The conversion of cholest-5-en-3beta-ol into cholest-7-en-3beta-ol by the echinoderms Asterias rubens and Solaster papposus.

1. The echinoderms Asterias rubens and Solaster papposus (Class Asteroidea) metabolize injected [4(-14)C]cholest-5-en-3beta-ol to produce labelled 5alpha-cholestan-3beta-ol and 5alpha-cholest-7-en-3beta-ol. 2. Conversion of 5alpha-[4(-14)C]cholestan-3beta-ol into 5alpha-cholest-7-en-3beta-ol was demonstrated in A. Rubens. 3. Incubations of A. rubens with [4(-14)C]cholest-4-en-3-one resulted in the production of labelled 5alpha-cholestan-3-one, 5alpha-cholestan-3beta-ol and 5alpha-cholest-7-en-3beta-ol. 4. [4(-14)C]Sitosterol was metabolized by A. rubens to give 5alpha-stigmastan-3beta-ol and 5alpha-stigmast-7-en-3beta-ol. 5. The significance of these results in relation to the presence of alpha7 sterols in starfish is discussed.     

The mechanism of the elaboration of ring b in ergosterol biosynthesis

Methods for the preparation of [3alpha-(3)H]ergosta-7,22-dien-3beta-ol (5,6-dihydro-ergosterol), [5,6-(3)H(2)]ergosta-7,22-dien-3beta-ol and [3alpha-(3)H]ergosta-7,22-diene-3beta,5alpha-diol are described. It is shown that 5,6-dihydro[3alpha-(3)H]ergosterol on incubation under aerobic conditions with whole cells of Saccharomyces cerevisiae LK(2)G(12) is efficiently converted into ergosterol. Studies carried out with dihydro[5alpha,6alpha-(3)H(2)]-ergosterol demonstrate that the introduction of the 5,6-double bond in ergosterol biosynthesis is attended by an overall cis-elimination of two hydrogen atoms. To differentiate between a hydroxylation-dehydration mechanism and a dehydrogenation mechanism, the metabolism of [3alpha-(3)H]ergosta-7,22-diene-3beta,5alpha-diol was studied. It was shown that this diol is converted into ergosterol only under aerobic conditions. It is therefore suggested that the introduction of the 5,6-double bond of ergosterol does not occur through a hydroxylation-dehydration mechanism.     

Synthesis of the marine epoxy sterol 9 alpha,11 alpha-epoxy-5 alpha-cholest-7-ene-3 beta,5,6 beta-triol

The synthesis of 9 alpha,11 alpha-epoxy-5 alpha-cholest-7-ene-3 beta,5,6 beta-triol (1), a highly oxygenated marine sterol containing a 9,11-epoxide moiety in the nucleus, is described. Epoxy sterol 1 was synthesized from cholesta-5,7-dien-3 beta-ol. Oxidation of this sterol with m-chloroperbenzoic acid followed by hydrolysis and acetylation furnished 5 alpha-cholest-7-ene-3 beta,5,6 alpha-triol 3,6-diacetate (2). Mercuric acetate dehydrogenation of diacetate 2, followed by oxidation with manganese dioxide and epoxidation with m-chloroper-benzoic acid, afforded 9 alpha,11 alpha-epoxy-3 beta,5-dihydroxy-5 alpha-cholest-7-en-6-one (5). Reduction of 5 with lithium aluminum hydride gave the desired compound 1. The structures of all synthetic intermediates were confirmed by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. A reassignment of resonances for carbons 1, 8, and 15 in the 13C NMR spectrum of 1, based on 2D-NMR correlation spectroscopy, has been accomplished.     

Evidence for the presence of 7-hydroperoxycholest-5-en-3 beta-ol in oxidized human LDL.

Low density lipoprotein (LDL) cholesterol is known to be oxidized both in vitro and in vivo giving rise to oxygenated sterols. Conflicting results, however, have been reported concerning both the nature and the relative concentrations of these compounds in oxidized human LDL. We examined the extracts obtained from Cu(2+)-oxidized LDL. Thin layer chromatography analysis showed that the sterol mixture became more complex with reaction time. Analysis of the components by thin layer chromatography and mass spectrometry allowed to establish that 7 alpha- and 7 beta-hydroperoxycholest-5-en-3 beta-ol (7 alpha OOH and beta OOH) are largely prevalent among the oxysterols at early times of oxidation. These hydroperoxy derivatives have not been previously identified in oxidized LDL. The concentration of 7-hydroperoxycholest-5-en-3 beta-ol decreased with oxidation time with a concomitant increase of cholest-5-en-3 beta, 7 alpha-diol (7 alpha OH), cholest-5-en-3 beta, 7 beta-diol (7 beta OH), cholesta-3,5-dien-7-one (CD) and cholest-5-en-3 beta-ol-7-one (7CO). After 24 h of oxidation a minor component of the LDL sterols was cholestan-3 beta-ol-5,6-oxide (EP).     

Epoxidation and reduction of cholesterol, 1,4,6-cholestatrien-3-one and 4,6-cholestadien-3beta-ol

Many naturally occurring polyhydroxylated sterols and oxysterols exhibit potent biologic activities. This paper describes reagent and position selectivity of epoxidation and reduction of cholesterol derivatives. Cholesterol was reacted with m-chloroperoxybenzoic acid (m-CPBA) to form 5alpha,6alpha-epoxycholestan-3beta-ol, but in reaction with 30% H(2)O(2), it did not reacted. 1,4,6-cholestatrien-3-one was obtained from cholesterol and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in dioxane. 1,4,6-cholestatrien-3-one was reacted with 30% H(2)O(2) and 5% NaOH in methanol to give 1alpha,2alpha-epoxy-4,6-cholestadien-3-one, which was stereoselectively reduced with NaBH(4) to form 1alpha,2alpha-epoxy-4,6-cholestadien-3beta-ol and reduced with Li metal in absolute ethanol to give 2-ethoxy-1,4,6-cholestatrien-3-one. And 1,4,6-cholestatrien-3-one was epoxidized with m-CPBA in dichloromethane to afford 6alpha,7alpha-epoxy-1,4-cholestadien-3-one, which was reacted with NaBH(4) to synthesize 6alpha-hydroxy-4-cholesten-3-one and reduced Li metal in absolute ethanol to form 2-ethoxy-1,4,6-cholestatrien-3-one, respectively. 1,4,6-cholestatrien-3-one was reduced with NaBH(4) in absolute ethanol to form 4,6-cholestadien-3beta-ol, which was reacted with 30% H(2)O(2) to leave original compound, but was reacted with m-CPBA to give 4beta,5beta-epoxy-6-cholesten-3beta-ol as the major product and 4beta,5beta-epoxy-6alpha,7alpha-epoxycholestan-3beta-ol as the minor product.     

Epoxidation of androsta-5,16-dien-3 beta-ol by hepatic microsomal lipid peroxidation

Male rat liver microsomes oxidized androsta-5,16-dien-3 beta-ol (delta 16-ANDO) to delta 16-ANDO-5,6 alpha-, -5,6 beta-, -16,17 alpha-, and -16,17 beta-epoxides and delta 16-ANDO-5 alpha,6 beta-, -16 alpha,17 beta-, and -16 beta,17 alpha-glycols in the presence of an NADPH-generating system and the microsomal lipid peroxidation accelerator, Fe2+-ADP. The hepatic microsomes hydrolyzed all the delta 16-ANDO epoxides to the glycols. delta 16-ANDO-5 alpha,6 beta-glycol was the sole metabolite from both 5,6 alpha- and 5,6 beta-epoxides. Microsomal epoxide hydrolase also hydrolyzed delta 16-ANDO-16,17 alpha-epoxide specifically to the 16 beta,17 alpha-glycol and the isomeric 16,17 beta-epoxide to the 16 alpha,17 beta- and 16 beta,17 alpha-glycols approximately in the equal ratio. The delta 5-epoxidation of delta 16-ANDO by microsomes occurred only under the conditions that lipid peroxidation took place. Direct evidence was obtained for the participation of microsomal lipid hydroperoxides in the epoxidation of delta 16-ANDO by using photochemically prepared hydroperoxides of phospholipids separated from the hepatic microsomes. The hydroperoxides generated active oxygens, tentatively assigned as alk(ylper)oxy radicals, by the action of ferrous ion and epoxidized delta 16-ANDO to afford the 5,6- and 16,17-epoxides. The Fe2+-ADP-mediated epoxidation of delta 16-ANDO by the phospholipid hydroperoxides occurred preferentially at delta 5 to delta 16 and afforded the 5,6 beta-epoxide in a higher ratio than the 5,6 alpha-epoxide, similar to the Fe2+-ADP-mediated microsomal epoxidation, while the alpha-epoxide was preferentially formed to the beta-epoxide for delta 16 in the epoxidation by both systems.     

Synthesis and bioactivity evaluation of brassinosteroid analogs

Four new analogs of 28-homocastasterone have been synthesized and completely characterized for the first time from stigmasterol. (22R, 23R,24S)-3beta-acetoxy-22,23-dihydroxy-5alpha-stigmastan+ ++-6-one (17), (22R,23R,24S)-3beta-bromo-22,23-dihydroxy-5alpha-stigmast an-6-one (18), (22R,23R,24S)-3beta-acetoxy-5,22, 23-trihydroxy-5alpha-stigmastan-6-one (20), and (22R,23R, 24S)-3beta-bromo-5,22,23-trihydroxy-5alpha-stigmastan-6-one (21), were obtained through a synthetic route based on regioselective Delta(5) epoxidation. Compounds 17 and 18, bearing a 5alphaH moiety, were prepared through a reductive opening of the 5beta,6beta epoxy precursor, and compounds 20 and 21, analogs with a 5alphaOH moiety were obtained by hydrolytic opening of a mixture of 5alpha,6alpha and 5beta,6beta epoxy precursors. Known compounds 19 and 22 were also obtained following the described synthetic routes, respectively. The new compounds were tested with the traditional auxin-like bioassay for brassinosteroids with 19 and 22 as standards. All compounds were comparatively evaluated for their inhibitory effect on the replication of DNA (HSV-1) virus.     

Concurrent occurrence of 3 beta,12 alpha-dihydroxy-5-cholenoic acid associated with 3 beta-hydroxy-5-cholenoic acid and their preferential urinary excretion in liver diseases

3 beta-Hydroxy-(delta 5-3 beta-ol), 3 beta,12 alpha-dihydroxy-(delta 5-3 beta,12 alpha-ol), 3 beta,7 alpha-dihydroxy-(delta 5-3 beta,7 alpha-ol) and 3 beta,7 beta-dihydroxy-(delta 5-3 beta,7 beta-ol) 5-cholenoic acids were identified in patients with liver diseases by gas-liquid chromatography-mass spectrometry (GLC-MS). Of these unusual 3 beta-hydroxy-5-en-metabolites, delta 5-3 beta-ol and delta 5-3 beta,12 alpha-ol were found as major components in the urine of patients with liver diseases (cholestasis, liver cirrhosis, chronic hepatitis, acute hepatitis). Other 3 beta-dihydroxy-5-en-metabolites, delta 5-3 beta,7 alpha-ol and delta 5-3 beta,7 beta-ol, were found as minor components in the urine. The levels of delta 5-3 beta-ol and delta 5-3 beta,12 alpha-ol in urine were correlated with their levels in serum, with total bile acids in the urine, and with liver function, implying that the degree of their increment correlated well with the severity of liver diseases. The most abundant amounts of delta 5-3 beta-ol and delta 5-3 beta,12 alpha-ol were found in the urine as sulfate conjugates in comparison with bile, portal and hepatic venous sera, and liver tissue of the patients. The biliary excretion and hepatic extraction of these 3 beta-hydroxy-5-en-unsaturated bile acids were more impaired and inefficient than those of cholic and chenodeoxycholic acids.     

Structural determinants of monohydroxylated bile acids to activate beta 1 subunit-containing BK channels

Lithocholate (LC) (10-300 microM) in physiological solution is sensed by vascular myocyte large conductance, calcium- and voltage-gated potassium (BK) channel beta(1) accessory subunits, leading to channel activation and arterial dilation. However, the structural features in steroid and target that determine LC action are unknown. We tested LC and close analogs on BK channel (pore-forming cbv1+beta(1) subunits) activity using the product of the number of functional ion channels in the membrane patch (N) and the open channel probability (Po). LC (5beta-cholanic acid-3alpha-ol), 5alpha-cholanic acid-3alpha-ol, and 5beta-cholanic acid-3beta-ol increased NPo (EC(50) approximately 45 microM). At maximal increase in NPo, LC increased NPo by 180%, whereas 5alpha-cholanic acid-3alpha-ol and 5beta-cholanic acid-3beta-ol raised NPo by 40%. Thus, the alpha-hydroxyl and the cis A-B ring junction are both required for robust channel potentiation. Lacking both features, 5alpha-cholanic acid-3beta-ol and 5-cholenic acid-3beta-ol were inactive. Three-dimensional structures show that only LC displays a bean shape with clear-cut convex and concave hemispheres; 5alpha-cholanic acid-3alpha-ol and 5beta-cholanic acid-3beta-ol partially matched LC shape, and 5alpha-cholanic acid-3beta-ol and 5-cholenic acid-3beta-ol did not. Increasing polarity in steroid rings (5beta-cholanic acid-3alpha-sulfate) or reducing polarity in lateral chain (5beta-cholanic acid 3alpha-ol methyl ester) rendered poorly active compounds, consistent with steroid insertion between beta(1) and bilayer lipids, with the steroid-charged tail near the aqueous phase. Molecular dynamics identified two regions in beta(1) transmembrane domain 2 that meet unique requirements for bonding with the LC concave hemisphere, where the steroid functional groups are located.     

Chemoselective reduction of 1,4,6-cholestatrien-3-one and 1,4,6-androstatriene-3,17-dione by various hydride reagents

The chemoselectivity of rigid cyclic alpha,beta-unsaturated carbonyl group on the reducing agents was influenced by the ring size and steric factor. Cholesterol (cholest-5-en-3beta-ol) and dehydroepiandrosterone (DHEA) were oxidized with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone to form 1,4,6-cholestatrien-3-one and 1,4,6-androstatriene-3,17-dione. They were reduced with NaBH(4), lithium tri-sec-butylborohydride (l-Selectride), LiAlH(4), 9-borabicyclo[3.3.1]nonane (9-BBN), lithium triethylborohydride (Super-hydride), and BH(3) x (CH(3))(2)S in various conditions, respectively. Reduction of 1,4,6-cholestatrien-3-one and 1,4,6-androstatriene-3,17-dione by NaBH(4) (4 equiv.) produced 4,6-cholestadien-3beta-ol and 4,6-androstadiene-3beta,17beta-diol, respectively. Reduction by l-Selectride (12 equiv.) afforded 4,6-cholestadien-3alpha-ol and 4,6-androstadiene-3alpha,17beta-diol, chemoselectively. Reaction with Super-hydride (12 equiv.) produced 4,6-cholestadien-3-one and 3-oxo-4,6-androstadien-17beta-ol. Reduction of 1,4,6-cholestatrien-3-one by 9-BBN (14 equiv.) produced 1,4,6-cholestatrien-3alpha-ol, but 1,4,6-androstatriene-3,17-dione was not reacted with 9-BBN in the reaction conditions. Reaction of LiAlH(4) (6 equiv.) formed 4,6-cholestadien-3beta-ol and 3-oxo-1,4,6-androstatrien-17beta-ol. Reduction of 1,4,6-cholestatrien-3-one by BH(3) x (CH(3))(2)S (11 equiv.) gave cholestane as major compound and unlike reactivity of cholesterol, 1,4,6-androstatriene-3,17-dione by 8 equiv. of BH(3) x (CH(3))(2)S formed 3-oxo-1,4,6-androstatrien-17beta-ol. LiAlH(4) and BH(3) x (CH(3))(2)S showed relatively low chemoselectivity.     

Simultaneous quantification of several cholesterol autoxidation and monohydroxylation products by isotope-dilution mass spectrometry

An assay based on isotope-dilution mass spectrometry with deuterium-labeled internal standards was developed for simultaneous quantification of cholest-5-ene-3 beta,7 alpha-diol (7 alpha-hydroxycholesterol), cholest-5 beta,6 beta-epoxy-3 beta-ol (cholesterol-5 beta,6 beta-epoxide), cholest-5 alpha,6 alpha-epoxy-3 beta-ol (cholesterol-5 alpha,6 alpha-epoxide), cholest-5-en-7-one-3 beta-ol (7-oxocholesterol), cholestane-3 beta,5 alpha,6 beta-triol, cholest-5-ene-3 beta,25-diol (25-hydroxycholesterol), and cholest-5-ene-3 beta,26-diol (26-hydroxycholesterol) in one single serum sample. Recovery experiments and replicate analyses showed that the assay was sufficiently sensitive, accurate, and precise. The concentrations of the listed compounds in sera from 19 healthy subjects were determined and are presented.     

Mode of formation of cholesta-5,7-dien-3β-ol from cholest-5-en-3β-ol by larvae of Calliphora erythrocephala

1. The conversion of cholest-5-en-3beta-ol (cholesterol) into cholesta-5,7-dien-3beta-ol by axenic Calliphora erythrocephala larvae was demonstrated. 2. The transformation is probably direct (Delta(5)-->Delta(5,7)) and does not involve a Delta(0) intermediate (Delta(5)-->Delta(0)-->Delta(7)--> Delta(5,7)). 3. Delta(7)-bond formation involves the stereospecific elimination of the 7beta hydrogen atom. 4. The relative amounts of free and esterified sterols were determined in larvae grown on cholesterol as sole sterol source and on 5alpha-cholestan-3beta-ol supplemented with minimal amounts of cholesterol. 5. The significance of the results is assessed in relation to the probable role of cholesta-5,7-dien-3beta-ol as an intermediate in the biosynthesis of ecdysones.     

The sterols of the echinoderm Asterias rubens

1. Twenty-two sterols were identified in the starfish Asterias rubens (Phylum, Echinodermata; Class, Asteroidea). 2. The major 4-demethyl sterols had a Delta(7) bond and the C(27) compound 5alpha-cholest-7-en-3beta-ol predominated over other mono- and di-unsaturated sterols belonging to the C(26), C(27), C(28) and C(29) series. 3. Small amounts of cholest-5-en-3beta-ol and 5alpha-cholestan-3beta-ol were also present. 4. The minor sterols identified all contained either one or two methyl groups at C-4 and are considered to be potential biosynthetic precursors of 5alpha-cholest-7-en-3beta-ol. 5. Three sterols possessing a 9beta,19-cyclopropane ring were also isolated and were probably derived by the starfish from a dietary source.     

Formation of 5,16-androstadien-3 beta-ol from pregnenolone in human testicular microsomes

A microsomal fraction of testicular tissue from a patient with prostatic carcinoma was incubated with [4-14C]pregnenolone in the presence of an NADPH-generating system for different periods of time. The metabolites were separated by Sephadex LH-20 column chromatography and then identified by thin-layer chromatography, radio-gas chromatography, and crystallization studies. Pregnenolone was converted to a major metabolite, 5-androstene-3 beta,17 beta-diol via 17-hydroxypregnenolone and then dehydroepiandrosterone. Another major metabolite was 5,16-androstadien-3 beta-ol, which increased with the time of incubation and accumulated in the incubation medium. After 120 min of incubation, 34.6% of the precursor was converted to 5-androstene-3 beta,17 beta-diol and 15.1% to 5,16-androstadien-3 beta-ol. In addition to the above-mentioned steroids, 16 alpha-hydroxypregnenolone, 5-pregnene-3 beta,20 alpha-diol, and 5-androstene-3 beta,17 alpha-diol were identified as minor metabolites of pregnenolone. From these results it was concluded that human testicular microsomes possess enzymic activities for the synthesis of 5,16-androstadien-3 beta-ol, as well as androgens from pregnenolone.     

Synthesis of iodine-131 labeled 6 beta-iodomethyl-19-norsitost-5(10)-en-3 beta-ol and 19-iodositost-5-en-3 beta-ol for adrenal imaging.

6 BETA-Iodomethyl-19-norsitost-5(10)-en-3 beta-ol (V) was synthesized by homoallylic rearrangement of 19-iodositost-5-en-3 beta-ol (IV), which was obtained by the hydrolysis of 19-iodositost-5-en-3 beta-ol acetate (III) derived from the displacement of sitost-5-ene-3 beta, 19-diol 3-acetate 19-p-toluenesulfonate (I) with sodium iodide in isopropanol. The radioiodinated IV and V were prepared by isotope exchange with sodium iodide-I-131.     

Hydroboration of 5 alpha-ergost-8-en-3 beta-ol

Hydration via hydroboration of 5 alpha-ergost-8-en-3 beta-ol affords 5 alpha-ergostane-3 beta, 15 alpha-diol, 5 alpha, 14 beta-ergostane-3 beta, 15 beta-diol, and 5 alpha-ergostane-3 beta, 7 beta-diol, and not 5 alpha, 9 beta-ergostane-3 beta, 7 beta-diol, as previously reported by others.     

Biotransformation XLVII: transformations of 5-ene steroids in Fusarium culmorum culture

The course of the transformation of six 5-ene steroids with varying substituents at C-17 or/and C-3: dehydroepiandrosterone (DHEA), 5-androsten-3beta,17beta-diol, 17alpha-methyl-5-androsten-3beta,17beta-diol, 5-androsten-17-one, 5-androsten-3beta-ol and pregnenolone by Fusarium culmorum was investigated. Three substrates with oxygen functions at C-3 and C-17 i.e. DHEA, 5-androsten-3beta,17beta-diol and 17alpha-methyl-5-androsten-3beta,17beta-diol were hydroxylated entirely at 7alpha-axial, allylic position. The mixture of 7alpha-hydroxy- and 7alpha,15alpha-dihydroxyderivatives was formed during the transformation of pregnenolone and 5-androsten-17-one, from the latter 2alpha,7alpha-dihydroxyderivative was also obtained. 7alpha,15alpha- Dihydroxyderivative was the only product isolated from the 5-androsten-3beta-ol post-transformation mixture. The time-course of the DHEA transformation by F. culmorum shows that the substrate induces 7alpha-hydroxylase activity. DHEA was transformed by androstenedione induced F. culmorum cultures to a larger extent than by a noninduced microorganism; the selectivity of the transformation remained unchanged.     

Accumulation of 14 alpha-methylergosta-8,24(28)-dien-3 beta,6 alpha-diol in 14 alpha-demethylation mutants of Candida albicans: genetic evidence for the involvement of 5-desaturase

14 alpha-Demethylation mutants of the fungus Candida albicans have been shown to accumulate 14 alpha-methylergosta-8,24(28)-dien-3 beta,6 alpha-diol. A derivative from one of these mutants (KD4900) that does not form this 6 alpha-hydroxylated sterol but is still defective in 14 alpha-demethylation (KD4950) was obtained. Mutational restitution of 14 alpha-demethylation capacity to this derivative resulted in the formation of the 5,6-saturated sterol ergosta-7,22-dien-3 beta-ol as the major product, clearly indicating that 5-desaturase deficiency exists in this demethylation-proficient revertant (KD4952). This implies that its parent, KD4950, which has lost the ability to form the hydroxylated sterol, also is deficient in 5-desaturation. We infer from the results that 5-desaturase is responsible for the formation of the hydroxylated sterol. However, it is unclear whether the hydroxylation represents a genuine step of the normal 5-desaturation reaction.     

Taraxastane-type triterpenoids from Saussurea petrovii.

Two taraxastane triterpenoids, i.e. taraxast-20-ene-3beta,30-diol (1) and 20alpha,21alpha-epoxy-taraxastane-3beta,22alpha-diol (2), as well as four known triterpenes taraxast-20(30)ene-3beta,21alpha-diol (3), taraxast-20(30)-ene-3beta-ol (4), taraxast-20-ene-3beta-ol (5) and taraxastane-3beta,20alpha-diol (6) were isolated from the Chinese medicinal plant Saussurea petrovii. Their structures were elucidated by spectroscopic methods. These compounds, especially 1 and 2, exhibit significant antitumor and antibacterial activity.     

Correlation between serum levels of some cholesterol precursors and activity of HMG-CoA reductase in human liver

The possibility that the serum concentrations of various cholesterol precursors may reflect the activity of the hepatic HMG-CoA reductase was investigated in humans under different conditions. The serum levels of squalene, free and esterified lanosterol, (4 alpha, 4 beta, 14 alpha-trimethyl-5 alpha-cholest-8, 24-dien-3 beta-ol), two dimethylsterols (4 alpha, 4 beta-dimethyl-5 beta-cholest-8-en-3 beta-ol and 4 alpha, 4 beta-dimethyl-5 alpha-cholest-8, 24-dien-3 beta-ol), two methostenols (4 alpha-methyl-5 alpha-cholest-7-en-3 beta-ol and 4 alpha-methyl-5 alpha-cholest-8-en-3 beta-ol), two lathosterols (5 alpha-cholest-7-en-3 beta-ol and 5 alpha-cholest-8-en-3 beta-ol) and desmosterol (cholest-5, 24-dien-3 beta-ol) were measured in untreated patients (n = 7) and patients treated with cholestyramine (QuestranR, 8 g twice daily for 2-3 weeks, n = 5) or chenodeoxycholic acid (15 mg/kg body weight daily for 3-4 weeks, n = 8) prior to elective cholecystectomy. The activity of the hepatic microsomal HMG-CoA reductase was measured in liver biopsies taken in connection with the operation.(ABSTRACT TRUNCATED AT 250 WORDS)