Abstract
Di- and trihydroxycoprostanoic acid (D-, THCA), normal intermediates of bile acid synthesis in man, are usually undetectable in normal serum. Very high levels however are found in the serum of patients with Zellweger Syndrome (ZS), an entity in which the absence of morphologically distinquishable peroxisomes can be considered as the most conspicous finding. To explain the accumulation of D- and THCA, C27-bile acids with an incompletely oxidized side chain, we studied the side chain cleavage activity from cholesterol to primary bile acids in liver homogenates from controls and ZS-patients. The results presented indicate a strongly reduced cholesterol side chain cleavage activity in the liver from ZS patients (n=3) ranging from 9-14% of the activity in normal controls.
The findings that in experimental animals clofibrate stimulates both bile acid formation and fatty acid β-oxidation, together with the reported deficiency of all fatty acid β-oxidation enzymes in ZS and the impaired chain shortening of fatty- and bile acids suggest that the same set of enzymes is involved in the β-oxidation of longchain fatty acids and C27-bile acids. These findings in ZS patients lacking peroxisomes not only provide an explanation for the D- and THCA accumulation in the serum, but it also suggests that peroxisomes are involved in bile acid metabolism in man and especially in the side chain cleavage process. This conclusion is supported by recent findings in the rat.
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Heymans, H., Wanders, R. & Schutgens, R. 76 IMPAIRED CHOLESTEROL SIDE CHAIN CLEAVAGE IN PATIENTS WITHOUT PEROXISOMES (ZELLWEGER SYNDROME). Pediatr Res 20, 1046 (1986). https://doi.org/10.1203/00006450-198610000-00130
Issue Date:
DOI: https://doi.org/10.1203/00006450-198610000-00130