Squalene-2,3-oxide-cycloartenol cyclase

The enzyme involved is squalene 2,3-oxide cycloartenol cyclase and the substrate is the S enantiomer. The reaction is initiated by H" " attack on the oxygen of the epoxy group of the substrate held in the chair, boat, chair, boat unfolded conforma-... 

The enzyme squalene-2,3,-oxide-cycloartenol cyclase is inhibited by a series of compounds designed to mimic the carbocationic intermediates that are postulated to participate in the reaction process (Goad, 1991b). 

Cycloartenol (3) is the major product of condensation of squalene 2,3-epoxide (2) by a chair-boat-chair-boat transition state in plants. This condensation is effected by squa-lene-2,3-oxide-cycloartenol cyclase (Fig. 23.6). Micro-somes from Rabdosia japonica (Acanthaceae) showed activity for cyclizing squalene 2,3-epoxide into cycloartenol, 3-amyrin, and a-amyrin. Purified cycloartenol cyclase had a molecular weight of 54,000 (Abe et al., 1989a, 1989b). 

In addition to the squalene oxide to cycloartenol cyclase, the set of phytosterol enzymes- the S-adenosyl-L-methionine C-24 methyl transferases (SMT) and the 9,19-cyclopropyl to 8- isomerase (COI) are considered as phylogenetically significant to plant evolution. The plant SMT is assumed to catalyze Re-face methylation of bent... 

Recent mechanism studies involving incubations with stable isotopes (66,69,70) and studies by us on conformiational analysis (38-42), distribution (7), structure-function/metabolism relationships (54, 55) and mechanistic enzymology of sterol transformation (12,56), negate the otherwise attractive explanation hypothesized by Ourisson et al, (9,10) for evolution of the sterol pathway beginning with the cycloartenol-based pathway. The new data indicate that the lanosterol-based pathway may have evolved before cycloartenol-based pathway, the squalene-oxide cyclase and... 

Formation of sterols from squalene involves cyclization. First a microsomal mixed-function oxidase (squalene epoxidase) forms squalene-2,3-oxide in the presence of NADPH, FAD and O2 (there is no requirement for cytochrome P450 in this reaction). The cyclization of the oxide to lanosterol then takes place by a concerted reaction without the formation of any stable intermediates. This conversion, which has been described as the most complex known enzyme-catalysed reaction, depends on a cyclase with a molecular mass of only 90kDa. In plants and algae squalene-2,3-epoxide is cyclized to cycloartenol which is the precursor of stigmasterol whereas lanosterol is the precursor of cholesterol and ergosterol (Figure 7.19). 

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