A new role for cytochrome P450 3A4

 

Cytochrome P450 3A4 is an incredibly important enzyme in the human body. It's the protein that breaks down common drugs like the fever reducer and painkiller acetaminophen and the antibiotic erythromycin. Cholesterol also is broken down by the CYP3A family of enzymes and is believed to be mostly metabolized into 4β-hydroxycholesterol. In a commentary appearing in the August issue of the Journal of Lipid Research, Ulf Diczfalusy and Ingemar Björkhem discuss some new data suggesting another function for the enzyme based on end products discovered by Akira Honda and colleagues: the 25-hydroxyation of cholesterol.

Many studies have been conducted using 25-hydroxycholesterol, which is a potent regulator of lipid metabolism. However, the origins of this oxysterol have not been entirely elucidated. Honda et al.'s straightforward investigations in their article, "Cholesterol 25-hydroxylation activity of CYP3A," suggest that the presence of 25-hydroxycholesterol in human circulation may be the result of CYP3A4 activity. When the authors inhibited the enzyme, 25-hydroxycholesterol levels fell. Conversely, when they increased the amount of the enzyme present in vitro, observed cholesterol levels increased. Thus, their data strongly support the idea that CYP3A is one of the enzymes responsible for catalyzing the 25-hydroxylation of cholesterol.

Mary L. Chang (mchang@asbmb.org) is managing editor of the Journal of Lipid Research. 

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