No abstract

26-Hydroxylation of 5j6-cholestane-3a,7a,12a-triol and other C2rsteroids was demonstrated in cultured skin fibroblasts from healthy individuals. Activities in skin fibroblasts were -5-10% of those previously found in human liver homogenates, and were inhibited by CO. The apparent K., was lowest for 5,B-cholestane3a,7a,12a-triol (1.3 Mmol/liter) and highest for 5-cholestene-3(3,7a-diol (12 Mmol/liter). The rate of 26-hydroxylation was highest with 7a-hydroxy4-cholesten-3-one. These characteristics are similar to those of hepatic mitochondrial C2rsteroid 26-hydroxylase.In skin fibroblasts from three patients with cerebrotendinous xanthomatosis (CTrX), 26-hydroxylation of C2rsteroids proceeded at a rate of only 0.2-2.5% of healthy controls. No accumulation of endogenous 5,B-cholestane-3a,7a,12a-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 Cr-steroid 26-hydroxylase.

No abstract

Two Norwegian patients with chronic tyrosinemia type I

Cultured fibroblasts were shown to be capable of catalyzing the conversion of 7a-hydroxy-cholesterol to 7a-hydroxy4-cholesten-3-one, an important reaction in bile acid synthesis. The apparent K. was 7 ,umol/liter and V.,,. varied between 3 and 9 nmol/mg protein per h under the assay conditions used.The assay was used to investigate fibroblasts from a patient who presented with a familial giant cell hepatitis and who was found to excrete the monosulfates of 3,j,7a-dihydroxy-5-cholenoic acid and 3,8,7a,12a-trihydroxy-5-cholenoic acid in urine