Biomedical subjects
Publications and source records attributed to C Djerassi.
Fundamentally new approaches to birth control--for example, a male pill, a once-a-month menses inducer, and an antifertility vaccine--cannot be realized before the next century, and then only if the virtual withdrawal of the pharmaceutical industry from this field can be reversed. Major changes in product liability would be the most significant incentive.
The sponge Pseudaxinyssa sp., unique in sterol and fatty acid composition, was cellularly dissected into fractions enriched in each of the major cell types present in the sponge: microbial symbionts (cyanobacteria), small sponge cells (pinacocytes and choanocytes), and large sponge cells (archeocytes and cyanophytes). Three phototrophic microbial symbionts were also isolated from the cell fractions and grown in culture. An unsymmetrical distribution of fatty acids and sterols was observed for the sponge cells: small cells contained larger quantities of long chain fatty acids (greater than C24) and smaller quantities of sterols than were present in the larger sponge cells. Moreover, the rare sterols 24-isopropylcholesterol predominated in the smaller sponge cells, whereas its 22-dehydro analog predominated in the larger sponge cells. Long chain fatty acids and sterols were not detected in the cultured microbial symbionts. This constitutes the first report of lipid variability according to cell type for this most primitive group of Metazoa.
Analyses of fatty acids with carbon numbers between C12 and C22 are reported for five Great Barrier Reef sponges. These analyses indicate that phototrophic cyanobacterial symbionts (blue-green algae) present in three of the sponges are chemically distinct, whereas the other two sponges do not contain cyanobacterial symbionts. All the sponges contain other, nonphototrophic bacteria. The fatty acid analyses indicate that the non-phototrophic bacterial populations present in the different sponges are distinct in both their chemical compositions and their abundances. Nonphototrophic bacteria are estimated to account for between 60 and 350 micrograms/g (extractable fatty acids:tissue wet weight), whereas cyanobacteria account for between 10 and 910 micrograms/g. One sponge (Pseudaxinyssa sp.) contains a relatively large amount of the isoprenoid acid, 4, 8, 12-trimethyltridecanoic acid; this acid is presumed to be derived from phytol, a degradation product of chlorophyll. This sponge also contains relatively large amounts of the nonmethylene interrupted fatty acid, octadeca-5,9-dienoic acid. Analyses of interior and cyanobacteria-rich surface tissues of this sponge indicate that these two acids are probably not associated with the symbiotic cyanobacteria.
The first direct evidence is provided for the presence of unconventional lipids in a particular subcellular membrane system of a sponge. Spherulous cells were isolated from the variety of cell types present in the marine sponge Aplysina fistularis by density gradient centrifugation. Spherulous cell plasma membrane was subsequently isolated by cell rupture followed by differential centrifugation and sucrose, or Percoll, density gradient ultracentrifugation. Plasma membrane isolates were identified and assessed for purity using [3H]concanavalin A plasma membrane marker, sodium dodecyl sulfate polyacrylamide gel electrophoresis and ratios of protein, sterol and phosphate. Plasma membrane isolates could not be assessed for purity by traditional enzymatic means. Spherulous cell plasma membrane was found to contain unusual lipids, including long-chain (C24-C30) fatty acids (16.8-27.2%) and unconventional 26-alkylated sterols (66.4-72.6%), in addition to more conventional fatty acids and sterols. Spherulous cell intracellular membranes were also found to contain long-chain fatty acids and unconventional sterols, although the relative importance of these unusual lipids apparently varies between intracellular membranes, with some containing approximately 50% long-chain acids.
Subcellular fractionation by differential centrifugation was performed on two previously unstudied marine sponges (Reniera sp. and Pseudaxinyssa sp.) that represent both major subclasses of the Demospongiae. Long chain fatty acids (LCFA) with 24-30 carbon units were found as major constituents of cell membrane isolates of both sponges. Most LCFA were polyunsaturated and were constituents of the phospholipids, which are typical membrane lipids, and in particular the amino-phospholipids. The LCFA composition of phospholipids from whole sponge tissue was shown to provide a reliable indication of the LCFA composition of cell membrane phospholipids in the sponges studied. An unusual triply branched C16 isoprenoid fatty acid, 4,8,12-trimethyltridecanoic acid, also was identified as a cell membrane acid in the sponge Pseudaxinyssa sp.
Subcellular fractionation by differential centrifugation was performed on two previously unstudied marine sponges that predominantly contain either conventional (Reniera sp.) or unconventional (Pseudaxinyssa sp.) sterols. Direct evidence for the presence of unconventional sterols with C24 alkylated side chains in the cellular membranes of Pseudaxinyssa sp. is provided, but the presence of unconventional sterols in sponge membranes is shown not to be a universal feature of the Porifera. Possible structural and functional roles of unconventional lipid molecules in sponge cell membranes are discussed.
The major marine sponge phospholipids 1,2-di-(5Z,9Z)-5,9-hexacosadienoyl phosphatidylcholine (PC) and phosphatidyl-ethanolamine (PE) hardly incorporate cholesterol into their liposomal bilayers, as reported earlier. Our previous studies indicated that their synthetic short chain (C18-C24) analogs with the same double bond pattern readily incorporated cholesterol, thus demonstrating the importance of the chain length. In order to investigate the possible role of the unusual delta 5,9 diunsaturation 1,2-di-(6Z,9Z)-6,9-hexacosadienoyl phosphatidylcholine and phosphatidylethanolamine were synthesized and their thermotropic behavior studied. Both analogs shows a transition endoterm at 45 degrees C, while the natural 1,2-di-(5Z,9Z)-5,9-hexacosadienoyl PC and its PE counterpart exhibited it at 42 degrees C. A partial incorporation of cholesterol into liposomal bilayers of 1,2-di-(6Z,9Z)-6,9-hexacosadienoyl PC was observed. Our results suggest that while the chain length is the predominant factor in the interactions of these phospholipids with sterols, the double bond location may also play a contributing role.
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The novel unesterified alkyl glycerol monoethers, (2S)-1-(hexadecyloxy)-2,3-propanediol (1), (2S)-1-(16-methylheptadecyloxy)-2,3-propanediol (2) and (2S)-1-(15-methylheptadecyloxy)-2,3-propanediol (3) were isolated from the marine sponge Tethya aurantia and were characterized by spectroscopic methods. These three saturated ethers as well as a series of alk-1'-enyl glycerol monoethers were also encountered in the phospholipids of the same sponge after reduction with LiAlH4. Incorporation experiments with dissociated cells of T. aurantia indicated that [1-14C]-hexadecanol was incorporated into the unesterified alkyl glycerol monoethers.
The unusual symmetrical molecular species 1,2-di-3,7,11,15-tetramethylhexadecanoyl-sn-glycero-3-phosphoglyce rol, 1,2-di-5,8,11,14-docosatetraenoyl-sn-glycero-3-phosphocholine, 1,2-di-5,9,19-octacosatrienoyl-sn-glycero-3-phosphoethanolamine, and 1,2-di-5,9,23-triacontatrienoyl-sn-glycero-3-phosphoethanolamine were isolated from the marine sponges Axinella verrucosa, Higginsia tethyoides, Tethya aurantia and Aplysina fistularis by HPLC and studied by fast atom bombardment (FAB) mass spectrometry. In addition to molecular weights, branching and double bonds were located in the fatty acyl chains of the intact phospholipid molecules, using FAB either in a positive or negative mode. Some mass spectral results were obtained on enriched phospholipid fractions rather than pure molecular species using MS/MS.
Liposomes composed of 1,2-di-(5Z,9Z)-5-9-hexacosadienoyl-sn-glycero-3-pho sph ocholine underwent an endothermic phase transition at 42 degrees C. Cholesterol or the marine sterols studied did not affect this transition to an appreciable extent, but rather were excluded from the phospholipid bilayers. Membranes composed of 1,2-di-(5Z,9Z)-5,9-hexacosadienoyl-sn-glycero-3-pho sph ocholine displayed very similar phase properties. Effects of the marine sterols on dipalmitoylphosphatidylcholine bilayers were also investigated.
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Twelve stanols possessing the rare 5 beta-dihydro nucleus have been isolated from the marine sponge Petrosia ficiformis. These stanols have not previously been encountered in any samples of P. ficiformis which we have examined and appear to be the result of bacterial metabolism of the endogenous sponge sterols.
The phospholipids of the sponge Polymastia gleneni contain saturated long chain (C22-30)-acetoxy fatty acids. Their structures were assigned based on chromatographic and spectrometric data as well as comparison with a synthetic sample. The use of capillary gas chromatography combined with chemical ionization and electron impact mass spectrometry was instrumental in the eludication of structures, since only a very small amount of crude lipids was available.
The isolation, structure determination and synthesis of ergosta-5, 24(28), 25-trien-3 beta-ol, as well as the synthesis of its 28-14C analog--a possible biosynthetic precursor of several marine sterols--is described.
13C/12C ratios of sets of compounds, algal sterols and terpenes, isolated from dinoflagellate symbiont (zooxanthellae)-bearing soft corals and gorgonians were determined. In most cases, a significant difference was found between the delta 13C values of the terpenes and of the algal sterols from the same set, the algal sterols containing less 13C than the terpenes. These results can only be explained if terpenes are synthesized by the host. Cultured zooxanthellae, isolated from symbiotic associations, do not make terpenes. Algal sterols of the various sets do not all have the same delta 13C value: average values range from -18.2 to -24.3%. A consistent difference of about 7% in the delta 13C values of sterols of cultured symbionts isolated from two of the gorgonians was found. This has potential applications for the taxonomy of zooxanthellae, most of which are believed by some specialists to be one discrete species.
The phospholipids of the sponge Strongylophora durissima were analyzed. The major phospholipids present were phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylglycerol (PG) and phosphatidylinositol (PI). The major fatty acid components of the phospholipids consisted of short chain (C14-C19) and very long chain (C25 -C30) "Demospongic" acids. Three novel branched delta 5 monounsaturated acids, Z-19-methyl-5-pentacosenoic, Z-19-methyl-5-hexacosenoic and Z-19-methyl-5-heptacosenoic acids were encountered in the sponge. The 3-saturated counterparts of these compounds, 19-methylpentacosanoic, 19-methylhexacosanoic and 19-methylheptacosanoic acids, as well as 19-methyltetracosanoic and 20-methyloctacosanoic acids also are hitherto undescribed acids present in the sponge. Trace amounts of 2 very long chain acids also were detected and their structures tentatively assigned as 19,21-dimethylheptacosanoic and 20,22-dimethyloctacosanoic acids. The distribution of these fatty acids according to phospholipid head groups also was described.
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