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

Abstract

Patients suffering from cerebrotendinous xanthomatosis, an inborn error of metabolism in bile acid synthesis, excrete excessive amounts of 23-hydroxylated bile alcohols, 23-norcholic acid and 23-hydroxycholic acid into urine. In this study the configuration of this excreted 23-hydroxycholic acid was established as (23R)-hydroxycholic acid. Urine samples of two treated patients, receiving chenodeoxycholic acid, were investigated to see whether this administered bile acid was partly converted into 23-hydroxychenodeoxycholic acid. One patient was treated with ursodeoxycholic acid for 1 month and subsequently with chenodeoxycholic acid, and the urinary excretion of both (23R)-hydroxychenodeoxycholic acid and (23R)-hydroxyursodeoxycholic acid were followed. Indeed, all three patients excreted (23R)-hydroxylated chenodeoxycholic acid during oral treatment with chenodeoxycholic acid, and the patient treated with ursodeoxycholic acid excreted (23R)-hydroxylated ursodeoxycholic acid. During treatment with chenodeoxycholic acid the excretion of (23R)-hydroxychenodeoxycholic acid increases at first and later on decreases markedly. These findings suggest increased (23R)-hydroxylase activity in patients suffering from cerebrotendinous xanthomatosis, acting both on endogenously synthesized bile alcohols and on exogenously administered bile acids; during continuation of chenodeoxycholic acid treatment in an effective dose (750 mg/day) this enzyme activity gradually disappears.

• Authors: B J Koopman, B G Wolthers, J C Van der Molen, G T Nagel, H Rutgers, B Strijtveen, B Kaptein
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 883 Issue 3 Pg. 585-92 (Oct 01 1986) ISSN: 0006-3002 [Print] Netherlands
• PMID: 3756224 (Publication Type: Journal Article)

Chemical References

• Bile Acids and Salts
• Steroid Hydroxylases
• steroid (23R)-hydroxylase

Topics

• Adult
• Bile Acids and Salts (therapeutic use, urine)
• Female
• Gas Chromatography-Mass Spectrometry
• Humans
• Male
• Middle Aged
• Steroid Hydroxylases (metabolism)
• Xanthomatosis (drug therapy, enzymology, urine)