Comparison of 12α-hydroxylation of oxygenated 5α-cholestanes and allochenodeoxycholate with rat liver microsomes

Mui, Mei Mei; Elliott, William H.

doi:10.1021/bi00683a024

Cited by 21 publications

(3 citation statements)

References 26 publications

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“…Hydroxylation in the 6aposition is particularly prominent in the pig [23], while 16~-hydroxylation is considered typical of boid snakes [24]. Hydroxylation in the 12a-position has been described for chicken [25] and with all0 bile acids in rat liver [26].…”

Section: Discussionmentioning

confidence: 99%

“…A strong correlation was found between the excretion of the sulphated unsaturated bile acids 3P-hydroxy-5-cholenoic and 3/3,12a-dihydroxy-5cholenoic acids (P < 0.001). 12a-Hydroxylation of bile acids with planar A/B ring system occurs in the rat liver [26], and this transformation might be of importance in the metabolism and elimination of 3P-hydroxy-5cholenoic acid, a compound with high liver toxicity [32, 331. Conjugation and sulphation. Nearly all patients excreted small amounts of unconjugated bile acids in urine.…”

Section: Discussionmentioning

confidence: 99%

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Bile acid profiles in urine of patients with liver diseases

Bremmelgaard

Sjövall

1979

Eur J Clin Investigation

147

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Abstract. Quantitative gas chromatography‐mass spectrometry was used to study the metabolic profiles of unconjugated, conjugated and sulphated bile acids in urine of patients with intermittent intrahepatic cholestasis of unknown aetiology, cirrhosis of the liver, primary biliary cirrhosis, viral and toxic hepatitis and extrahepatic cholestasis. A large number of bile acids was present which can broadly be classified into four groups: cholic and chenodeoxycholic acids constituted between 49·4% and 77·9% of the total bile acids (mean values of the groups); deoxycholic and other 3,12‐disubstituted bile acids between 1·3% and 12·3%, monohydroxy bile acids between 6·7% and 14·4% and bile acids hydroxylated at C‐1 or C‐6 between 4·6% and 14·6%. The high proportion of bile acids from the latter group, and the presence of tetrahydroxylated bile acids, clearly distinguished hepatic disease from the normal state. The metabolic profiles were very variable and there were few consistent differences between the groups of diseases studied. Norcholic acid constituted a significantly higher percentage of the total bile acids in cirrhotic patients (6·2 ± 6·8%) than in non‐cirrhotic patients (1·3±1·8%, P<0·001). With this exception, no profile was specific for any type of intra‐ or extra‐hepatic cholestasis. The excretion rates of the major l‐hydroxylated bile acids were positively correlated to each other. The same was true for the major 6‐hydroxylated bile acids. This may indicate that cholic, chenodeoxycholic and deoxycholic acids act as substrates for common 1‐ and 6‐hydroxylating enzymes. Possibly the taurine conjugates are preferred substrates since 1‐hydroxylated bile acids and hyocholic acid were found mainly in this fraction. A positive correlation between the excretion of sulphated 3β‐hydroxy‐5‐cholenoic acid and 3β,12α‐dihydroxy‐5‐cholenoic acid indicates a direct metabolic relationship between these compounds. Confirming previous data, a high proportion of bile acids was sulphated. The degree of sulphation increased with decreasing number of hydroxyl groups, reaching 100% for the monohydroxy and most of the dihydroxy acids. Tetrahydroxycholanoates were not sulphated, and sulphation of trihydroxycholanoates was positively correlated to the renal bile acid excretion rate. Bile from patients with intermittent intrahepatic cholestasis did not contain the tetrahydroxylated bile acids present in urine. Hyocholic acid was a very minor, mainly taurine conjugated, bile acid. Monohydroxy bile acids were usually below the detection limit. These data do not support the hypothesis that lithocholic acid participates in the initiation or perpetuation of intermittent intrahepatic cholestasis of unknown aetiology.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bile acid profiles in urine of patients with liver diseases

Bremmelgaard

Sjövall

1979

Eur J Clin Investigation

147

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“…A strong correlation was found between 313-hydroxy-5-cholenoic and 38,IZa-dihydroxy-5-cholenoic acids ( P < 0.00 I). 3P-Hydroxy-5cholenoic acid possesses a high degree of liver toxicity [40,411, and 12-hydroxylation, as shown to occur in the rat liver [42], might be instrumental in the elimination of this bile acid.…”

Section: Discussionmentioning

confidence: 99%

Urinary bile acids in late pregnancy and in recurrent cholestasis of pregnancy

Thomassen

1979

Eur J Clin Investigation

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The metabolic profiles of urinary bile acids in pregnant women in the last trimester and patients with recurrent intrahepatic cholestasis of pregnancy (RCP) were studied. Following separation according to mode of conjugation, about thirty different bile acids were quantitatively analysed by gas chromatography-mass spectrometry. In all patients the sulphate fraction comprised 50--90% of the total bile acids. In RCP a shift from glycine to taurine conjugation was noted to together with a slight relative increase in sulphation. A ten- to hundred-fold increase in cholic and chenodeoxycholic acids was seen in RCP, the increase being mainly in the sulphate fraction. Tetrahydroxylated bile acids, tentatively regarded as 1- and 6-hydroxylated products of cholic acid, were quantitatively important in patients with RCP. The relative amounts of the secondary bile acids, deoxycholic and lithocholic acids, decreased with increasing cholestasis. Metabolites hydroxylated at C-6 were common, and the excretion of hydroxylated at C-6 were common, and the excretion of hyocholic acid was positively correlated to that of chenodeoxycholic acid. An increase in the excretion of 5 alpha-configurated bile acids in RCP was noted. A positive correlation between the excretion of 3 beta-hydroxy-5-cholenoic acid and 3 beta,12 alpha-dihydroxy-5-cholenoic acid indicates a metabolic relationship between the two compounds. Because of the relatively small amounts of lithocholic and 3 beta-hydroxy-5-cholenoic acids in patients with RCP, these compounds do not seem to be of pathogenetic importance in this type of cholestasis.

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Bile acids. LXXI. A new synthesis of (25R)‐3α, 7α‐dihydroxy‐[5α,6α‐³H₂]‐5α‐cholestan‐26‐oic acid (1)

Tal

Elliott

Doisy

1985

Labelled Comp Radiopharmac

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Comparison of 12α-hydroxylation of oxygenated 5α-cholestanes and allochenodeoxycholate with rat liver microsomes

Cited by 21 publications

References 26 publications

Bile acid profiles in urine of patients with liver diseases

Bile acid profiles in urine of patients with liver diseases

Urinary bile acids in late pregnancy and in recurrent cholestasis of pregnancy

Bile acids. LXXI. A new synthesis of (25R)‐3α, 7α‐dihydroxy‐[5α,6α‐³H₂]‐5α‐cholestan‐26‐oic acid (1)

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Comparison of 12α-hydroxylation of oxygenated 5α-cholestanes and allochenodeoxycholate with rat liver microsomes

Cited by 21 publications

References 26 publications

Bile acid profiles in urine of patients with liver diseases

Bile acid profiles in urine of patients with liver diseases

Urinary bile acids in late pregnancy and in recurrent cholestasis of pregnancy

Bile acids. LXXI. A new synthesis of (25R)‐3α, 7α‐dihydroxy‐[5α,6α‐3H2]‐5α‐cholestan‐26‐oic acid (1)

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Bile acids. LXXI. A new synthesis of (25R)‐3α, 7α‐dihydroxy‐[5α,6α‐³H₂]‐5α‐cholestan‐26‐oic acid (1)