Phospholipid Scramblase - Enzyme Activation

Enzyme Activation

The enzymatic activity of scramblase depends on the calcium concentration present inside the cell. The calcium concentration inside cells is, under normal conditions, very low; therefore, scramblase has a low activity under resting conditions. Phospholipid redistribution is triggered by increased cytosolic calcium and seems to be scramblase-dependent, resulting in a symmetric distribution of negatively charged phospholipids between both leaflets of the lipid bilayer. All scramblases contain an EF hand-like Ca2+binding domain that is probably responsible for the calcium activation of the enzyme. The activity of scramblase does not require energy, meaning that there is no contribution of adenosine triphosphate in the process.

Scramblases are cysteine-rich proteins, possessing many cysteinyl sulfhydryl groups that are prone to modifications. Oxidation, nitrosylation, and blockage of these sulfhydril groups produce an enhanced scramblase activity. Patients with sickle cell disease exhibit a fraction of erythrocytes with an aberrantly enhanced exposure of phosphotidyl serine on their surface. As the erythrocytes of these patients have an enhanced oxidative stress, it is probable that increased scramblase activity might play a role in the etiology of the disease. Furthermore, it is well recognized that both reactive oxygen species and intracellular Ca2+ fluxes affect mitochondria at the beginning of the apoptotic program. Sulfhydryl modification of PLSCR3 in mitochondria during apoptosis may be a key regulator initiating the intrinsic apoptotic pathways.