Importance of Peroxisomes in the Formation of Chenodeoxycholic Acid in Human Liver. Metabolism of 3α,7α-Dihydroxy-5β-cholestanoic Acid in Zellweger Syndrome
| Autor: | Jan I. Pedersen, Bengt Frode Kase, Jan Gustafsson, Karl-Olaf Wathne, Ingemar Björkhem |
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| Rok vydání: | 1991 |
| Předmět: |
Male
medicine.medical_specialty medicine.drug_class Biology Chenodeoxycholic Acid Kidney Microbodies Cerebrohepatorenal syndrome Bile Acids and Salts chemistry.chemical_compound Internal medicine Chenodeoxycholic acid Peroxisomal disorder medicine Bile Humans Zellweger Syndrome Zellweger syndrome Bile acid Cholic acid Infant Kidney metabolism Peroxisome medicine.disease Endocrinology Liver chemistry Biochemistry Pediatrics Perinatology and Child Health Cholestanols |
| Zdroj: | Pediatric Research. 29:64-69 |
| ISSN: | 1530-0447 0031-3998 |
| DOI: | 10.1203/00006450-199101000-00013 |
| Popis: | 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 [3H]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 3H into biliary THCA and, after a lag phase, the 3H was incorporated into biliary cholic acid. After 72 h, 15% of [3H]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. |
| Databáze: | OpenAIRE |
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