The relative rate of biosynthesis of dolichol from [3H]mevalonate in nine rat organs was studied in slices and in the whole animal. This biosynthesis was also compared to that of cholesterol and ubiquinone. All tissues examined are able to synthesize dolichol, as well as ubiquinone and cholesterol. Comparison of the data from slices in vitro with the in vivo studies demonstrated relatively good agreement for dolichol and ubiquinone synthesis. Although dolichol of high specific radioactivity was recovered in the blood, redistribution between organs, such as occurs with cholesterol, appears to be insignificant. The highest rates of dolichol biosynthesis were found in kidney, spleen and liver. On the other hand, muscle makes the largest contribution to total body dolichol synthesis. Newly synthesized dolichol also appears in the bile, but excretion by this route is far from sufficient to account for dolichol turnover.Incorporation of mevalonate into the final products is mainly dependent on biosynthetic activity. For comparison of the biosynthetic rates in different organs, possible sources of errors (such as variations in the size of the precursor pool, limitation by the rate of precursor uptake or non-linear incorporation) were investigated and corrected for. An isotope-dilution technique was developed and used to demonstrate a sixfold variation in the size of the mevalonate pool in various organs. Equilibration of this pool with exogenous mevalonate is a rapid and passive process. The size of the mevalonate pool does not determine the rates of cholesterol and dolichol biosynthesis, indicating the presence of regulatory steps in the terminal portion of these biosynthetic pathways.Dolichol and its derivatives are widely distributed in experimental systems and in human tissues, being present in all tissues and organelles [l, 21. While the phosphorylated form has an established role in the biosynthesis of N-glycosidically linked oligosaccharide moieties of glycoproteins, the function(s) of the free alcohol and its esterified form is much less clear. It has been demonstrated, however, that the presence of these lipids in model membranes influences membrane stability, fluidity and permeability to a considerable extentIn the initial steps of biosynthesis cholesterol, ubiquinone and dolichol follow a common pathway involving mevalonate [5]. The branching point is farnesyl-PP, after which one pathway leads to cholesterol, trans-trans addition of isopentenyl-PP gives rise to ubiquinone and cis-cis addition yields a series of dolichols. The main rate-limiting step in cholesterol synthesis is at the level of hydroxymethylglutarylCoA reductase and the activity of this enzyme is extensively regulated by a number of structural, metabolic and hormonal factors.Synthesis of dolichol and dolichyll-P has been demonstrated in the liver [6-91, thyroid Enzyme. 3-Hydroxy-3-methylglutaryl-coenzyme-A reductase (EC 1.1.1.34). mammals in vivo, with sliced, minced or disrupted tissues, isolated and cultured cells or subcellular organelles...
In about 50% of classical Hodgkin lymphomas, the Hodgkin/Reed Sternberg (H/RS) cells carry Epstein-Barr virus (EBV).
An effective system for perfusing rat liver using complete tissue culture medium and washed calf erythrocytes as oxygen carriers was devised. Infusion of taurocholate and glucose proved necessary to maintain stable metabolic activity and bile secretion during a 6-hr period. Perfusate pO2, pCO2 and pH values were monitored continuously and found to be stable. Electron microscopic examination revealed the maintenance of normal hepatic structure, even after 6 hr. Normal rates of protein and urea synthesis, no leakage of cytoplasmic enzymes, and continuous bile acid production demonstrated the functional integrity of this system. Using [3H]mevalonic acid as precursor, dolichol, dolichyl phosphate, ubiquinone and cholesterol were found to be continuously synthesized in this perfused liver system. All these lipids appeared in the perfusate, indicating discharge through the ER-Golgi system. The lipoproteins of the perfusate were isolated by ultracentrifugation and characterized with respect to size distribution and lipid composition. Dolichol was found in VLDL, LDL and HDL fractions, with the highest concentration present in the latter. In rat and human blood plasma this lipid was mainly associated with HDL. The ubiquinone in the perfusate was primarily associated with the VLDL fraction, while in rat plasma it was found more evenly distributed among all the three lipoprotein fractions studied. Dolichol, ubiquinone and cholesterol were also discharged to the bile, whereas dolichyl phosphate was not. Thus, newly-synthesized dolichol and ubiquinone are transported out of the hepatocyte to the blood and to the bile.
Merkel cell carcinoma (MCC) of the skin is a rare, primary malignant skin neoplasm which can present as a cutaneous nodule. These neoplasms are seen primarily in the elderly and located in the head and neck area or extremities. Twenty‐nine aspirates from primary and metastatic lesions obtained by percutaneous fine‐needle aspiration in 19 patients have been studied. The cytomorphologic features, clinical information, and immunocytochemical (ICC) findings are detailed. Aspirate smears demonstrated small‐to‐intermediate‐sized cells with a loosely cohesive pattern. Nuclei were round with finely granular chromatin and multiple, small nucleoli. Cells possessed a thin rim of cytoplasm, and infrequent pseudorosette formations were noted in cell groups. ICC results were universally positive for cytokeratin, which showed a paranuclear “dot‐like” pattern. Neuron‐specific enolase, epithelial membrane antigen, and S‐100 protein were positive in varying degrees. Leukocyte common antigen was universally negative. The diagnosis of MCC of the skin by FNA can be made by applying cytologic features in addition to ancillary studies and clinical information. Diagn. Cytopathol. 1998;18:251–257. © 1998 Wiley‐Liss, Inc.
Conditions for the isolation and quantitation of dolichyl phosphate, dolichol, cholesterol, and ubiquinone by reversed phase high performance liquid chromatography were investigated. A simple and fast sample preparation procedure using prepacked mini columns was employed. The UV spectra of the fractions obtained were examined and, in the case of dolichol compounds, the maximum absorbance around 205 nm was shown to be linearly dependent on the number of double bonds present in the isoprenolog. The analytical procedure described shows a very broad range of linearity (five orders of magnitude) and detects single dolichyl phosphate isoprenologs in amounts as small as 0.1 ng. The lowest overall recovery, that for dolichyl phosphate, is 77%. Use of isoprenolog 23 and ergosterol as internal standards reduced the variation in the method to 2.5, 4.0 and 5.5% for cholesterol, dolichyl phosphate and dolichol, respectively. The method described was employed to study the lipid composition of rat organs and biological variations in these compositions.
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