On the origins of triterpenoid skeletal diversity.

Biosynthesis of 24,25-epoxycholesterol from squalene 2,3;22,23-dioxide.

24(S),25-Epoxycholesterol. Evidence consistent with a role in the regulation of hepatic cholesterogenesis.

▪ Abstract The mammalian cell continuously adjusts its sterol content by regulating levels of key sterol synthetic enzymes and levels of LDL receptors that mediate uptake of cholesterol-laden particles. Control is brought about by sterol-regulated transcription of relevant genes and by regulated degradation of the committed step enzyme HMG-CoA reductase (HMGR). Current work has revealed that proteolysis is at the heart of each of these mechanistically distinct axes. Transcriptional control is effected by regulated cleavage of the membrane-bound transcription factor sterol regulatory element binding protein (SREBP), and HMGR degradation is brought about by ubiquitin-mediated degradation. In each case, ongoing cell biological processes are being harnessed to bring about regulation. The secretory pathway plays a central role in allowing sterol-mediated control of transcription. The constitutively active endoplasmic reticulum (ER) quality control apparatus is employed to bring about regulated destruction of H...

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Proteolysis and sterol regulation

Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase by oxysterol by-products of cholesterol biosynthesis. Possible mediators of low density lipoprotein action.

Isolation of 2,3;22,23-dioxidosqualene and 24,25-oxidolanosterol from yeast.

When yeast was grown in the presence of 10−4 M 3β-(β-dimethylaminoethoxy)-androst-5-en-17-one (DMAE-DHA), the compound 2,3;22,23-dioxidosqualene (DOS) accumulated. Total free sterol was reduced by about 30%, whereas almost no steryl esters were found. The same drug at lower concentration (3×10−6 M) caused a slight increase in steryl ester production, and a 24% reduction in free sterol content. The marked accumulation of ergostra-5,7,22,24(28)-tetraen-3β-ol with 3×10−6 M DMAE-DHA indicated that the C24–28 reductase is especially sensitive to the action of the drug.

The effects of the hypocholesteremic compound 3β-(β-dimethylaminoethoxy)-androst-5-en-17-one on the sterol and steryl ester composition ofSaccharomyces cerevisiae

Ruth B. Field

Papers

Isolation of 2,3;22,23-dioxidosqualene and 24,25-oxidolanosterol from yeast.

The effects of the hypocholesteremic compound 3β-(β-dimethylaminoethoxy)-androst-5-en-17-one on the sterol and steryl ester composition ofSaccharomyces cerevisiae