High impact information on C05437

• ERG26 encodes 4alpha-carboxysterol-C3 dehydrogenase, one of three enzymatic activities required for the conversion of 4,4-dimethylzymosterol to zymosterol [1].
• Two-hybrid analysis indicated that Erg25p, Erg26p, and Erg27p, which are required for the biosynthesis of zymosterol, form a complex within the cell [1].
• Where examined, cholesterol is synthesized in the endoplasmic reticulum; however, its precursor, zymosterol, is found mostly in the plasma membrane [2].
• In tracing its movements, we have now established the following: (a) in human fibroblasts, zymosterol is converted to cholesterol solely in the rough ER [2].
• In contrast to the yeast SMT where cycloartenol fails to bind to the SMT and zymosterol is the best substrate for methylation, the sunflower SMT studied here utilizes cycloartenol preferentially to zymosterol and the other substrates [3].

Biological context of C05437

• Biomimetic studies of acid-catalysed isomerization of zymosterol resulted in formation of cholest-8(14)-enol, whereas the enzyme-generated product was a Delta(7)-sterol, suggesting absolute stereochemical control of the reaction by hSI [4].
• Substrate protection with zymosterol, 24(28)-methylenelophenol against 26,27-DHZ and similar inhibition of the first and second C(1)-transfer activities by the reversible inhibitor 25-AC of K(i) 20 nM suggested the analogs interacted at the same active site [5].
• Both compounds inhibited cell proliferation, were fungistatic, interrupted the yeast-like-form to germ-tube-form transition, and resulted in the accumulation of zymosterol and related delta24-sterols concurrent with a decrease in ergosterol, as was expected for the specific inhibition of SMT activity [6].
• Zymosterol, a MAS active substance, induced resumption of meiosis in oocytes from Lxrab(-/-) mice, but significantly less effectively than in oocytes from wild type mice [7].

Anatomical context of C05437

• Three lines of evidence suggested that biosynthetically labeled zymosterol was associated with the plasma membrane [8].
• Zymosterol is located in the plasma membrane of cultured human fibroblasts [8].

Associations of C05437 with other chemical compounds

• 2) Sucrose density gradient analysis of homogenates showed that the equilibrium buoyant density profile of newly synthesized zymosterol was identical with that of the plasma membrane [8].
• In the presence of azasterols, S. cerevisiae produces increased amounts of zymosterol, decreased amounts of ergosterol and ergostatetraenol, and the new metabolites cholesta-7,24-dienol, cholesta-5,7,24-trienol, and cholesta-5,7,22,24-tetraenol [9].
• This yeast strain, which is a double mutant of the ERG6 (sterol transmethylase) and ERG2 (C-8 sterol isomerase) genes, accumulates zymosterol as its major sterol component [10].
• This suggests that in the biosynthetic pathway of ergosterol in Schizosaccharomyces species, the transmethylation process on the C-24 may occur directly on lanosterol and not only on zymosterol [11].

Gene context of C05437

• Exogenously-supplied zymosterol is entirely transformed into ergosterol, which represses ERG2 transcription [12].
• Later involvement of this enzyme in postsqualene cholesterol biosynthesis was postulated (conversion of zymosterone to zymosterol) and could be proven in vitro [13].
• Both A. thaliana and one N. tabacum SMT cDNAs were expressed in a yeast null mutant erg6, deficient in AdoMet zymosterol C24-methyltransferase and containing C24-non-alkylated sterols [14].

Analytical, diagnostic and therapeutic context of C05437

• Gas chromatography/mass spectrometry analyses of sterols in this mutant, designated erg26-1, revealed the aberrant accumulation of a 4-methyl-4-carboxy zymosterol intermediate, as well as a novel 4-carboxysterol [1].

References