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The use of stable and radioactive sterol tracers as a tool to investigate cholesterol degradation to bile acids in humans in vivo
Full text linkAlterations of cholesterol homeostasis represent important risk factors for atherosclerosis and cardiovascular disease. Different clinical-experimental approaches have been devised to study the metabolism of cholesterol and particularly the synthesis of bile acids, its main catabolic products. Most evidence in humans has derived from studies utilizing the administration of labeled sterols; these have several advantages over in vitro assay of enzyme activity and expression, requiring an invasive procedure such as a liver biopsy, or the determination of fecal sterols, which is cumbersome and not commonly available. Pioneering evidence with administration of radioactive sterol derivatives has allowed to characterize the alterations of cholesterol metabolism and degradation in different situations, including spontaneous disease conditions, aging, and drug treatment. Along with the classical isotope dilution methodology, other approaches were proposed, among which isotope release following radioactive substrate administration. More recently, stable isotope studies have allowed to overcome radioactivity exposure. Isotope enrichment studies during tracer infusion has allowed to characterize changes in the degradation of cholesterol via the “classical” and the “alternative” pathways of bile acid synthesis. Evidence brought by tracer studies in vivo, summarized here, provides an exceptional tool for the investigation of sterol metabolism, and integrate the studies in vitro on human tissue
Synthesis of chondrillasterol and spinasterol [(22E,24R)- and (22E,24S)-5α-stigmasta-7,22-dien-3β-ol]
No full textSpinastesterol (1a) and chrondrillasterol (1b) have been synthesized from the ethyl (22E,24S)- and (22E,24R)-3β-acetoxy-5α-stigmasta-7,22-dien- 29-oates, (2c) and (2d), respectively
A new route to steroid ring-c aromatization from 7-oxygenated steroids
No full text3β-Acetoxy-5α-cholesta-8,14-dien-7β-ol (3), 3β-acetoxy-8α,9α-epoxy-5α-cholestan-7β-ol (6a), and 3β-acetoxy-8α, 14α-epoxy-5α-cholestan-7β-ol (8a) have been aromatized with hydrochloric acid in ethanol to afford a 9 : 1 mixture of 12-methyl-18-nor-5α,17β(H)-cholesta-8,11,13-trien-3β-ol (4) and 12-methyl-18-nor-5α-cholesta-8,11,13-trien-3β-ol (5). By the same acidic treatment 3β-acetoxy-8α,9α-epoxy-5α-cholestan-7α-ol (6c) generates 3β-hydroxy-5α-cholest-8-en-7-one (7a), and 3β-acetoxy-8α, 14α-epoxy-5α-cholestan-7α-ol (8c) affords 3β-hydroxy-5α-cholest-8(14)-en-7-one (9a) accompanied by the previously unobserved 3β-hydroxy-5α-cholest-8(14)-en-15-one (10a)
Synthesis of castasterone and its 22S,23S-isomer: Two plant growth promoting ketones
No full textCastasterone (22R,23R,24S)-2α,3α,22,23-tetrahydroxy-5α- ergostan-6-one (1) and its (22S,23S)-isomer have been synthesized from (20S)-6β-acetoxy-3α,5-cyclo-5α-pregnane-20-carbaldehyde. The side chain with the correct stereochemistry was constructed via a Claisen rearrangement and the nuclear functionalities were introduced by osmilation of the intermediate obtained by opening of the cyclopropane ring with hydrochloric acid and dehydrohalogenation
Kinetics and metabolism of CDP-METHYL- [C-14] choline after intravenous and oral-administration to rats
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Oxysterols in bile acid metabolism
No full textIncreasing body of evidence is available indicating that oxysterols are more much than intermediates of metabolic pathways. Oxysterols play a role in the regulation of cholesterol synthesis, transport and efflux. A scavenger effect of cholesterol 27-hydroxylase on elevated serum cholesterol levels is well demonstrated. Bile acid synthesis occurs through two main pathways, the classic and the alternative ones. Since plasma concentrations of 27-hydroxycholesterol were clearly shown to reflect its production rate the alternative pathway of bile acid synthesis can be easily explored. Conversely this was not true for 7α-hydroxycholesterol and also the direct evaluation of the classic pathway by kinetic studies is more difficult since the rate of plasma appearance during continuous infusion of deuterated isotopomers may not exactly measure its production rate. Hepatic cholesterol 7alpha-hydroxylase activity is absent during fetal life in humans and upregulates after birth. Both the classic and alternative pathways become mature after the age of 4 years. It has been clearly demonstrated that in patients with liver disease the classic pathway is impaired while the alternative one is preserved. Conversely, in obese patients, preliminary data suggest an increase of the production rate of 27-hydroxycholesterol, a possible mechanism to counteract the increase of atherosclerotic risk
Hydrolytic conditions for the formation of open-chain oligopeptides from cyclosporin A
No full textIn this work we report data on the hydrolysis of CsA, allowing interpretation on the formation of
previously identified open chain oligopeptides from CsA
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