Cholesterol 7α Hydroxylase - Catalysis

What is Cholesterol 7α Hydroxylase?

Cholesterol 7α hydroxylase is a crucial enzyme in the biosynthesis of bile acids from cholesterol. It catalyzes the hydroxylation of cholesterol at the 7α position, which is the rate-limiting step in the conversion process. This enzyme is encoded by the CYP7A1 gene and is primarily found in the liver.

Why is Cholesterol 7α Hydroxylase Important?

The enzyme plays a vital role in maintaining cholesterol homeostasis and lipid metabolism. By converting cholesterol into bile acids, it helps in the emulsification and absorption of dietary fats. Dysregulation of this enzyme can lead to cholesterol-related disorders such as gallstones and atherosclerosis.

Mechanism of Catalysis

Cholesterol 7α hydroxylase is a member of the cytochrome P450 family of enzymes. It utilizes molecular oxygen (O2) and NADPH as cofactors to introduce a hydroxyl group at the 7α position of cholesterol. The catalytic cycle involves the formation of a highly reactive iron-oxo species that facilitates the hydroxylation reaction.

Regulation of Cholesterol 7α Hydroxylase

The activity of cholesterol 7α hydroxylase is tightly regulated by various factors. These include dietary intake, hormonal control, and feedback inhibition by bile acids. For instance, high levels of bile acids in the liver can downregulate the expression of the CYP7A1 gene to prevent excess bile acid production.

Clinical Implications

Mutations or deficiencies in cholesterol 7α hydroxylase can lead to a range of metabolic disorders. Understanding the enzyme's catalytic mechanism and regulation can offer insights into therapeutic targets for treating conditions like hypercholesterolemia and non-alcoholic fatty liver disease (NAFLD).

Research and Future Directions

Ongoing research aims to elucidate the detailed structure-function relationship of cholesterol 7α hydroxylase. Advanced techniques such as cryo-electron microscopy and X-ray crystallography are being employed to obtain high-resolution structures of the enzyme. These studies can pave the way for the development of specific inhibitors or activators to modulate its activity.

Relevant Publications

Expression of hepatic genes involved in bile acid metabolism in dairy cows with fatty liver.

Issue Release: 2024

Ginsenosides retard atherogenesis via remodelling host-microbiome metabolic homeostasis.

Issue Release: 2024

Mechanism of Tianma-Gouteng granules lowering blood pressure based on the bile acid-regulated Farnesoid X Receptor-Fibroblast Growth Factor 15- Cholesterol 7α-hydroxylase pathway.

Issue Release: 2024

Aromatic Amino Acids Promote Lipid Metabolism Disorders by Increasing Hepatic Bile Acid Synthesis.

Issue Release: 2024

Free fatty acids induce bile acids overproduction and oxidative damage of bovine hepatocytes via inhibiting FXR/SHP signaling.

Issue Release: 2024

Involvement of Bile Acid Metabolism and Gut Microbiota in the Amelioration of Experimental Metabolism-Associated Fatty Liver Disease by Nobiletin.

Issue Release: 2024

Prevention of high-fat-diet-induced obesity in mice by soluble dietary fiber from fermented and unfermented millet bran.

Issue Release: 2024

A Mixture of HY7601 and KY1032 Regulates Energy Metabolism in Adipose Tissue and Improves Cholesterol Disposal in High-Fat-Diet-Fed Mice.

Issue Release: 2024

Lingguizhugan oral solution alleviates MASLD by regulating bile acids metabolism and the gut microbiota through activating FXR/TGR5 signaling pathways.

Issue Release: 2024

Cholesterol lowering in diet-induced hypercholesterolemic mice using bile salt hydrolases with different substrate specificities.

Issue Release: 2024

Liver-specific Lxr inhibition represses reverse cholesterol transport in cholesterol-fed mice.

Issue Release: 2024

The Supplementation of Berberine in High-Carbohydrate Diets Improves Glucose Metabolism of Tilapia () via Transcriptome, Bile Acid Synthesis Gene Expression and Intestinal Flora.

Issue Release: 2024

Isoastragaloside I attenuates cholestatic liver diseases by ameliorating liver injury, regulating bile acid metabolism and restoring intestinal barrier.

Issue Release: 2024

Tauroursodeoxycholic Acid Improves Nonalcoholic Fatty Liver Disease by Regulating Gut Microbiota and Bile Acid Metabolism.

Issue Release: 2024

Lysimachia christinae polysaccharide attenuates diet-induced hyperlipidemia via modulating gut microbes-mediated FXR-FGF15 signaling pathway.

Issue Release: 2023

Endogenous and Therapeutic 25-hydroxycholesterols May Worsen Early SARS-CoV-2 Pathogenesis in Mice.

Issue Release: 2023

Gardenia Iridoid Glucosides Protect Against α-Naphthalene Isothiocya-Nate-Induced Cholestatic Rats Through Activation of the FXR-SHP Signaling Pathway.

Issue Release: 2023

Astragalus saponins protect against extrahepatic and intrahepatic cholestatic liver fibrosis models by activation of farnesoid X receptor.

Issue Release: 2023

Restraint stress promotes nonalcoholic steatohepatitis by regulating the farnesoid X receptor/NLRP3 signaling pathway.

Issue Release: 2023

Influence of ursodeoxycholic acid on blood glucose, insulin and GLP-1 in rats with liver fibrosis induced by bile duct ligation.

Issue Release: 2023

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