Sterol C5 desaturase

Figure 13.7. The sterols accumulating under azole treatment of C, albicans including the end-product, l4oi-methylergosta-8,24(28)-dien-33,6a-diol, that does not support growth and requires sterol C5-desaturase for biosynthesis. In most fungi, the substrate for CYP5I is more likely eburicol under normal conditions, and not lanosterol, although both are metabolized.

C5-desaturase mutants of C. albicans confirmed the central role of this biotransformation in the mode of action in a clinical setting Sterol profiles of untreated and treated C. albicans illustrate the major sterols accumulating in wild-type and sterol C5-desaturase defective mutants (Figure 13.7). 

Other C. albicans resistant trains have shown defective sterol C5-desaturase activities, including some from AIDS patients and from patients suffering infections as a result of leukemia ... 

Noda, H. and Y. Koizumi (2003). Sterol biosynthesis by symbiotes Cytochrome P450 sterol C5-desaturase genes from yeastlike symbiotes of rice planthoppers and anobiid beetles. Insect Biochem. Mol. Biol. 33, 649-658. 

Taton, M. and Rahier, A. (1996) Plant sterol biosynthesis identification and characterization of higher plant A 7-sterol C5(6)-desaturase. Arch. Biochem. Biophys., 325, 279-88. 

PLANT STEROL BIOSYNTHESIS IDENTIFICATION AND CHARACTERIZATION OF A -STEROL C5(6)-DESATURASE... 

Investigations of the redox proteins and electron transport chain involved in the A -sterol C5(6) desaturase. 

Plant Sterol Biosynthesis Identification and Characterization of A " -Sterol C5(6)-Desaturase. 

Taton M, Husselstein T, Benveniste P, Rahier A. 2000. Role of highly conserved residues in the reaction catalyzed hy recomhinant A(7)-sterol-C5(6)-desaturase smdied by site-directed mutagenesis. Biochemistry 39 701-711. 

Insertion of the C5,6 double bond (A -> A ) involves removal of the 5a (ex 4-pro-R H of MVA) and 6a (ex 5-pro-S H of MVA) hydrogens. In rat liver and yeast microsomal preparations the reaction requires aerobic conditions and NADH or NADPH and both of the eliminated hydrogens are found in HjO. This suggests a mechanism in which hydroxyla-tion at CS or C6 is followed by dehydration across these two carbons or, alternatively, a fatty acid-type desaturation. There is evidence of the former in yeast, whereas the latter seems more likely in rat liver where the multienzyme complex catalysing it consists of the A -desaturase itself, cytochrome and an NAD(P)H-dependent flavoprotein the A -desaturase is a monooxygenase whieh uses electrons derived from NAD(P)H, via the flavoprotein and cytochrome i>5, and O2 to effect the removal of the two hydrogens from the sterol. 

The C5(6) desaturase is a membrane bound enzyme localized in the endoplasmic reticulum, and for the first time, we have developped an enzymatic bioassay. The enzymatic A -sterol fomied was detected using its typical UV absorbance at 281,5 nm. The properties of the microsomal system have been studied and the kinetics of the desaturation reaction has been established [1]. 

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