Research paperModification of the sterol composition of Trypanosoma (Schizotrypanum) cruzi epimastigotes by Δ24(25)-sterol methyl transferase inhibitors and their combinations with ketoconazole
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2021, Journal of Inorganic BiochemistryFunctional importance for developmental regulation of sterol biosynthesis in Acanthamoeba castellanii
2018, Biochimica et Biophysica Acta - Molecular and Cell Biology of LipidsCitation Excerpt :The substrate specificity of AcCYP51 places C14-demethylation after the first sterol methylation step (Fig. 6). However, while T. cruzi has a single SMT1 which is ∆24(25)- and ∆24(28)-substrate bifunctional capable of generating a single ∆24(28)-Z ethylidene C29 – product [55–57] and green alga SMT is substrate bifunctional capable of generating a single ∆25(27)-C29-sterol product [8], A. castellanii has two SMTs to carry out these sterol methylations at C24 with the second methylation step yielding the 24β-stereochemistry. As we discovered in this investigation through isotopically labeling studies to amoeba, the AcSMT2 (or 28-SMT) can, unlike the T. cruzi SMT1, synthesize the C29-∆25(27)-olefin outcome and the resulting intermediate is precursor to the 7-dehydroporiferasterol and poriferasterol.
Trypanosoma cruzi epimastigotes store cholesteryl esters in lipid droplets after cholesterol endocytosis
2018, Molecular and Biochemical ParasitologyGlycyrrhizic acid attenuates growth of Leishmania donovani by depleting ergosterol levels
2017, Experimental ParasitologySterol methyltransferase a target for anti-amoeba therapy: towards transition state analog and suicide substrate drug design
2017, Journal of Lipid ResearchCitation Excerpt :Recognizing the importance of disrupting carbon flux and 14-methyl substrate homeostasis in ergosterol biosynthesis, we moved next to show the ability to block substrate binding using different inhibitor chemotypes can inhibit SMT activities and in so doing, interfere with trophozoite viability. It has been shown previously that 24(R,S),25-epiminolanosterol (EL = 15, Fig. 7), an analog of the high energy intermediate, namely, a transition state analog formed by methylation of the terminal carbon = carbon bond of zymosterol or cycloartenol (Fig. 7), is a potent inhibitor of the 24-SMT activity in fungi, protozoa, and cultured plant cells (20, 34, 39). Related electronic mimics of the high energy intermediates with positive charges in the side chains located at positions resembling C24 or C25 cations show equal potency against 28-SMT (13, 20).