Molecular Classification
Enzyme, Cytochrome P450 family, Monooxygenase
Other Names
Cholesterol 7α-hydroxylase, CYP7A1, Cytochrome P450 7A1, Cholesterol 7-alpha-monooxygenase
Disease Roles
Cardiovascular disease: Dysregulation can affect serum cholesterol levels and atherosclerosis riskNon-alcoholic fatty liver disease (NAFLD): CYP7A1 activity correlates with steatosis and hepatic cholesterol handlingDiabetes and obesity: CYP7A1 modulation shows protection against diet-induced obesity and insulin resistance

Cholesterol 7α-hydroxylase Overview

Cholesterol 7α-hydroxylase (CYP7A1) is a liver-specific microsomal cytochrome P450 enzyme that catalyzes the initial and rate-limiting step in the classic pathway of bile acid biosynthesis, converting cholesterol to 7α-hydroxycholesterol[7][1]. It plays a central role in maintaining cholesterol and bile acid homeostasis, affecting lipid metabolism and nutrient absorption. CYP7A1 is tightly regulated at the transcriptional and post-transcriptional levels by nuclear receptors (FXR, LXR, HNF4α, SHP, FOXO1, LRH-1) and by microRNAs such as miR-33a and miR-122a. Therapeutic modulation of CYP7A1 is explored in managing hyperlipidemia, NAFLD, obesity, and related metabolic disorders[1][2][3][6][7].

Mechanism of Action

Transcriptional repression or activation: FXR agonists suppress CYP7A1 transcription via nuclear receptor signaling. miRNA-mediated post-transcriptional regulation: miR-33a, miR-122a, and miR-422a modulate CYP7A1 mRNA stability and translation in hepatocytes. Ligand activation: Nuclear receptors (LXR, FXR, HNF4α, SHP, FOXO1, LRH-1) bind the CYP7A1 promoter and regulate activity in response to metabolites and hormones.

Biological Functions

Bile acid biosynthesis: Initiates bile acid synthesis by converting cholesterol to 7α-hydroxycholesterol
Cholesterol homeostasis: Regulates cholesterol catabolism in hepatocytes
Regulation of lipid metabolism: Impacts hepatic fatty acid and cholesterol synthesis and absorption
Detoxification and hormone metabolism: As typical of P450 enzymes

Disease Associations

Cardiovascular disease: Dysregulation can affect serum cholesterol levels and atherosclerosis risk
Non-alcoholic fatty liver disease (NAFLD): CYP7A1 activity correlates with steatosis and hepatic cholesterol handling
Diabetes and obesity: CYP7A1 modulation shows protection against diet-induced obesity and insulin resistance
Other metabolic diseases: Disorders related to bile acid and lipid metabolism

Safety Considerations

  • Risk of cholestasis or hepatotoxicity if bile acid synthesis becomes dysregulated
  • Potential for altered lipid absorption and fat-soluble vitamin deficiency
  • Possible interaction with other metabolic pathways via nuclear receptor cross-talk

Interacting Drugs

Bile acid sequestrants
FXR agonists (e.g., GW4064)
Phenobarbital, pregnenolone 16α-carbonitrile, and thyroid hormone (induce CYP7A1 activity)

Associated Biomarkers

Biomarker
Serum cholesterol and triglyceride levels
Bile acid pool size and composition
Hepatic CYP7A1 mRNA or protein expression