CYP7A1
Description
The CYP7A1 (cytochrome P450 family 7 subfamily A member 1) is a protein-coding gene located on chromosome 8.
Cholesterol 7 alpha-hydroxylase, also known as cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1), is an enzyme encoded by the CYP7A1 gene in humans and plays a crucial role in cholesterol metabolism. It belongs to the cytochrome P450 enzyme family, classified as an oxidoreductase. CYP7A1 converts cholesterol to 7-alpha-hydroxycholesterol, the initial and rate-limiting step in bile acid synthesis. Inhibition of CYP7A1 suppresses bile acid biosynthesis. The cytochrome P450 superfamily originated from a common ancestral gene approximately three billion years ago, as evidenced by significant sequence similarity between cytochromes P450 found in humans and bacteria. The superfamily was named in 1961 due to the 450-nm spectral peak pigment exhibited by cytochrome P450 when reduced and bound to carbon monoxide. Initially, in the early 1960s, P450 was considered a single enzyme, and by the mid-1960s, it was linked to drug and steroid metabolism. However, the membrane-associated and hydrophobic nature of the enzyme system hindered purification, making it difficult to accurately determine the number of proteins involved. Advancements in mRNA purification in the early 1980s enabled the isolation of the first cDNA encoding a complete cytochrome P450 (CYP) protein. Subsequent cloning studies revealed a large number of distinct enzymes. Progress in molecular biology and genomics facilitated the biochemical characterization of individual P450 enzymes. Cytochromes P450 act on numerous endogenous substrates, introducing oxidative, peroxidative, and reductive changes into small molecules with diverse chemical structures. Identified substrates include saturated and unsaturated fatty acids, eicosanoids, sterols and steroids, bile acids, vitamin D3 derivatives, retinoids, and uroporphyrinogens.
CYP7A1 is a cytochrome P450 monooxygenase involved in the metabolism of endogenous cholesterol and its oxygenated derivatives (oxysterols). It uses molecular oxygen, inserting one oxygen atom into a substrate and reducing the second into a water molecule. Two electrons are provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase). CYP7A1 is a critical regulatory enzyme of bile acid biosynthesis and cholesterol homeostasis. It catalyzes the hydroxylation of the carbon-hydrogen bond at the 7-alpha position of cholesterol, a rate-limiting step in cholesterol catabolism and bile acid biosynthesis. CYP7A1 also 7-alpha hydroxylates several oxysterols, including 4beta-hydroxycholesterol and 24-hydroxycholesterol. It catalyzes the oxidation of the 7,8 double bond of 7-dehydrocholesterol and lathosterol with direct and predominant formation of the 7-keto derivatives.
CYP7A1 is also known as CP7A, CYP7, CYPVII.
