MARINE STEROLS: VI. STEROL BIOSYNTHESIS IN MOLLUSCS AND ECHINODERMS

1960 ◽  
Vol 38 (1) ◽  
pp. 997-1002 ◽  
Author(s):  
U. H. M. Fagerlund ◽  
D. R. Idler
Keyword(s):  
Sterol Biosynthesis ◽  
Major Portion ◽  
Mytilus Californianus ◽  
Polar Zone ◽  
Pisaster Ochraceus ◽  
Saxidomus Giganteus

The in vivo incorporation of 2-C14-acetate into digitonin-precipitable material has been demonstrated in two molluscs, mussel (Mytilus californianus) and clam (Saxidomus giganteus). Clams are able to convert 11,14-C14-squalene into digitonin-precipitable material. When the azoylester of the material isolated from clams is chromatographed, the major portion of the radioactivity follows the least polar zone, which has previously been found to contain mainly monounsaturated Δ5-sterols.A starfish (Pisaster ochraceus) has been shown in vivo to convert ingested 4-C14-cholesterol to 7-cholestenol.

MARINE STEROLS: VI. STEROL BIOSYNTHESIS IN MOLLUSCS AND ECHINODERMS

1960 ◽  
Vol 38 (9) ◽  
pp. 997-1002 ◽  
Author(s):  
U. H. M. Fagerlund ◽  
D. R. Idler
Keyword(s):  
Sterol Biosynthesis ◽  
Major Portion ◽  
Mytilus Californianus ◽  
Polar Zone ◽  
Pisaster Ochraceus ◽  
Saxidomus Giganteus

The in vivo incorporation of 2-C14-acetate into digitonin-precipitable material has been demonstrated in two molluscs, mussel (Mytilus californianus) and clam (Saxidomus giganteus). Clams are able to convert 11,14-C14-squalene into digitonin-precipitable material. When the azoylester of the material isolated from clams is chromatographed, the major portion of the radioactivity follows the least polar zone, which has previously been found to contain mainly monounsaturated Δ5-sterols.A starfish (Pisaster ochraceus) has been shown in vivo to convert ingested 4-C14-cholesterol to 7-cholestenol.

MARINE STEROLS: IX. BIOSYNTHESIS OF 24-METHYLENECHOLESTEROL IN CLAMS

1961 ◽  
Vol 39 (9) ◽  
pp. 1347-1355 ◽  
Author(s):  
U. H. M. Fagerlund ◽  
D. R. Idler
Keyword(s):  
Digestive Gland ◽  
Saxidomus Giganteus

Clams (Saxidomus giganteus) are able to transform injected cholesterol-4-C14 into radioactive 24-methylenecholesterol in vivo. The highest rate of conversion was observed when the radioactive sterol was injected into the digestive gland. The findings suggest a possible pathway in the biosynthesis of C28-sterols and throw some light on the question of the origin of C28-sterols in lamellibranchs.

Lipid biosynthesis pathways as chemotherapeutic targets in kinetoplastid parasites

Parasitology ◽  
1997 ◽  
Vol 114 (7) ◽  
pp. 91-99 ◽  
Author(s):  
J. A. URBINA
Keyword(s):  
Trypanosoma Cruzi ◽  
Recent Work ◽  
Chagas Disease ◽  
Pneumocystis Carinii ◽  
Lipid Biosynthesis ◽  
Sterol Biosynthesis ◽  
Leishmania Braziliensis ◽  
Biosynthesis Inhibitors

Inhibitors of sterol and phospholipid biosynthesis in kinetoplastid parasites such as Trypanosoma cruzi, the causative agent of Chagas' disease, and different species of Leishmania have potent and selective activity as chemotherapeutic agents in vitro and in vivo. Recent work with the sterol C14α-demethylase inhibitor D0870, a bis triazole derivative, showed that this compound is capable of inducing radical parasitological cure in murine models of both acute and chronic Chagas' disease. Other inhibitors of this type, such as SCH 56592, have also shown curative, rather than suppressive, activity against T. cruzi in these models. Leishmania species have different susceptibilities to sterol biosynthesis inhibitors, both in vitro and in vivo. Leishmania braziliensis promastigotes, naturally resistant to C14α-demethylase inhibitors such as ketoconazole and D0870, were susceptible to these drugs when used in combination with the squalene epoxidase inhibitor terbinafine. Inhibitors of Δ24(25) sterol methyl transferase have been shown to act as potent antiproliferative agents against Trypanosoma cruzi, both in vitro and in vivo. New inhibitors of this type which show enhanced activity and novel mechanisms of action have been synthesized. Recent work has also demonstrated that this type of enzyme inhibitors can block sterol biosynthesis and cell proliferation in Pneumocystis carinii, a fungal pathogen which had previously been found resistant to other sterol biosynthesis inhibitors. Ajoene, an antiplatelet compound derived from garlic, was shown to have potent antiproliferative activity against epimastigotes and amastigotes of Trypanosoma cruzi in vitro; this activity was associated with a significant alteration of the phospholipid composition of the cells with no significant effects on the sterol content. In addition, alkyllsophospholipids such as ilmofosine, miltefosine and edelfosine have been shown to block the proliferation of T. cruzi and Leishmania and alter both the phospholipid and sterol composition. These results indicate the potential of lipid biosynthesis inhibitors as useful therapeutic agents in the treatment of leishmaniasis and Chagas' disease.

Paralytic Shellfish Poison and Melanin Distribution in Fractions of Toxic Butter Clam (Saxidomus giganteus) Siphon

1972 ◽  
Vol 29 (11) ◽  
pp. 1657-1658 ◽  
Author(s):  
R. J. Price ◽  
J. S. Lee
Keyword(s):  
Binding Agent ◽  
Paralytic Shellfish Poison ◽  
Paralytic Shellfish ◽  
Saxidomus Giganteus

Frozen toxic butter clam (Saxidomus giganteus) siphons were fractionated and each fraction was bioassayed for paralytic shellfish poison (PSP) and chemically analyzed for melanin. Sonication removed over 50% of the melanin from the siphons and this fraction contained nearly 50% of the PSP initially present in the siphons. The data presented further implicate melanin as a PSP binding agent in vivo.

scholarly journals Novel Antifungal Drug Discovery Based on Targeting Pathways Regulating the Fungus-Conserved Upc2 Transcription Factor

2013 ◽  
Vol 58 (1) ◽  
pp. 258-266 ◽  
Author(s):  
Christina Gallo-Ebert ◽  
Melissa Donigan ◽  
Ilana L. Stroke ◽  
Robert N. Swanson ◽  
Melissa T. Manners ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Dna Binding ◽  
Fungal Pathogens ◽  
Direct Interaction ◽  
Antifungal Drugs ◽  
Sterol Biosynthesis ◽  
Content Type ◽  
Stressed Cells

ABSTRACTInfections byCandida albicansand related fungal pathogens pose a serious health problem for immunocompromised patients. Azole drugs, the most common agents used to combat infections, target the sterol biosynthetic pathway. Adaptation to azole therapy develops as drug-stressed cells compensate by upregulating several genes in the pathway, a process mediated in part by the Upc2 transcription factor. We have implemented a cell-based high-throughput screen to identify small-molecule inhibitors of Upc2-dependent induction of sterol gene expression in response to azole drug treatment. The assay is designed to identify not only Upc2 DNA binding inhibitors but also compounds impeding the activation of gene expression by Upc2. An AlphaScreen assay was developed to determine whether the compounds identified interact directly with Upc2 and inhibit DNA binding. Three compounds identified by the cell-based assay inhibited Upc2 protein level andUPC2-LacZgene expression in response to a block in sterol biosynthesis. The compounds were growth inhibitory and attenuated antifungal-induced sterol gene expressionin vivo. They did so by reducing the level of Upc2 protein and Upc2 DNA binding in the presence of drug. The mechanism by which the compounds restrict Upc2 DNA binding is not through a direct interaction, as demonstrated by a lack of DNA binding inhibitory activity using the AlphaScreen assay. Rather, they likely inhibit a novel pathway activating Upc2 in response to a block in sterol biosynthesis. We suggest that the compounds identified represent potential precursors for the synthesis of novel antifungal drugs.

Ciba Foundation Study Group No. 4: Virus Virulence and Pathocenicity, G.E.W. Wolstenholme, and C.M. O'Connor, Eds. Boston, Little, Brown and Co., 1960, 114 pp

PEDIATRICS ◽  
1960 ◽  
Vol 26 (5) ◽  
pp. 821-821
Author(s):  
Henry C. Cramblett
Keyword(s):  
Influenza Virus ◽  
In Vitro Culture ◽  
Major Portion ◽  
Study Group ◽  
Culture Systems

This book contains the papers presented by various investigators in the Ciba Foundation Conference concerned with virus virulence and pathogenicity. The participants were investigators noted for their excellence in virologic research. The various factors known to effect virulence and pathogenicity of viruses in in-vitro culture systems as well as in vivo in humans are well elucidated. Although the influenza virus was used as the model for a major portion of the discussions, other viruses were also considered.

MARINE STEROLS: VIII. IN VIVO TRANSFORMATIONS OF THE STEROL SIDE CHAIN BY A CLAM

1961 ◽  
Vol 39 (3) ◽  
pp. 505-509 ◽  
Author(s):  
U. H. M. Fagerlund ◽  
D. R. Idler
Keyword(s):  
Sterol Fraction ◽  
Side Chain ◽  
Saxidomus Giganteus

Analysis of the ozonolysis products of a sterol fraction obtained from clams (Saxidomus giganteus) injected with cholesterol-26-C14 has demonstrated that these molluscs are able to introduce unsaturation into the cholesterol side chain at C-22 and C-25.

Isolation, stereochemistry, and biosynthesis of Šormosterol, a novel cyclopropane-containing sponge sterol

1991 ◽  
Vol 56 (5) ◽  
pp. 1093-1105 ◽  
Author(s):  
Christopher J. Silva ◽  
Carl Djerassi
Keyword(s):  
Double Bond ◽  
Marine Sponge ◽  
Cyclopropane Ring ◽  
Sterol Biosynthesis ◽  
Side Chain ◽  
Alternative Product

Šormosterol ((24R)-24,25-methylenecholesterol, XVIII, a product of the novo sterol biosynthesis in the marine sponge Lissodendoryx topsenti, was shown, trough the use of suitably labeled precursors, to be a new alternative product of the initial S-adenosylmethionine (SAM) methylation of the 24,25 double bond in the sterol side chain. Additional labeling experiments demonstrated that the cyclopropane ring is not further modifies in vivo by the sponge.

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