Plasma membrane sterol derivatives

Isoprenoids represent the largest family of natural products, with an exceptional structural diversity. Isoprenoids are present in all living organisms. This group includes essential metabolites, such as sterols 27 (Fig. 6) of the eukaryotic plasma membranes, prenyl chains of the quinones 22 and 23 from electron transport chains, and carotenoids 25 from the photosynthetic apparatus in the plant chloroplasts, or in the phototrophic bacteria. Isoprenoids also include secondary metabolites of a more restricted distribution and with a less obvious physiologic significance. Their carbon skeleton can be derived from the combination of C5 subunits with the branched skeleton of isoprene. 

When multiplying, intracellular parasites do not synthesise their own membrane sterol, but must derive it from the host cell. It is interesting that the changes observed in erythrocytes infected with malaria merozoites are very similar to those brought about by depleting plasma membranes of cholesterol increased permeability, changes in Na and concentrations, increased acetylcholinesterase and adenylate cyclase activities [188-191]. 

Most authors find sterols of all forms to be particularly abundant in ER (Table V). It should be realized that in animal tissue the cellular membranes richest in cholesterol are the plasma and lysosomal membranes. Further fractionation of plant membranes may reveal a high content of sterol derivatives in plasma membrane, tonoplast, and other membranes. Duperonet al. (1975) measured the sterol content of cauliflower mitochondria and found that the inner membrane contained 28 pg sterol per milligram of protein and the outer membrane 77 p,g sterol per milligram of protein. This enrichment in the outer membrane is also found in animal mitochondria. 

Although much is known of the enzymatic steps in the biosynthesis of SE, SG, and ASG, much remains to be learned about the physiological importance of the reactions studied in vitro. The sites of biosynthesis of the sterol derivatives need to be studied at the same time as the accumulation of the compounds. Are sterol derivatives formed in the Golgi and then incorporated into the plasma membrane and tonoplast ... 

Therefore, if the recipient cell does not express the specific lipids required by the receptor (which may concern the acyl chain content of sphingolipids), or an adequate cholesterol-sphingolipid balance, the transfection experiment may lead to an abxmdant expression of a totally inactive receptor. In 2003, Opekarova and Tanner published a list of more than 30 membrane proteins whose activity is specifically affected by lipids. The list covered a broad range of proteins expressed by various bacteria, yeasts, insect, and mammalian cells. The problem is particularly acute when mammalian receptors or transporters are expressed in bacteria. For instance, the failure to express fxmctional serotonin transporters in E. coli has been attributed to the lack of cholesterol in bacteria. Moreover, the recovery of fully active neurotensin and adenosine receptors in transfected bacteria required the presence of choles-teryl hemisuccinate (a cholesterol derivative) during solubilization. Paradoxical results have also been obtained for some proteins whose activity requires cholesterol but can be fxmctionally expressed in bacterial hosts. In this case, one can exclude a direct interaction of cholesterol with the protein but rather consider a more general effect of the sterol on membrane properties. As a matter of fact, we are just at the beginning of our comprehension of the complex molecular ballet that involves bofh lipid and protein actors in the plasma membrane of excitable cells. 

Lipids are a complex group of substances, which include the long-chain fatty acids and their derivatives, sterols and steroids, carotenoids, and other related isoprenoids. It is evident that the term lipid denotes a wide range of compounds that appear to have little obvious interrelation. However, although these compounds possess widely different structures, they are derived in part from similar biological precursors and exhibit similar physical and chemical characteristics. Furthermore, most lipids occur naturally in close association with protein, either in membranes as insoluble lipid-protein complexes or as soluble lipoproteins of the plasma. 

Fig. 14. Diagranunatic representation of the pools and fluxes of cholesterol within the intestinal mucosal cell. Based upon the experimental data presented in this review, it is likely that at least 3 distinct subpools of cholesterol exist within the cell these include pool A, which is derived from sterol absorbed from the intestinal lumen (arrow 1) and serves principally as a substrate for acyl-CoA cholesterol acyhransferase (ACAT) (arrow 2) while that in pool B is supplied primarily by de novo synthesis from acetyl-CoA (arrow 4). pool C presumably receives a major contribution of sterol from pool B (arrow S) and a lesser contribution from pool A (arrow 3). The free sterol in this metabolically active pool is used for the synthesis of cell membranes (arrow 6) and for the surface coat of nascent chylomicrons (arrow 7). Triglycerides are also absorbed (arrow 8) and secreted in chylomicrons (arrow 9) into lymph. Finally, low-density lipoproteins (LDL) are taken up from the plasma and contribute to the metabolically active pool of cholesterol (arrow 10) (41J.

Dietary phytosterols have some influence on the biosynthesis of cholesterol in the body, although they are not used for making membranes and in the body they break down. To reduce the amount of cholesterol in blood plasma, the Recommended Daily Intake of phytosterols is about 250 mg. There are now margarines containing about 10% phytosterols (in the form of phytostanol esters derived from tall oil or in the form of sterol esters isolated from soybean oil). The importance of triterpene alcohols in the diet is not known. 

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