Transverse asymmetry

Biological membranes are asymmetric structures. There are several kinds of asymmetry to consider. Both the lipids and the proteins of membranes exhibit lateral and transverse asymmetries. Lateral asymmetry arises when lipids or proteins of particular types cluster in the plane of the membrane. 

The respiratory chain contains components organized in a sided manner (transverse asymmetry) as required by the chemiosmotic theory. 

There is also inside-outside (transverse) asymmetry of the phospholipids. The choline-containing phospholipids (phosphatidylcholine and sphingomyelin) are located mainly in the outer molecular layer the aminophospholipids (phosphatidylserine and phos-phatidylethanolamine) are preferentially located in the inner leaflet. Obviously, if this asymmetry is to exist at all, there must be limited transverse mobility (flip-flop) of the membrane phospholipids. In fact, phospholipids in synthetic bilayers exhibit an extraordinarily slow rate of flip-flop the half-life of the asymmetry can be measured in several weeks. However, when certain membrane proteins such as the erythrocyte protein gly-cophorin are inserted artificially into synthetic bilayers, the frequency of phospholipid flip-flop may increase as much as 100-fold. 

Zachowski, A., 1993. PhosphoUpids in animal eukaryotic membranes transverse asymmetry and movement. Biochem. J., 294 1-14... 

The implication of the SM-CER signaling pathway in MTR opens intriguing avenues of research. Indeed, it has been suggested, for example, that apoptosis-resistant cells are deficient in SMase activation or SM hydrolysable pools (Santana et al., 1996 Bettai eb et al., 1996 Wright et al., 1996). In fact, we have shown in some resistant myeloid leukemia cells that the incapacity to generate CER in the presence of effector was in relation to a deficit of (hydrolysable) SM pool (Bettai eb et al., 1996). Thus, it is possible that, in some AML cells, the activation of a yet undefined SM translocase results not only in modification of SM transverse asymmetry but also in reduced SM hydrolysable pool, decreased CER production, and inhibition of apoptosis (Bezombes et al. 1998). Hence one can conclude from these studies that SMase activation is substrate dependent and therefore it is conceivable that spacial SM organisation is essential in the initiation of a SMase dependent apoptotic pathway. If this hypothesis were valid, one could concede that by modifying SM transverse distribution it would be possible to restore an apoptotic pathway in MTR cells. 

In experiments designed to explore whether there is protein transverse asymmetry in membranes, it was shown that when trypsin was used to treat intact erythrocytes, the carbohydrate groups of tiie transmembrane protein glycophorin were released from the N-terminus of this protein (as glycopeptides). This was taken as evidence that the N-terminus of glycophorin must be on the exterior side of the membrane because ... 

Several other techniques have been exploited to answer queries about asymmetrical compositions of plasma membranes. To make an observation of the transverse asymmetry in the distribution of certain membrane molecules requires that one side of the membrane be excluded from a reaction medium while a constituent is chemically altered, labeled or identified by its properties. Many such experiments have been conducted with intact erythrocytes which were reacted and then lysed and reacted again. The reactant saw initially only the outer surface of the membrane and eventually both sides. Qualitative or quantitative differences observed under these conditions allowed conclusions about the... 

CARRAWAY, 1975). The method has been most widely applied to the covalent labeling of free amino groups of plasma membrane constituents and therefore seems somewhat restrictive and nonspecific, Similarly, the iodination of proteins with 131i is not target specific but certainly it has yielded much insight about transverse asymmetry of membrane macromolecules. 

My discussion is concerned mainly with the transverse asymmetry in the distribution of plasma membrane enzymes. The scheme shown below indicates an inside-outside distribution pattern which is based on observations from several different laboratories. 

Serological studies have shown that the lipid distribution in the lamellar system of chloroplasts shows a lateral and transversal asymmetry (Radunz, 1980). We have analysed the lipid composition of chloroplasts from the variegated tobacco mutant Nicotiana tabacum NC 95. 

Transversal asymmetry of acyl lipids in the thylakoid membrane... 

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