Biosynthesis of Cholesterol and Other Sterols

Evolutionarily conserved Δ25(27)-olefin ergosterol biosynthesis pathway in the alga Chlamydomonas reinhardtii

“…Using HPLC, we purifi ed four sterols from KD7 and two sterols from KD21. The structures of these compounds were confi rmed by 1 Table I ). Based on spectra of reference materials ( 31,37,38 ), the sterols from the different cell types possessed one or more functional groups of a ⌬ 22 E double bond, Relevant ions for ergosterol appeared at m /-396, 381, 378, and 363 amu and for 7-dehydroporiferasterol at m / z 410, 395, 392, and 377 amu ( Fig.…”

“…2 ). Alternatively, fungi synthesize a 24-SMT that prefers substrates zymosterol or lanosterol, depending on the organism, and a sterol C24(28)-reductase the prefers ergosta-5,7,24(28)-trienol as substrate ( 1 ). In both sterol C-methylation-reduction pathways, the resulting ergosterol contains the same stereochemistry at C24 and C25 ( 1 ).…”

“…Only the lanosterol-based product, however, is further converted to ergosterol because fungi lack enzymes required to open the 9 ␤ ,19-cyclopropane ring system ( 1,2 ). Future studies in progress to determine whether the C. reinhardtii 24-SMT can catalyze lanosterol and cycloartenol to the same set of ⌬ 25 (27) -and ⌬ 24 (28) -C 1 transfer products should further illuminate the evolution of these pathways.…”

Structural complex of sterol 14α-demethylase (CYP51) with 14α-methylenecyclopropyl-Δ7-24, 25-dihydrolanosterol

“…To monitor possible MCP conversion by CYP51 or release of a CYP51-activated MCP intermediate into the media, 1 M of CYP51 from T. brucei and from T. cruzi was incubated with 50 M of radiolabeled MCP (1.88 × 10 9 dpm/mg ) at the standard reaction conditions. Aliquots were taken over time (5,20,40, and 60 min), and the sterols were extracted and analyzed as described above.…”

<i>De Novo</i> Design of Non-coordinating Indolones as Potential Inhibitors for Lanosterol 14-α-Demethylase (CYP51)

“…The design principles were guided by the isosterism observed in molecular fragments of lanosterol 4 and the azoles 5, 16,17) as directed toward the affinity of the hydrophobic residues (Tyr76, Phe78, Met79 Phe83, Arg96, Phe255, Ala256, His259, Leu321, Ile322, Ile323, Met433 and Val434) in the active site of CYP51.…”