Ergosterol mutants

Ag-isomerase leading to depletion of ergosterol and accumulation of an unplanar sterol ignosterol. With the inhibition of two steps in the same pathway, a natural synergistic effect is built into the molecule so that the risk of appearance of resistant mutants is low and efficacy high. 

Rahier and his co-workers also characterized the activities of a sterol C-4 methyl oxidase (SMO), a 4-carboxysterol-3-hydroxysteroid dehydrogenase/ C-4 decarboxylase (3-HSD/D) and an NADPH-dependent 3-oxosteroid reductase in order to define the steps involved in C-4 demethylation in plants (Pascal et al, 1993 Rondet et al, 1999). Only recently, they have isolated two cDNAs from Arabidopsis thaliana encoding bifunctional 3-HSD/D. Transformation of a yeast ergosterol auxotroph mutant, which lacks 3-HSD/D activity, with either of these cDNAs restored ergosterol biosynthesis in the yeast mutant (Rahier et al, 2006). 

A recent study has examined the reaction between Cr(VI) and plasma cell membranes in parental (ergosterol-producing, 33 erg ) and mutant (ergosterol-free, erg-2) strains of an eukaryotic yeast, C. albicans (218). In the absence of Cr(VI), the plasma membrane from the erg-2 strain showed greater rigidity than... 

A small group of C albicans mutants, induced by A -methyl-A -nitroso-guanidine, were found to contain more ergosterol than the wild type [311] and it has been suggested that this additional sterol is either re-orientated or masked in some way so that polyene binding is lowered. The observation that sterol incorporation per se does not always increase the polyene sensitivity of liposomes, i.e. it is the membrane state induced by sterol, not the total quantity which confers polyene sensitivity, which may provide a partial explanation of this case. 

Paclobutrazol is a triazole plant growth retardant which also has fungicidal properties [1]. It is an inhibitor of cytochrome P-450 dependant enzymes such as ent-kaurene oxidase and sterol 14a-methyl-demethylase [1]. The fungicidal activity of azole compounds is believed to result from the inhibition of sterol 14a-demethylation. This causes an accumulation of 14a-methylsterols and loss of ergosterol which may have adverse effects on membrane properties [2]. However, there is evidence for other essential requirements for sterol In cell proliferation in addition to a membrane structural role [3-6].For example, in yeast mutants traces of ergosterol stimulate phospholipid formation [7] and protein kinase activity [8]. This report describes the effects of paclobutrazol on the sterol and phospholipid compositions of membranes from plant and yeast cultures. 

There is little doubt that acetate or compounds which may be metabolized by way of a 2-carbon unit are efficient precursors of cholesterol. Acetate, - ethanol, acetone, - acetaldehyde, and to a lesser extent, pyruvate, undergo biolo cal conversion to cholesterol in intact animals and in tissue preparations. Investigations with yeast, as well as with a mutant strain of Neurospora erassa which required acetate for growth, have shown that acetate is the major source of the carbon atoms of ergosterol (XI), a plant sterol. When this mutant was grown on a medium... 

Utilization op O HsC OOH pob Ergosterol Synthesis in Acetatb-lbss Mutant OP Nbubospora (from Bloch i)... 

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