Lack of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase/isomerase in fibroblasts from a child with urinary excretion of 3 beta-hydroxy-delta 5-bile acids. A new inborn error of metabolism.

Abstract

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

The bile acid synthetic gene 3β-hydroxy-Δ5-C27-steroid oxidoreductase is mutated in progressive intrahepatic cholestasis

“…These include the CYP7B1 oxysterol 7α-hydroxylase (5), the C 27 3β-HSD (3,8), and a 3-oxo-∆ 4 -steroid 5β-reductase (4). These enzymes normally catalyze sequential steps in bile acid synthesis and, when missing, a characteristic spectrum of sterol intermediates accumulates.…”

Fetal alcohol exposure impairs hedgehog cholesterol modification and signaling

“…Ethanol causes an inhibition of HMG-CoA reductase activity, which results in decreased free cholesterol in the cells, and reduction in circulating cholesterol levels. [46][47][48] Acute ethanol exposure in perfused rat liver results in depletion of cholesterol in both liver homogenate and microsomes. 49 Ethanol specifically inhibits hepatic ACAT activity, which can lead to decreased cholesterol esters for transport in LDLs.…”

Measurement of Transport Activities of 3β-Hydroxy-Δ⁵-bile Acids in Bile Salt Export Pump and Multidrug Resistance-Associated Proteins Using LC-MS/MS

“…1, are the major bile acids excreted in the urine of patients with 3β-hydroxy-Δ 5 -C 27 -steriod dehydrogenase/isomerase (HSD3B7) deficiency. [7][8][9][10][11][12][13][14][15] Deficiency of this enzyme is thought to cause chronic liver injury in childhood. [7][8][9][10][11] The above ABC transporters may play key roles in excretion of these 3β-hydroxy-Δ 5 -bile acids from the liver.…”

“…[7][8][9][10][11][12][13][14][15] Deficiency of this enzyme is thought to cause chronic liver injury in childhood. [7][8][9][10][11] The above ABC transporters may play key roles in excretion of these 3β-hydroxy-Δ 5 -bile acids from the liver. It has also been reported that in cholestasis, up-regulation of hepatic hMRP3 is an adaptive response, providing an alternative excretory pathway to help address the overload of bile acids.…”

“…9,10,12) The GC-MS method may be applicable for measurements of transport activities of these unusual bile acids in membrane vesicles without using RI labels. However, under the alkaline or acidic conditions usually used for deconjugation in the GC-MS method, 3β-hydroxy-Δ 5 -bile acids are expected to be converted into their dehydrated products or complicated degradation products.…”