Membrane-sterol

Wiseman H, Cannon M, Arnstein HR, Barlow DJ (1992a) The structural mimicry of membrane sterols by tamoxifen evidence from cholesterol coefficients and molecular-modelling for its action as a membrane anti-oxidant and an anti-cancer agent. Biochim Biophys Acta 1138(3) 197-202... 

Amphotericin B Cholesteryl (Amphotec) [Antifungal/Polyene Mocrollde] Uses AspCTgillosis if intolCTant/refractory to conventional amphotericin B, systemic candidiasis Action Binds ceU membrane sterols, alters permeability Dose Adults Peds. Test dose 1.6—8.3 mg, over 15-20 min, then 3-4 mg/kg/d 1 mg/kg/h inf w/ renal insuff Caution [B, ] Disp Inj SE Anaphylaxis fever, chills, HA, nephrotox, -1- BP, anemia Notes Do not use in-line filter Interactions See Amphotericin B EMS See AmphotCTicin B OD May cause cardiac arrest s ptomatic and supportive... 

Elias, P. M., Friend, D. S. and Goerke, J. 1979. Membrane sterol heterogeneity. Freeze-fracture detection with saponins and filipin. J. Histochem. Cytochem. 27, 1247-1260. 

This primary mode of action of tomatine, that involves the formation of complexes with membrane sterols is similar to that described for polyene antibiotics [2, 4], and results in pore formation and loss of membrane integrity. This mode of action is supported by the reduced activity of tomatine on sterol-free bacteria and Oomycete fungi such as Pythium and Phytophthora [15, 28], and the strongly reduced toxicity of hydrolysis products of the glycoalkaloid which fail to bind sterols [57]. 

In vitro studies by Roddick and Drysdale on the effect of tomatine on the leakage of peroxidases from liposomes also support the idea that tomatine binds membrane sterols. They detected a significant disruption of the liposome by tomatine, only if the membranes contained sterol and additionally this destabilization was pH-dependent [27]. Later it was demonstrated that liposome membranes containing sterols but lacking 30-hydroxy sterol were resistant to tomatine [28]. 

Mechanism of Action. Like the systemic azoles, clotrimazole and other topical antifungal azoles work by inhibiting the synthesis of key components of the fungal cell membrane that is, these drugs impair production of membrane sterols, triglycerides, and phospholipids.9 Loss of these components results in the membrane s inability to maintain intracellular homeostasis, leading to death of the fungus. 

Interaction with membrane sterols, formation of membrane channels... 

Some allelochemicals have hemolytic properties, such as saponins. If resorbed, these compounds complex membrane sterols and make the cells leaky. Steroidal alkaloids from Solanum or Veratrum species display this sort of activity as well as influencing ion channels (Table IV). 

Goldstein, J. L., DeBose-Boyd, R. A., Brown, M. S. (2006). Protein sensors for membrane sterols. Cell, 124, 35-46. 

The formation of a complex with membrane sterols requires penetration of the glycoside into the membrane (corresponding blocks are connected by an arrow). Owing to the ability of an aglycon to form a complex [175] the corresponding block is connected with the structural elements related to an aglycon part of the molecule. The stereochemistry of lanostane nucleus plays a major role in the formation of this complex, besides, the presence of 18(20)-lactone is also important [9, 42] (these functional relations are depicted by bold arrows). 

Goldstein JL, DeBose-Boyd RA, Brown MS (2006) Protein sensors for membrane sterols. Cell 124 35 6 Gombos I, Bacso Z, Detre C, et al. (2004) Cholesterol sensitivity of detergent resistance a rapid flow cy-... 

Suzuki, F. and Yanagimachi, R. (1989). Changes in the distribution of intramembraneous particles and filipin-reactive membrane sterols during in vitrol capacitation of golden hamster spermatozoa. Gamete Res. 23 335-347. 

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