Cholesterol 7 alpha-hydroxylase

Cholesterol 7 alpha-hydroxylase, also known as cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1) is the rate-limiting enzyme in the synthesis of bile acid from cholesterol via the classic pathway, catalyzing the formation of 7α-hydroxycholesterol. In humans, it is encoded by the CYP7A1 gene. It is a cytochrome P450 enzyme, which belongs to the oxidoreductase class, and converts cholesterol to 7-alpha-hydroxycholesterol, the first and rate limiting step in bile acid synthesis.

The inhibition of cholesterol 7-alpha-hydroxylase (CYP7A1) represses bile acid biosynthesis.

Evolution

Sequence comparisons indicated a huge similarity between cytochromes P450 identified in man and bacteria, and suggested that the superfamily cytochrome P450 first originated from a common ancestral gene some three billion years ago.

The superfamily cytochrome P450 was named in 1961, because of the 450-nm spectral peak pigment that cytochrome P450 has when reduced and bound to carbon monoxide. In the early 1960s, P450 was thought to be one enzyme, and by the mid-1960s it was associated with drug and steroid metabolism.

However, the membrane-associated and hydrophobic nature of the enzyme system impeded purification, and the number of proteins involved could not be accurately counted. Advances in mRNA purification in the early 1980s allowed to isolate the first cDNA encoding a complete cytochrome P450 (CYP) protein, and thereafter, results of many cloning studies have revealed a large number of different enzymes.

Advances in molecular biology and genomics facilitated the biochemical characterisation of individual P450 enzymes:

The cytochromes P450 act on many endogenous substrates, introducing oxidative, peroxidative, and reductive changes into small molecules of widely different chemical structures.