79. The action of selenium dioxide on sterols and bile acids. Part III. Cholesterol

Novel oxysterols observed in tissues and fluids of AY9944-treated rats: a model for Smith-Lemli-Opitz syndrome

“…4 ␣ -and 4 ␤ -Hydroxy-cholesterol were prepared by previously established procedures ( 51,52 ) and their diacetate esters were subsequently converted to 4 ␣ -and 4 ␤ -hydroxy-7-DHC diacetate esters via bromination with N -bromosuccinimide and benzoyl peroxide followed by elimination of this large difference in reactivity toward oxidation, high levels of oxysterols would be expected to form in tissues and fl uids of patients with SLOS, where levels of 7-DHC are also high. Elevated levels of novel 7-DHC-derived oxysterols have been reported in Dhcr7 -defi cient cells and in tissues of Dhcr7 -null mice, but only one of these oxysterols, DHCEO, was identifi ed in cultured cells and in vivo in biological tissues ( 21,32 ).…”

A dietary factor concerned in coprosterol formation

“…Fortunately we had at our disposal a specimen of pure phrenosin, prepared more than 60 years ago by its discoverer Thudichum [see Rosenheim, 1930]. When Thudichum's phrenosin, in amouats proportional to that contained in the brain powder, was added to the standard diet plus cholesterol, the rats excreted coprosterol to the extent of over 80 % of the faecal sterols.…”

“…Phrenosin. The cerebroside fraction of the 'white matter' was separated from sphingomyelin by means of pyridine [Rosenheim, 1914]. The phrenosin fraction, still containing kerasin after fractionation from acetone at 360, was further purified by two recrystallizations from -mixtures of chloroform-acetic acid (2: 3).…”

“…The phrenosin fraction, still containing kerasin after fractionation from acetone at 360, was further purified by two recrystallizations from -mixtures of chloroform-acetic acid (2: 3). The specimens of phrenosin so obtained were still contaminated with appreciable amounts of kerasin, as shown by the selenite plate test [Rosenheim, 1914], but contained only traces of sphingomyelin. Lack of material prevented further purification.…”

“…The seleniteplate test showed complete absence of kerasin. On hydrolysis by the technique described by Rosenheim [1913] phrenosinic acid, sphingosine and galactose were obtained in the usual amounts. Judged by modern standards therefore, this specimen of Thudichum's phrenosin is as pure as any prepared since by later investigators.…”