Noncholesterol sterols.
Although most of us are more or less familiar with the term "cholesterol", the world of sterols is far more complicated and interesting. Apart from cholesterol, many non-cholesterol sterols can be found in human plasma and these sterols serve many important functions in human organism. They are either derived from endogenous biosynthesis of cholesterol or they come from dietary sources (phytosterols). The sole cholesterol molecule is used for keeping our cell membranes fit, for signalization purposes as well as a precursor for bile acids and steroid hormones. The compounds prior to cholesterol in its biosynthetic pathway were identified as vitamin D3 precursor, meiosis activating sterols and nowadays it seems that they could play a role in cholesterol homeostasis. The sterols from ingested vegetable sources, the phytosterols, are expelled from enterocytes and thus indirectly help our gut in coping with abundant cholesterol in the lumen. Higher plants synthesize many phytosterols, but in marine organisms, we can find other innumerous sterol molecules. The diversity of sterol molecules produced and resistance of their tetracyclic core to enzymatic activities implies crucial importance of sterols during the ontogenesis of multicellular organisms. First oxygen appeared on the Earth app. 2.7 billion years ago and since that time, every new life form took the advantage of oxygen needed also for build-up of sterol molecules. The last decades changed our view to the sterol molecules on almost at all levels of their appearance in human body. In the gut, the absorption of sterols was proven to be protein dependent and the quest for the transporter was successful. The general concepts of intracellular homeostasis of cholesterol have been described including the covalent interaction unbelievable so far - cholesterol and a protein. The clinical importance of non-cholesterol sterols rises with the effort to discover underlying facts about the causes of atherosclerosis. The compound in question, cholesterol, seems to be involved, but it sounds not to be crucial per se. The fact that the accumulation of phytosterols in sitosterolemia enhances the probability of early atherosclerosis onset further supports the hypothesis about some sterol (or steroid) compound being responsible on the molecular level for triggering the pathobiochemical cascade of events leading to atherosclerosis. Understanding the processes taking place in the enterocyte during the absorption of sterols resulted in synthesis of selective inhibitors at the level of sterol translocation into the enterocyte, sterol esterification and chylomicron packing, which are in different phases of clinical testing. The studies in the last part of the monograph represent the clinical potential of the analyses of non-cholesterol sterols. In well-defined groups, these analytes enables us to assess the changes in the homeostasis of cholesterol, which can be reflected in the concentration of total cholesterol. Furthermore, the high concentrations of some plasma sterols could point to the inborn errors of cholesterol biosynthesis (Smith-Laemli-Opitz syndrome), transport (sitosterolemia) or metabolization (cerebrotendinous xanthomatosis). Some issues concerning the research on the non-cholesterol sterols still remain unanswered - it is not known why some of the enzymes of the cholesterol biosynthesis (seladin-1, sterol D14 reductase) have other functions, qualitative aspects of sterol absorption are not satisfactorily explained and exact reason for expulsion of phytosterols from human body is not clear. Nevertheless, the authors hope that the presented facts can broaden the reader's perspective about the area, which is usually hidden beneath the cholesterol molecule.
Vecka
Marek
M
Charles University in Prague, First Faculty of Medicine, Clinical Department of Gastroenterology and Hepatology, Prague. marvec@volny.cz
Zak
Ales
A
Tvrzická
Eva
E
D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000235:genetics / Q000378:metabolism*; D009748:Nutrition Disorders / Q000235:genetics / Q000378:metabolism*; D010840:Phytosterols / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*
D010840:Phytosterols; D002784:Cholesterol