The formation and metabolism of 3α,7α-dihydroxy-5β-cholestan-26-oic acid in man

Hanson, Russell F.

doi:10.1172/jci106698

Cited by 30 publications

(13 citation statements)

References 11 publications

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“…When the area under the sp act curve of [3H]chenodeoxycholic acid (derived from precursor) was divided by the area under the sp act curve of the [14C]chenodeoxycholic acid (17), the conversion of [3H]DHCA into [3H]chenodeoxycholic acid was calculated to be only 2%. In a similar study, an 80% conversion of DHCA into chenodeoxycholic acid after 12 h was found in an adult with bile fistula (20).…”

Section: Serum Bile Acids the Clinical Diagnosis Of Zellweger Syndromesupporting

confidence: 57%

“…Kase acid. In contrastythe patient with a bile fistula incorporated only 2% of the tritium activity from administered [3H]DHCA into cholic acid (20). In the metabolic defect found in our patient, the cholic acid formation pathway is relatively more important, allowing an increased excretion of toxic metabolites (25, 26).…”

Section: Discussionmentioning

confidence: 68%

“…As time passed, only a minor part of the tritium in the administered ['HIDHCA was incorporated into chenodeoxycholic acid. In addition, the course of incorporation was very slow, only about 3% after 12 h. This finding is in contrast to the 80% conversion of DHCA into chenodeoxycholic acid after 12 h in an adult with bile fistula (20). The very low pool size of chenodeoxycholic acid, calculated from the sp act decay curve of biliary ['4C]chenodeoxycholic acid, supports the low formation of chenodeoxycholic acid.…”

Section: Discussionmentioning

confidence: 79%

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Importance of Peroxisomes in the Formation of Chenodeoxycholic Acid in Human Liver. Metabolism of 3α,7α-Dihydroxy-5β-cholestanoic Acid in Zellweger Syndrome

et al. 1991

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ABSTRACT. Infantile Zellweger syndrome belongs to the group of peroxisomal disorders that lack peroxisomes. Both trihydroxycoprostanic acid (THCA), the precursor to cholic acid, and dihydroxycoprostanic acid (DHCA), the precursor to chenodeoxycholic acid, accumulate in this disease. In previous studies, we have shown that liver peroxisomes are required for the conversion of THCA into cholic acid both in vitro and in vivo by measuring a defective conversion in infants with Zellweger syndrome. In our present study, the conversion of DHCA into chenodeoxycholic acid has been measured in an infant with Zellweger syndrome to evaluate the importance of liver peroxisomes for the formation of chenodeoxycholic acid. Coprostanic acidemia was present from the second day of life with high levels of THCA and only trace amounts of DHCA. The conversion of i.v. administered 13H]DHCA into chenodeoxycholic acid was only 7% compared with the 80% conversion in an analogous study in an adult. There was, however, a rapid incorporation of 'H into biliary THCA and, after a lag phase, the 3H was incorporated into biliary cholic acid. After 72 h, 15% of 13H]DHCA was converted to cholic acid. The pool size of DHCA was 1.2 mg/m2 and the pool size of both cholic acid and chenodeoxycholic acid was markedly reduced. The renal excretion of cholic acid was more efficient than that of the less polar chenodeoxycholic acid. More polar metabolites of DHCA and THCA are formed in alternative metabolic pathways facilitating renal excretion of these toxic intermediates. We conclude that liver peroxisomes are essential for a normal conversion of DHCA into chenodeoxycholic acid. (Pediarr Res 29: 64-69, 1991) Abbreviations DHCA, 3a,7a-dihydroxycoprostanic acid (or 3a,7a-dihydroxy-50-cholestanoic acid) THCA, 3a,7a,l2a-trihydroxycoprostanic acid C2,-dicarboxylic acid, 3a,7a,12a-trihydroxy-27-carboxymethylcoprostanic acid GC-MS, gas chromatography-mass spectrometry

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Section: Serum Bile Acids the Clinical Diagnosis Of Zellweger Syndromesupporting

confidence: 57%

Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 79%

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Importance of Peroxisomes in the Formation of Chenodeoxycholic Acid in Human Liver. Metabolism of 3α,7α-Dihydroxy-5β-cholestanoic Acid in Zellweger Syndrome

et al. 1991

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“…Thus, the conversion of 3H-labeled 26-hydroxylated precursors into cholic acid + chenodeoxycholic acid was efficient in the CTX-patients as well as in the control subjects. In particular, the recovery in bile as chenodeoxycholic acid of the 3H-labeled 26-hydroxylated precursors was about the (23)(24)(25). In view of this, the ratio between 14C-and 3H-activity (from the non-26-hydroxylated and the 26-hydroxylated precursor respectively) recovered in cholic acid and chenodeoxycholic acid C'/I/T 0.004 formed in the control subjects is not likely to be changed with time.…”

Section: Discussionmentioning

confidence: 99%

Role of the 26-hydroxylase in the biosynthesis of bile acids in the normal state and in cerebrotendinous xanthomatosis. An in vivo study.

Björkhem¹,

Fausa²,

Hopen³

et al. 1983

J. Clin. Invest.

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“…1 The sequence of reactions that leads to the formation of 5,8-cholestane-3a,7a-diol in man has been studied (2), but the mechanism of degradation of the side chain has not been completely established. There are indications that one mechanism of side-chain degradation in man involves 26-hydroxylation, because 3a,7a-dihydroxy-5f3-cholestanoic acid has been isolated from human bile and has been shown to be formed from cholesterol and metabolized into chenodeoxycholic acid (3 (11). The labeled substrate was purified by column and thin-layer chromatography (TLC)2 as previously described (12,13), to constant specific radioactivity (1.61 x 107 dpm/,umol; radiopurity 98.8%).…”

mentioning

confidence: 99%