1 and PSS2 remains preferentially cytosolic. P4-ATPase flippases ATP11C and ATP8A1 hydrolyze ATP to move phosphatidylserine and phosphatidylethanolamine inward against gradient, while ABC floppases like ABCB4 and ABCC1 move phosphatidylcholine and cholesterol outward, and calcium-activated scramblases randomize quickly upon activation. Consequently phosphatidylcholine and sphingomyelin are about 60-75% outer, phosphatidylserine greater than 80% inner, phosphatidylethanolamine similarly inner, glycolipids exclusively outer. This selective asymmetry provides crucial functional cues: inner anionic phosphatidylserine binds polybasic motifs of K-Ras, protein kinase C, and synaptotagmin regulating membrane recruitment and exocytosis, while exposed phosphatidylserine signals engulfment or coagulation. Identical leaflet composition would erase electrochemical asymmetry, highlighting that asymmetry is actively maintained essential property for signaling, not random distribution.