Scramblase

Scramblase is a hypothetical protein thought to be responsible for transportation of phospholipids between the two monolayers of a lipid bilayer of a cell membrane^[1]. Scramblase is a special member of the general family of transmembrane lipid transporters known as flippases. The inner-leaflet facing the inside of the cell contains negatively-charged amino-phospholipids and phosphatidylethanolamine. The outer-leaflet, facing the outside environment, contains phosphatidylcholine and sphingomyelin. Scramblase is an enzyme, present in the cell membrane, which transports (scrambles) the negatively-charged phospholipids from the inner-leaflet to the outer-leaflet, and vice versa.

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Biochemical properties

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. An increase in calcium concentration activates the phospholipid transportation activity, resulting in a symmetric distribution of negatively-charged phospholipids between both leaflets of the lipid bilayer. The transportation activity of scramblase does not require energy, meaning that there is no contribution of adenosine triphosphate in the process.

Enzyme activation

Scramblase is inactive in healthy cells; however, activation occurs when cells are exposed to a variety of stress conditions.

Scramblase activity in platelets

Collagen is a protein found in the connective tissue, which is, in general, not in contact with flowing blood. Contact between collagen and flowing blood occurs when blood vessels are damaged by, for example, physical insults. The exposure of collagen to flowing blood starts a series of processes that end in the formation of a blood clot:

1. Adhesion of circulating blood platelets to collagen
2. Activation of dormant platelets via protein receptors that interact with the exposed collagen.
3. Several biochemical and morphological processes that are started by activated platelets.

Activation of platelets lead, for example, to a change in morphology, to the membrane expression of P-selectin, and to the activation of scramblase. (consult for further information the article about platelets)

Activation of scramblase causes the transport of negatively-charged phospholipids to the platelet membrane surface. The negatively-charged phospholipids form a catalytic surface for several inactive coagulation factors present in blood such as prothrombin, factor Va, and factor Xa. (consult for further information the article about the prothrombinase complex)

Scramblase activity during apoptosis

Scramblase is also thought to be involved in the transportation of negatively-charged phospholipids to the cell membrane surface of cells that have become apoptotic. Apoptosis is a cellular process that occurs under stress conditions such as exposure to ultra-violet radiation (in sun rays) or toxic chemicals. The negatively-charged phospholipids on the cell surface function as a recognition marker for white blood cells. The white blood cells respond to this marker by phagocytosis of the apoptotic cell.