Studies on sterol 27-hydroxylase (CYP27A1)

摘要: Human sterol 27-hydroxylase (CYP27A1) has been studied in the present thesis with focus on substrate specificity and possible role of enzyme for prevention accumulation cholesterol cholestanol tissues. Attempts have made to evaluate a metabolic pathway bile acids human primary hepatocytes that starts 27-hydroxylation catalyzed by CYP27A1. The first Swedish case deficiency (Cerebrotendinous xanthomatosis, CTX) is described mutation CYP27A1 gene defined. Substrate Polar substrates were found be 27-hydroxylated more efficiently than unpolar recombinant or cells overexpressing A precursor cholesterol, 7dehydrocholesterol, was less efficient Cholestanol, 5αsaturated analogue at about same rate as cholesterol. Cholestenone, cholestanol, highly findings may part explanation patients (CTX). Cholestanol also leave cultured slower giving partial its selective CTX. Possible Cholesterolosis condition esters mucosa gallbladder. mRNA, protein activity both normal gall bladder cholesterolosis similar amounts. esterifying ACAT upregulated cholesterolosis, probably secondarily high levels. conclusion study does not seem pathogenic factor cholesterolosis. Levels esterified 27OH-cholesterol, product CYP27A1, markedly increased secondary effect esterification. tendons contain ratio between 27OH-cholesterol increased, suggesting mechanism operating are interest relation preferential Role step acid formation Labelled converted into cholic chenodeoxycholic considerably corresponding conversion labelled 7αOHcholesterol. latter oxysterol formed rate-limiting sterp classical from acids. starting 27OHcholesterol acid. Due variable degree different experiments, no firm conclusions could drawn respect relative 27-hydroxylation. First cholestatic infant boy who died organ failure nonsence exon 7 (G1234T, E408stop) gene, previously described. Both parents, cousins, heterozygous mutation. Together an infection cytomegalovirus, lack contributed death this patient. results studies emphasize importance consistent suggested preventing various (Photograph cover: crystal culture medium tenocytes macrophages, isolated xanthoma patient familial hypercholesterolemia. Photo author.)