Demonstration of 26-hydroxylation of C27-steroids in human skin fibroblasts, and a deficiency of this activity in cerebrotendinous xanthomatosis

The Journal of Clinical Investigation
S SkredeS M Grundy

Abstract

26-Hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol and other C27-steroids was demonstrated in cultured skin fibroblasts from healthy individuals. Activities in skin fibroblasts were approximately 5-10% of those previously found in human liver homogenates, and were inhibited by CO. The apparent Km was lowest for 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol (1.3 mumol/liter) and highest for 5-cholestene-3 beta, 7 alpha-diol (12 mumol/liter). The rate of 26-hydroxylation was highest with 7 alpha-hydroxy-4-cholesten-3-one. These characteristics are similar to those of hepatic mitochondrial C27-steroid 26-hydroxylase. In skin fibroblasts from three patients with cerebrotendinous xanthomatosis (CTX), 26-hydroxylation of C27-steroids proceeded at a rate of only 0.2-2.5% of healthy controls. No accumulation of endogenous 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol could be demonstrated in these cells, and the lowered formation of radioactive, 26-hydroxylated products could not be explained by dilution of the labeled exogenous substrate. The present results add strong evidence to the concept that the primary metabolic defect in CTX is a deficiency of C27-steroid 26-hydroxylase.

References

Apr 1, 1976·The Journal of Clinical Investigation·S SheferE H Mosbach
Oct 1, 1978·Lipids·A A Kandutsch, H W Chen
Jan 1, 1979·The Journal of Clinical Investigation·G SalenG S Tint
Mar 1, 1975·The Journal of Clinical Investigation·I BjörkhemB Persson

❮ Previous
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Citations

Apr 1, 1988·Journal of Bioenergetics and Biomembranes·H R Scholte
Jan 1, 1991·Journal of Inherited Metabolic Disease·P T Clayton
Jun 22, 1992·Biochimica Et Biophysica Acta·K NagataT Shimizu
Jul 1, 1987·Chemistry and Physics of Lipids·L L Smith
Nov 1, 1995·Atherosclerosis·K ClareM J Mitchinson
Apr 12, 2005·Clinica Chimica Acta; International Journal of Clinical Chemistry·Marina Del PuppoMarzia Galli Kienle
Mar 1, 2005·Metabolism: Clinical and Experimental·Jacob J ClarenbachKlaus von Bergmann
Feb 13, 2001·Atherosclerosis·C M ShanahanN R Cary
Jul 20, 2000·Journal of Chromatography. B, Biomedical Sciences and Applications·G HalperinD Harats
Jan 29, 2003·The Journal of Nutritional Biochemistry·Gabriella LeonarduzziGiuseppe Poli
Aug 30, 1994·Proceedings of the National Academy of Sciences of the United States of America·I BjörkhemE Lund
Oct 31, 2003·Journal of Medicinal Food·Yousuke Seyama
May 7, 2004·Proceedings of the National Academy of Sciences of the United States of America·Jeffrey B ChengDavid W Russell
Jun 10, 2008·Clinica Chimica Acta; International Journal of Clinical Chemistry·Andrea CrosignaniCarla Colombo
Jul 17, 2004·Journal of Atherosclerosis and Thrombosis·Makoto KinoshitaTamio Teramoto
May 26, 1992·Biochemistry·D W Russell, K D Setchell
Sep 20, 1997·The Journal of Biological Chemistry·M SchwarzD W Russell
Feb 1, 1996·Arteriosclerosis, Thrombosis, and Vascular Biology·E LundI Björkhem
Oct 4, 2006·Physiological Reviews·Elina Ikonen
Sep 1, 2019·International Journal of Molecular Sciences·Deborah MinzaghiSandrine Dubrac
Nov 1, 1987·Scandinavian Journal of Clinical and Laboratory Investigation·K M BobergS Skrede
Jan 1, 1994·Scandinavian Journal of Gastroenterology. Supplement·I Björkhem
Sep 1, 1988·Scandinavian Journal of Clinical and Laboratory Investigation·S SkredeS Skrede
Aug 16, 2001·The Journal of Biological Chemistry·X FuE G Lund
Jan 5, 2000·Physiological Reviews·G J Schroepfer
Feb 17, 2018·The Journal of Steroid Biochemistry and Molecular Biology·Robert C TuckeyAndrzej T Slominski
Mar 29, 2002·The Journal of Laboratory and Clinical Medicine·William C Duane, Norman B Javitt
Jul 1, 1997·Archives of Biochemistry and Biophysics·I A PikulevaM R Waterman

❮ Previous
Next ❯

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