Increased (23R)-hydroxylase activity in patients suffering from cerebrotendinous xanthomatosis, resulting in (23R)-hydroxylation of bile acids.

  title={Increased (23R)-hydroxylase activity in patients suffering from cerebrotendinous xanthomatosis, resulting in (23R)-hydroxylation of bile acids.},
  author={B. J. Koopman and B. G. Wolthers and Jan C. van der Molen and Gijs T. Nagel and H M Rutgers and Bert Strijtveen and Bernard Kaptein},
  journal={Biochimica et biophysica acta},
  volume={883 3},
12 Citations

The major metabolites of ursodeoxycholic acid in human urine are conjugated with N‐acetylglucosamine

The study shows that N‐acetylglucosaminides are major urinary metabolites of ursodeoxycholic acid and that the selective N‐estate‐induced dissociation of the pseudomolecular anions generated by fast atom bombardment ionization of samples from pooled urine collected from the healthy subjects during administration of urinary bile acids and from the patient given [24‐13C].

Cerebrotendinous xanthomatosis: A review of biochemical findings of the patient population in the netherlands

A relatively simple screening test for cerebrotendinous xanthomatosis was developed based on an enzymatic assay of 7α-hydroxylated steroids in urine, which allows the screening of large populations for the existence of the disease at an earlier stage of life.

Synthesis of 24-nor-5 beta-cholan-23-oic acid derivatives: a convenient and efficient one-carbon degradation of the side chain of natural bile acids.

The procedure provides a more rapid alternative to the Barbier-Wieland degradation for shortening by one methylene group the side chain of natural (C24) bile acids.

Altered bile acid metabolism in liver disease: concurrent occurrence of C-1 and C-6 hydroxylated bile acid metabolites and their preferential excretion into urine.

It is suggested that hepatic 1 beta- or 6 alpha-hydroxylation of bile acids occurred concurrently in the patients with liver disease and that the resulting hydroxylated metabolites were efficiently excreted in the nonsulfate-nonglucuronide form into urine rather than into bile.

Studies on naproxen/non-steroidal anti-inflammatory drug treatment: influence of disease activity of rheumatoid arthritis and patient age

In patients, concentrations of the drug not bound by prQtein, were higher, resulting in a larger area under the concentration-time curve, than in volunteers, and clearance of unbound drug and volume of distribution were smaller in patients.

Capillary gas-liquid chromatographic separation of bile alcohols.

Bile alcohols with two ring hydroxyl groups at 3 alpha- and 7 alpha-positions consistently showed larger retention times on CP-Sil-19 CB columns and smaller retention times at CP- Sil-5 CB columns than the corresponding bilecohols with three ring hydoxyl groups.



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

This hypothesis that the basic metabolic defect in the rare inherited disease cerebrotendinous xanthomatosis (CTX) is a lack of a hepatic mitochondrial C27-steroid 26-hydroxylase, involved in the normal biosynthesis of bile acids is suggested and tested in vivo.

Biosynthesis of bile acids in cerebrotendinous xanthomatosis. Relationship of bile acid pool sizes and synthesis rates to hydroxylations at C-12, C-25, and C-26.

Results demonstrate severely depressed primary bile acid synthesis in cerebrotendinous xanthomatosis with a reduction in chenodeoxycholic acid formation and pool size disproportionately greater than that for cholic acid.

Bile acid therapies applied to patients suffering from cerebrotendinous xanthomatosis.

Cerebrotendinous xanthomatosis: a defect in mitochondrial 26-hydroxylation required for normal biosynthesis of cholic acid.

It is concluded that the major pathway in the biosynthesis of cholic acid in human liver involves a mitochondrial C27-steroid 26-hydroxylation.

Absolute configuration of pentahydroxy bile alcohols excreted by patients with cerebrotendinous xanthomatosis: a circular dichroism study.

The absolute configurations of the C27 pentahydroxy bile alcohols present in bile and feces of two patients with cerebrotendinous xanthomatosis (CTX) were determined by circular dichroism (CD) spectroscopy to establish a structural mechanism for the conversion of 5beta-cholestane-3alpha,7alpha,12alpha,24S,25-pentol into cholic acid in man as well as in animals.

Bile alcohol metabolism in man. Conversion of 5beta-cholestane-3alpha, 7alpha,12alpha, 25-tetrol to cholic acid.

Results suggest that 5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol may be a precursor of cholic acid in man, and the possibility that C26-hydroxy intermediates represent the normal pathway can not be excluded.

Biosynthesis of bile acids in man. Hydroxylation of the C27-steroid side chain.

The results indicate that microsomal 26-hydroxylation is less important than mitochondrial 26-Hydroxylating system under normal conditions, and the possibility thatmicrosomal 25-hydroxy-4-cholesten-3-one is important cannot be ruled out.

Assay of intermediates in bile acid biosynthesis using isotope dilution--mass spectrometry: hepatic levels in the normal state and in cerebrotendinous xanthomatosis.

In a liver sample from a patient with cerebrotendinous xanthomatosis (CTX), the amounts of the 12 alpha-hydroxylated steroids were considerably higher than in the normal liver, in accordance with the previous demonstration that the basic metabolic defect in CTX is a lack of the mitochondrial 26-Hydroxylase.