[Mechanisms of bile acid biosynthesis regulation--autoregulation by bile acids]

Bile acids play significant role in body homeostasis regulation. They are products of cholesterol catabolism and ligands for some nuclear receptors regulating crucial metabolic pathways. The main enzyme regulating bile acids biosynthesis is CYP7A1 (7alpha-cholesterol hydroxylase). Its activity is controlled mainly at the transcription level and the key transcription factor is FXR. It is activated by other nuclear receptors like SHP, HNF-4alpha or LRH-1 and bile acids themselves, and represses CYP7A1 gene. The other transcription factors that inhibit CYP7A1 activity, are PXR, VDR, PPARalpha. The main activator is LXR (in rodents), increasing CYP7A1 transcriptional activity. CYP7A1 activity increases in presence of insulin and glucocorticoids. It is also regulated by diurnal rhythm. Some of those factors influence the activities of other bile acids biosynthesis enzymes--CYP7B1, CYP27A1, CYP8B1. Because of bile acids significant function in body metabolism this article presents the newest knowledge on mechanisms of key enzymes activities control.